bluuebunny/crossref_metadata_2025 huggingface dataset:
The loss of aquatic and riparian plant communities: Implications for their consumers in a riverine food web
Authors: DEEGAN BRIAN M. , GANF GEORGE G.
Published: July 2008

Abstract  Human induced alterations to rivers and steams have resulted in significant changes to the structure and diversity of riparian and aquatic plant communities. These changes will impact on the dynamics of riverine carbon cycles and food web structure and function. Here we investigate the principal sources of organic carbon supporting local shredder communities across a gradient in different levels of anthropogenic development along riverine reaches, in South Australia. In forested/wooded reaches with minimum to limited development, semi‐emergent macrophytes were the principal sources of organic carbon supporting the local shredder communities. However, in developed reaches, course particulate organic matter and filamentous algae were the principal food sources. The C:N ratios of the food sources in developed reaches were higher than those of their consumers indicating a stoichiometric mismatch. This imbalanced consumer‐resource nutrient ratio in those developed reaches is likely to impose constraints on the growth and reproduction of their aquatic shredder communities with probable knock‐on effects to higher trophic levels.
Linear declines in exotic and native plant species richness along an increasing altitudinal gradient in the Snowy Mountains, Australia
Authors: MALLEN‐COOPER JANE , PICKERING CATHERINE M.
Published: July 2008

Abstract  Declines in plant species richness with increasing altitude are common, but the form of the relationship can vary, with both monotonic decreasing relationships and humped relationship recorded. However, these different richness to altitude relationships may be due to methods that used different plot sizes/areas and survey efforts. To explore native and exotic plant richness along an altitudinal gradient in the Snowy Mountains of Australia, we consistently surveyed plots that were 120 m2 in area at 39 sites ranging from 540 to 2020 m. To relate exotic plant richness to disturbance, we surveyed plots at 16 sites along main roads and 23 sites along minor roads and also compared these 39 roadside plots to 120‐m2 plots located in undisturbed vegetation adjacent to the roadside (native plant richness was only surveyed in 25 of these 39 adjacent plots). We found a negative linear relationship between total, exotic and native species richness and altitude for plots on the side of main roads (16 sites) and minor roads (23 sites). For adjacent plots negative linear relationships were significant for all measures of species richness except for native species adjacent to major roads. As the pattern occurred for exotics it is less likely to be due to historical constraints on the species pools. The pattern could be influenced by difference in levels of disturbance along the gradient, although any such gradient in disturbance would have to apply to roadside and adjacent plots on major and minor roads. Therefore, it may be due to other factors such as changes in climate along the altitudinal gradient, although additional sampling including direct measures of climatic conditions, soil and disturbance factors would be needed to determine if this was the case.
Herbivores, but not other insects, are scarce on alien plants
Authors: PROCHEŞ ŞERBAN , WILSON JOHN R. U. , RICHARDSON DAVID M. , CHOWN STEVEN L.
Published: July 2008

Abstract  Understanding how the landscape‐scale replacement of indigenous plants with alien plants influences ecosystem structure and functioning is critical in a world characterized by increasing biotic homogenization. An important step in this process is to assess the impact on invertebrate communities. Here we analyse insect species richness and abundance in sweep collections from indigenous and alien (Australasian) woody plant species in South Africa's Western Cape. We use phylogenetically relevant comparisons and compare one indigenous with three Australasian alien trees within each of Fabaceae: Mimosoideae, Myrtaceae, and Proteaceae: Grevilleoideae. Although some of the alien species analysed had remarkably high abundances of herbivores, even when intentionally introduced biological control agents are discounted, overall, herbivorous insect assemblages from alien plants were slightly less abundant and less diverse compared with those from indigenous plants – in accordance with predictions from the enemy release hypothesis. However, there were no clear differences in other insect feeding guilds. We conclude that insect assemblages from alien plants are generally quite diverse, and significant differences between these and assemblages from indigenous plants are only evident for herbivorous insects.
Gene flow among native bush rat,Rattus fuscipes(Rodentia: Muridae), populations in the fragmented subtropical forests of south‐east Queensland
Authors: MACQUEEN P. E. , NICHOLLS J. A. , HAZLITT S. L. , GOLDIZEN A. W.
Published: July 2008

Abstract Many natural populations in areas of continuous habitat exhibit some form of local genetic structure. Anthropogenic habitat fragmentation can also strongly influence the dynamics of gene flow between populations. We used eight microsatellite markers to investigate the population genetic structure of an abundant forest species, the Australian bush rat (Rattus fuscipes), in the subtropical forests of south‐east Queensland. Five sites were sampled, allowing pairwise comparisons within continuous habitat and across clearings. Weak, but significant population differentiation and a significant pattern of isolation by distance was detected over the small scale (<10 km) of this study. Fine‐scale analysis at a single site (<1 km) showed a significant correlation between individual female genetic distance and geographical distance, but no similar pattern among male individuals. There was no evidence of increased population differentiation across clearings relative to comparisons within continuous forest. This was attributed to dispersal within corridors of remnant and revegetated habitat between the forested areas. We concluded that an inherently restricted dispersal ability, female philopatry and natural habitat heterogeneity play an important part in the development of genetic structure among populations ofR. fuscipes. It is important to understand the relationship between landscape features and the pattern of gene flow among continuous populations, as this allows us to predict the impact of fragmentation on natural populations.
Network plasticity in cortical assemblies
Authors: Chiappalone Michela , Massobrio Paolo , Martinoia Sergio
Published: July 2008

To investigate distributed synaptic plasticity at the cell assembly level, we used dissociated cortical networks from embryonic rats grown on grids of 60 extracellular substrate‐embedded electrodes (micro‐electrode arrays). We developed a set of experimental plasticity protocols based on the pairing of tetanic bursts (20 Hz) with low‐frequency stimuli (≤ 1 Hz), delivered through two separate channels of the array (i.e. associative tetanic stimulation). We tested our protocols on a large data set of 26 stable cultures, selected on the basis of both their initial level of spontaneous firing and the capability of low‐frequency test stimuli to evoke spikes. Our main results are summarized as follows: (i) low‐frequency stimuli produce neither short‐ nor long‐term changes in the evoked response of the network; (ii) associative tetanic stimulation is able to induce plasticity in terms of a significant increase or decrease of the evoked activity in the whole network; (iii) the amount of change (i.e. increase or decrease of the evoked firing) strongly depends on the specific features of the applied protocols; and (iv) the potentiation induced by a specific associative protocol can last several hours. The results obtained demonstrate that large in vitro cortical assemblies display long‐term network potentiation, a mechanism considered to be involved in the memory formation at cellular level. This pilot study could represent a relevant step towards understanding plastic properties at the neuronal population level.
Retinal transplants restore visual responses: trans‐synaptic tracing from visually responsive sites labels transplant neurons
Authors: Seiler Magdalene J. , Thomas Biju B. , Chen Zhenhai , Wu Rongjuan , Sadda Srinivas R. , Aramant Robert B.
Published: July 2008

This study aimed to test the hypothesis that visual responses in the superior colliculus (SC) originate from synaptic connections between fetal retinal transplants and degenerating host retinas. Sheets of embryonic day 19 rat retina expressing human placental alkaline phosphatase were transplanted to the subretinal space of 3‐ to 4‐week‐old S334ter‐line‐3 rats with fast retinal degeneration. Several months later, visual responses were recorded from the SC. Attenuated pseudorabies virus that is specifically transferred between neurons at synapses (strains PRV‐152, expressing green fluorescent protein (GFP) or BaBlu, expressing Escherichia coliβ‐galactosidase) was injected into the visually responsive site of the SC. After survival times of 1–2 days, the virus was detected in the retina by immunohistochemistry in combination with different retinal cell markers, such as protein kinase C, recoverin, calcium‐calmodulin‐dependent protein kinase II and glutamine synthetase. Transplanted rats had a mean response threshold of −3.1 log cd/m2 in a small area of the SC corresponding to the location of the graft in the retina. By 30 h after injection into this SC area, the virus traced back to host ganglion cells overlying the transplant and in close proximity to the transplant. By 2 days after injection, extensive virus label was found in the host retina and many cells in the transplant were also labeled. Virus‐labeled cells in the transplant were double labeled for neuronal and glial cell markers. This study provides anatomical evidence that synaptic connections between fetal retinal transplants and host retinas contribute to the visual responses in the SC.
Effects of corticosterone on corticotrophin‐releasing hormone and gastrin‐releasing peptide release in response to an aversive stimulus in two regions of the forebrain (central nucleus of the amygdala and prefrontal cortex)
Authors: Merali Zul , Anisman Hymie , James Jonathan S. , Kent Pam , Schulkin Jay
Published: July 2008

Previous research has shown that chronic corticosterone treatment increases the expression of corticotrophin‐releasing hormone (CRH) mRNA at the central nucleus of the amygdala (CeA). Like CRH, gastrin‐releasing peptide (GRP) appears to be involved in mediation of the stress response and is released at the CeA during exposure to an acute stressor. Using in‐vivo microdialysis, this study examined the effects of corticosterone treatment on the release of CRH and GRP in response to an airpuff challenge at two forebrain regions, the CeA and medial prefrontal cortex. Adrenally intact rats were treated with corticosterone by systemic implants over a 14‐day period prior to microdialysis probe insertion. We found that, at both regions, the airpuff‐induced CRH and GRP release were enhanced in the corticosterone pellet‐implanted rats as compared with the release observed in the vehicle‐implanted control rats. These findings suggest that chronic corticosterone exposure potentiates the stressor‐elicited release of CRH and GRP. As cortisol dysregulation has frequently been reported in people with psychiatric conditions, such as anxiety disorders or depression, a better understanding of the glucocorticoid‐mediating regulation of CRH and GRP may provide insight into the underlying neurochemical mechanisms involved in both adaptive fear‐type responses and maladaptive responses leading to pathology.
Regulation of ASIC activity by ASIC4 – new insights into ASIC channel function revealed by a yeast two‐hybrid assay
Authors: Donier Emmanuelle , Rugiero François , Jacob Céline , Wood John N.
Published: July 2008

ASIC4 is a member of the acid‐sensing ion channel family that is broadly expressed in the mammalian nervous system, but has no known function. We demonstrate here that transfected ASIC4 is targeted to the plasma membrane in CHO‐K1 cells, where it associates with ASIC1a and downregulates exogenous ASIC1a expression. This effect could also be observed on endogenous H+‐gated currents in TSA‐201 cells and ASIC3 currents in CHO‐K1 cells, suggesting a physiological role for ASIC4 in regulating ASIC currents involved in pain mechanisms. Using a yeast two‐hybrid assay we found that ASICs interact with proteins involved in diverse functions, including cytoskeletal proteins, enzymes, regulators of endocytosis and G‐protein‐coupled pathways. ASIC4 is the sole member of this ion channel class to interact strongly with polyubiquitin. The distinct functionally related sets of interacting proteins that bind individual ASICs identified in the yeast two‐hybrid screen suggest potential roles for ASICs in a variety of cellular functions.
Size variation and cell proliferation in chemosensory brain areas of a lizard (Podarcis hispanica): effects of sex and season
Authors: Sampedro Carlos , Font Enrique , Desfilis Ester
Published: July 2008

Many lizards rely on chemoreception for crucial aspects of their biology, including exploration, prey and predator detection, and intraspecific communication. Here we investigate sex and seasonal variation in size and proliferative activity in chemosensory areas of the lizard brain. We captured adult Iberian wall lizards (Podarcis hispanica) of either sex in the breeding (April) and non‐breeding (November) season, injected them with 5‐bromo‐2′‐deoxyuridine (BrdU) and killed them 3 weeks later. We removed the brains, measured the length of the olfactory bulbs, and counted BrdU‐labelled cells in the main and accessory olfactory bulbs (MOB, AOB), lateral cortex (LC) and nucleus sphericus (NS). Our results show that, relative to body size, males have larger MOBs and AOBs than females; however, relative to brain size, males have larger AOBs, but not larger MOBs than females. Additionally, males produce more new cells than females in the olfactory bulbs, LC and NS. We failed to detect significant seasonal changes or sex × season interaction in size or proliferative activity in these areas. Sex differences in the addition of newly generated cells – mainly neurons – may be partly responsible for the size differences in chemosensory brain areas. The presence of sexual dimorphism in AOB is expected given the available behavioural evidence, which suggests that males of P. hispanica are more responsive than females to socially relevant chemical stimuli. This is the first demonstration of sexual dimorphism in size and proliferative activity in chemosensory areas of a non‐mammalian species.
Multiple cerebellar zones are involved in the control of individual muscles: a retrograde transneuronal tracing study with rabies virus in the rat
Authors: Ruigrok Tom J. H. , Pijpers Angelique , Goedknegt‐Sabel Erika , Coulon Patrice
Published: July 2008

To identify cerebellar regions that are involved in the control of limb muscles, rabies virus was injected into the tibialis anterior (TA), the gastrocnemius (GC) or, for comparison, into the flexor digitorum (FD) muscles of the rat. Progression of retrograde transneuronal infection at supraspinal levels was assessed after variable time spans and was divided into three groups. Initially, infected neurons were observed in the reticular formation, lateral vestibular nucleus, red nucleus and motor cortex (group 1). Group 2 was characterized by labelling within the cerebellar nuclei as well as of two vermal strips of Purkinje cells (PCs). Double‐labelling with zebrin enabled identification of these strips as the lateral part of the A1‐ and B‐zone. For TA both zones were ipsilateral, whereas for GC the A1 strip predominated contralaterally. Group 3 infections showed additional labelling of multiple, in part bilateral, identifiable strips of PCs in vermis, paravermis and hemisphere. FD injections resulted in less robust labelling of vermal strips and more pronounced labelling within paravermal and hemispheral zonal regions. Only sporadic labelling in corresponding regions of the inferior olive and no labelling of cortical interneurons or granule cells was observed. Prolonged infection was seen to result in degeneration of PCs and possibly of motoneurons. We conclude that vermal, paravermal as well as hemispheral zones of the cerebellar cortex converge upon motoneurons that innervate a particular muscle. In addition, individual zones may control motorpools of different muscles and thus contribute to muscle synergies.
Spatial and temporal sensitivity degradation of primary visual cortical cells in senescent rhesus monkeys
Authors: Zhang Jie , Wang Xiusong , Wang Yongchang , Fu Yu , Liang Zhen , Ma Yuanye , Leventhal Audie G.
Published: July 2008

Human visual function declines with age. Much of this decline is mediated by changes in the central visual pathways. In this study we compared the spatial and temporal sensitivities of striate cortical cells in young and old paralysed macaque monkeys. Extracellular single‐unit recordings were employed. Our results show that cortical neurons in old monkeys exhibit lower optimal spatial and temporal frequencies, lower spatial resolution and lower high temporal frequency cut‐offs than do cells in young adult monkeys. These changes in old monkeys are accompanied by increased visually evoked responses, increased spontaneous activities and decreased signal‐to‐noise ratios. The increased excitability of cells in old animals is consistent with an age‐related degeneration of intracortical inhibition. The degradation of spatial and temporal function in old striate cortex should contribute to the decline in visual function that accompanies normal aging.
Sex differences in cell proliferation and glucocorticoid responsiveness in the zebra finch brain
Authors: Katz Amnon , Mirzatoni Anahid , Zhen Yin , Schlinger Barney A.
Published: July 2008

Neural proliferation is a conserved property of the adult vertebrate brain. In mammals, stress reduces hippocampal neuronal proliferation and the effect is stronger in males than in females. We tested the effects of glucocorticoids on ventricular zone cell proliferation in adult zebra finches where neurons are produced that migrate to and incorporate within the neural circuits controlling song learning and performance. Adult male zebra finches sing and have an enlarged song circuitry; females do not sing and the song circuit is poorly developed. Freshly prepared slices from adult males and females containing the lateral ventricles were incubated with the mitotic marker BrdU with or without steroid treatments. BrdU‐labeled cells were revealed immunocytochemically and all labeled cells within the ventricular zone were counted. We identified significantly higher rates of proliferation along the ventricular zone of males than in females. Moreover, acute administration of corticosterone significantly reduced proliferation in males with no effects in females. This effect in males was replicated by RU‐486, which appears to act as an agonist of the glucocorticoid receptor in the songbird brain. The corticosterone effect was reversed by Thiram, which disrupts corticosterone action on the glucocorticoid receptor. Sex differences in proliferation and responses to stress hormones may contribute to the sexually dimorphic and seasonal growth of the neural song system of songbirds.
Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia
Authors: Wang Yanping , Luo Jing , Chen Xinzhi , Chen Hai , Cramer Sam W. , Sun Dandan
Published: July 2008

We investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)‐mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min of middle cerebral artery occlusion were similar in wild‐type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/−) mice. NHE1+/+ mice developed infarct volume of 57.3 ± 8.8 mm3 at 24 h reperfusion (Rp), which progressed to 86.1 ± 10.0 mm3 at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis‐inducing factor (AIF), activation of caspase‐3, and TUNEL‐positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/− mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase‐3 was significantly reduced in NHE1+/− brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up‐regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis.
Behavioural profile of a new mouse model for NPY deficiency
Authors: Karl Tim , Duffy Liesl , Herzog Herbert
Published: July 2008

The abundantly expressed neuropeptide Y (NPY) plays an important role in anxiety and stress reactivity, as exogenous NPY administration reduces anxiety‐like behaviour in rodents. However, unlike the potent effects of NPY seen in pharmacological studies, two independent examinations of a genetic mouse model for NPY deficiency have shown only subtle, inconsistent and task‐dependent anxiety‐related phenotypes for male mutants. Here we present results of a newly developed germline NPY‐knockout model, which has been characterized behaviourally using a comprehensive multi‐tiered phenotyping strategy. Mice of both sexes were investigated in locomotion and exploration tasks, anxiety‐related paradigms, a hippocampus‐dependent memory test and a battery of basic tasks screening for sensory and motor functions. Male and female NPY‐deficient mice consistently demonstrated suppressed levels of locomotion and exploration. Furthermore, mutant mice exhibited a pronounced anxiogenic‐like phenotype when tested in spatiotemporal anxiety‐relevant paradigms (i.e. elevated‐plus maze, open field and light–dark task). Importantly, this phenotype was more pronounced in male NPY mutants, revealing a moderate sexually dimorphic impact of NPY deficiency on behaviour. Interestingly, lack of NPY did not result in impaired learning and memory in either sex. Our carefully selected comprehensive behavioural phenotyping strategy revealed a consistent hypolocomotive and sex‐dependent anxious‐like phenotype. This new NPY‐knockout mouse model reveals the importance of sex‐specific testing. It also offers a potent new model for research into anxiety‐related disorders and suggests potential treatment options for these conditions via the NPY system.
GDNF hyperalgesia is mediated by PLCγ, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4‐binding protein versican
Authors: Bogen Oliver , Joseph Elizabeth K. , Chen Xiaojie , Levine Jon D.
Published: July 2008

The function of the isolectin B4 (IB4+)‐binding and GDNF‐dependent Ret (Ret+)‐expressing non‐peptidergic subpopulation of nociceptors remain poorly understood. We demonstrate that acute administration of GDNF sensitizes nociceptors and produces mechanical hyperalgesia in the rat. Intrathecal IB4–saporin, a selective toxin for IB4+/Ret+‐nociceptors, attenuates GDNF but not NGF hyperalgesia. Conversely, intrathecal antisense to Trk A attenuated NGF but not GDNF hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides targeting mRNA for versican, the molecule that renders the Ret‐expressing nociceptors IB4‐positive (+), also attenuated GDNF but not NGF hyperalgesia, as did ADAMTS‐4, a matrix metalloprotease known to degrade versican. Finally, inhibitors for all five signaling pathways known to be activated by GDNF at GFRα1/Ret: PLCγ, CDK5, PI3K, MAPK/ERK and Src family kinases, attenuated GDNF hyperalgesia. Our results demonstrate a role of the non‐peptidergic nociceptors in pain produced by the neurotrophin GDNF and suggest that the IB4‐binding protein versican functions in the expression of this phenotype.
The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory‐related activity of hypoglossal motoneurons in the adult rat
Authors: Montero Fernando , Portillo Federico , González‐Forero David , Moreno‐López Bernardo
Published: July 2008

Motoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory‐related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton‐like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro‐iontophoretically applied while performing single‐unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory‐related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell‐permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co‐addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory‐related activity of HMNs by a cGMP‐dependent mechanism in physiological conditions.
EGb761 protects against nigrostriatal dopaminergic neurotoxicity in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinsonism in mice: role of oxidative stress
Authors: Rojas Patricia , Serrano‐García Norma , Mares‐Sámano José J. , Medina‐Campos Omar Noel , Pedraza‐Chaverri José , Ögren Sven Ove
Published: July 2008

1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents. Previous studies suggest that oxidative stress, via free radical production, is involved in MPTP‐induced neurotoxicity. The MPTP‐treated mouse has been the most widely used model for assessing neuroprotective agents for Parkinson’s disease. It has been reported previously that EGb761 prevents dopaminergic neurotoxicity of MPTP. This compound is multifunctional via different mechanisms. Here, we report the neuroprotective effect of EGb761 against oxidative stress induced by MPTP in C57BL/6J mice. EGb761 is a patented and well‐defined mixture of active compounds extracted from Ginkgo biloba leaves, with neuroprotective effects, exerted probably via its antioxidant or free radical scavenger action. MPTP administration resulted in a significant decrease in striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. Mice receiving EGb761 had significantly attenuated MPTP‐induced loss of striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. The neuroprotective effect of EGb761 against MPTP neurotoxicity is associated with blockade of lipid peroxidation and reduction of superoxide radical production (indicated by a down‐regulation of Mn‐superoxide dismutase activity), both of which are indices of oxidative stress. Behavioral analyses showed that EGb761 improved MPTP‐induced impairment of locomotion in a manner that correlated with enhancement of striatal dopamine levels. These findings suggest that, in mice, EGb761 attenuates MPTP‐induced neurodegeneration of the nigrostriatal pathway and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.
Multiple functions of GABAA and GABAB receptors during pattern processing in the zebrafish olfactory bulb
Authors: Tabor Rico , Yaksi Emre , Friedrich Rainer W.
Published: July 2008

γ‐Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in the processing of activity patterns in the olfactory bulb (OB), but their functions have been difficult to study during odor responses in the intact system. We pharmacologically manipulated GABAA and GABAB receptors in the OB of zebrafish and analysed the effects on odor responses of the output neurons, the mitral cells (MCs), by electrophysiological recordings and temporally deconvolved two‐photon Ca2+ imaging. The blockade of GABAB receptors enhanced presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude and time course of a subset of MC responses, indicating that GABAB receptors have a modulatory influence on OB output activity. The blockade of GABAA receptors induced epileptiform firing, enhanced excitatory responses and abolished fast oscillations in the local field potential. Moreover, the topological reorganization and decorrelation of MC activity patterns during the initial phase of the response was perturbed. These results indicate that GABAA receptor‐containing circuits participate in the balance of excitation and inhibition, the regulation of total OB output activity, the synchronization of odor‐dependent neuronal ensembles, and the reorganization of odor‐encoding activity patterns. GABAA and GABAB receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB.
Pathway‐dependent modulation by P2‐purinoceptors in the mouse retina
Authors: Kaneda Makoto , Ishii Toshiyuki , Hosoya Toshihiko
Published: July 2008

Adenosine trisphosphate (ATP) activates purinoceptors and acts as a neurotransmitter in the nervous system. In the retina, we previously reported that the immunohistochemical distribution of the subset of P2‐purinoceptors differs between the ON and OFF pathways. Here, we investigated whether ATP activates P2‐purinoceptors and modulates the physiological function of the mouse retina. We also examined if signal processing by P2‐purinoceptors is pathway specific. Results showed that ATP activated both ON‐ and OFF‐cholinergic amacrine cells. However, responses in OFF‐cholinergic amacrine cells were greater than those in ON‐cholinergic amacrine cells. Pharmacological studies in OFF‐cholinergic amacrine cells showed that the response of OFF‐cholinergic amacrine cells is mediated P2X2‐purinoceptors. Further, ATP increased γ‐aminobutyric acid (GABA)ergic inhibitory postsynaptic currents (IPSCs) in OFF‐ but not ON‐cholinergic amacrine cells. The increase in GABAergic IPSCs was mediated by P2‐purinoceptors. P2‐purinoceptor‐mediated signals suppressed OFF ganglion cells but activated ON ganglion cells. Our findings indicate that ATP physiologically modulates signal processing of the ON and OFF pathways in a pathway‐specific manner through P2‐purinoceptors.
Divergent phosphorylation pattern of tau in P301L tau transgenic mice
Authors: Deters Natasha , Ittner Lars M. , Götz Jürgen
Published: July 2008

Aggregates of hyperphosphorylated tau are prominent in brains of patients with Alzheimer’s disease or frontotemporal dementia (FTD). They have been reproduced in animal models following the identification of tau mutations in familial cases of FTD. This includes our previously generated transgenic model, pR5, which expresses FTD (P301L) mutant tau in neurons. The mice are characterized by tau aggregation including tangle (NFT) formation, memory impairment and mitochondrial dysfunction. In 8‐month‐old mice, S422 phosphorylation of tau is linked to NFT formation, however, a detailed analysis of tau solubility, phosphorylation and aggregation has not been done nor have the mice been monitored until a high age. Here, we undertook an analysis by immunohistochemistry, Gallyas impregnation and Western blotting of brains from 3 month‐ up to 20 month‐old mice. NFTs first appeared at 6 months in the amygdala, followed by the CA1 region of the hippocampus. As the mice get older, the solubility of tau is decreased as determined by sequential extractions. Histological analysis revealed increased phosphorylation at the AT180, AT270 and 12E8 epitopes with ageing. The numbers of AT8‐positive neurons increased from 3 to 6 months old. However, whereas S422 appeared only late and concomitantly with NFT formation, the only neurons left with AT8‐reactivity at 20 months were those that had undergone NFT formation. As hyperphosphorylated tau continued to accumulate, the lack of AT8‐reactivity suggests regulatory mechanisms in specifically dephosphorylating the AT8 epitope in the remaining neurons. Thus, differential regulation of phosphorylation is important for NFT formation in neurodegenerative diseases with tau pathology.
Types and synaptic connections of hippocampal inhibitory neurons reciprocally connected with the medial septum
Authors: Takács Virág T. , Freund Tamás F. , Gulyás Attila I.
Published: July 2008

The morphological properties and connectivity of γ‐aminobutyric acid (GABA)ergic hippocampal cells projecting to the medial septum (HS cells) were examined in the rat. Two types of HS cells are located in different layers of the hippocampus: sparsely‐spiny cells are in CA1–3 str. oriens and CA3 str. radiatum, where recurrent axons of pyramidal cells arborize. Densely‐spiny HS cells with spiny somata are located in the termination zone of granule cell axons. In the hilus, intermediate morphologies can also be found. HS cells receive GABAergic medial septal afferents in all layers where they occur, thus the connectivity of the septum and the hippocampus is reciprocal at cell level. HS cells receive extremely dense innervation, sparsely‐spiny cells are innervated by ∼19 000 excitatory inputs, while densely‐spiny cells get an even larger number (∼37 000). While 14% of the inputs are inhibitory for the sparsely‐spiny cells, it is only 2.3% in the case of densely‐spiny cells. Because a high proportion (up to 54.5% on somata and 27.5% on dendrites) of their GABAergic inputs derived from labelled septal terminals, their predominant inhibitory input probably arises from the medial septum. CA1 area HS cells possessed myelinated projecting axons, as well as local collaterals, which targeted mostly pyramidal cell dendrites and spines in str. oriens and radiatum. The synaptic organization suggests that by sampling the activity of large populations of principal cells HS cells can reliably broadcast hippocampal activity level to the medial septum.
Ephrin‐A5 acts as a repulsive cue for migrating cortical interneurons
Authors: Zimmer Geraldine , Garcez Patricia , Rudolph Judith , Niehage Ronny , Weth Franco , Lent Roberto , Bolz Jürgen
Published: July 2008

Cortical interneurons are born in the germinative zones of the ganglionic eminences in the subpallium, and migrate tangentially in spatially and temporally well‐defined corridors into the neocortex. Because ephrin‐A5 is expressed in the ventricular zone (VZ) of the ganglionic eminences at these developmental stages, we examined the possible effects of this molecule on interneuron migration. Double‐immunocytochemistry of dissociated neurons from the medial ganglionic eminences (MGE) revealed that calbindin‐positive cells express the EphA4‐receptor. In situ, EphA4 is strongly expressed in the subventricular zone of the ganglionic eminences. Using different in vitro assays, we found that ephrin‐A5 acts as a repellent cue for MGE neurons. We then examined interneuron migration in slice overlay experiments, where MGE‐derived explants from enhanced green fluorescent protein‐expressing transgenic mice were homotopically grafted into host slices from wild‐type littermate embryos. In these in vitro preparations, interneurons recapitulated in vivo cell migration in several respects. However, interneurons in brain slices also migrated in the VZ of the ganglionic eminences, a region that is strictly avoided in vivo. In situ hybridizations revealed that ephrin‐A5 became downregulated in the VZ in vitro. When recombinant ephrin‐A5‐Fc was added to the slices, it preferentially bound to the VZ, and migrating MGE neurons avoided the VZ as in vivo. The restoration of the normal migration pathway in slices required ephrin‐A5 clustering and signalling of Src family kinases. Together, these experiments suggest that ephrin‐A5 acts as an inhibitory flank that contributes to define the pathway of migrating interneurons.
Non‐stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll‐like receptor 4 (TLR4)
Authors: Hutchinson Mark R. , Zhang Yingning , Brown Kimberley , Coats Benjamen D. , Shridhar Mitesh , Sholar Paige W. , Patel Sonica J. , Crysdale Nicole Y. , Harrison Jacqueline A. , Maier Steven F. , Rice Kenner C. , Watkins Linda R.
Published: July 2008

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll‐like receptor 4 (TLR4) may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury (CCI). Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived from lipopolysaccharide. Additionally, (+)‐naltrexone, (+)‐naloxone, and (−)‐naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293‐TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI‐induced microglial activation by (+)‐naloxone and (−)‐naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron‐to‐glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists (+)‐naloxone and (−)‐naloxone can each fully reverse established neuropathic pain upon multi‐day administration. This finding with (+)‐naloxone is of potential clinical relevance. This is because (+)‐naloxone is an antagonist that is inactive at the (−)‐opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that (+)‐opioid antagonists such as (+)‐naloxone may be useful clinically to suppress glial activation, yet (−)‐opioid agonists suppress pain.
Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina
Authors: VanGuilder Heather D. , Brucklacher Robert M. , Patel Kruti , Ellis Rhona W. , Freeman Willard M. , Barber Alistair J.
Published: July 2008

Diabetic retinopathy can result in vision loss and involves progressive neurovascular degeneration of the retina. This study tested the hypothesis that diabetes decreases the retinal expression of presynaptic proteins involved in synaptic function. The protein and mRNA contents for synapsin I, synaptophysin, vesicle‐associated membrane protein 2, synaptosomal‐associated protein of 25 kDa and postsynaptic density protein of 95 kDa were measured by immunohistochemistry, immunoblotting and real‐time quantitative polymerase chain reaction in whole retinas and retinal synaptosomes from streptozotocin‐diabetic and control Sprague–Dawley rats. There was less presynaptic protein immunoreactivity after 1 and 3 months of diabetes than in controls. Discrete synaptophysin‐immunoreactive puncta were significantly smaller and fewer in sections from 1‐ and 3‐month diabetic rat retinas than in those from controls. The content of presynaptic proteins was significantly less in whole retinas of 1‐ and 3‐month diabetic rats, and in synaptosomes from 1‐month diabetic rats, than in controls. Whole retinas had significantly less mRNA for these genes after 3 months but not 1 month of diabetes, as compared to controls (with the exception of postsynaptic density protein of 95 kDa). In contrast, there was significantly less mRNA for synaptic proteins in synaptosomes of 1‐month diabetic rats than in controls, suggesting a localized depletion at synapses. Protein and mRNA for β‐actin and neuron‐specific enolase were unchanged by diabetes. The ratio of phosphorylated to total synapsin I was also reduced in whole retina and isolated synaptosomes from 1‐month diabetic rats, as compared to controls. These data suggest that diabetes has a profound impact on presynaptic protein expression in the retina, and may provide a mechanism for the well‐established defects in vision and the electrophysiological response of the retina in diabetes.
Omi / HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntington’s disease
Authors: Inagaki Reina , Tagawa Kazuhiko , Qi Mei‐Ling , Enokido Yasushi , Ito Hikaru , Tamura Takuya , Shimizu Shigeomi , Oyanagi Kityomitsu , Arai Nobutaka , Kanazawa Ichiro , Wanker Erich E , Okazawa Hitoshi
Published: July 2008

Selective vulnerability of neurons is a critical feature of neurodegenerative diseases, but the underlying molecular mechanisms remain largely unknown. We here report that Omi/HtrA2, a mitochondrial protein regulating survival and apoptosis of cells, decreases selectively in striatal neurons that are most vulnerable to the Huntington’s disease (HD) pathology. In microarray analysis, Omi/HtrA2 was decreased under the expression of mutant huntingtin (htt) in striatal neurons but not in cortical or cerebellar neurons. Mutant ataxin‐1 (Atx‐1) did not affect Omi/HtrA2 in any type of neuron. Western blot analysis of primary neurons expressing mutant htt also confirmed the selective reduction of the Omi/HtrA2 protein. Immunohistochemistry with a mutant htt‐transgenic mouse line and human HD brains confirmed reduction of Omi/HtrA2 in striatal neurons. Overexpression of Omi/HtrA2 by adenovirus vector reverted mutant htt‐induced cell death in primary neurons. These results collectively suggest that the homeostatic but not proapoptotic function of Omi/HtrA2 is linked to selective vulnerability of striatal neurons in HD pathology.
Emergency laparoscopic surgery for complicated diverticular disease
Authors: Titu L. V. , Zafar N. , Phillips S. M. , Greenslade G. L. , Dixon A. R.
Published: July 2008

Objective  The aim of this study was to analyse the outcome of emergency laparoscopic surgical management of complicated diverticular disease.

Method  A prospectively collected electronic database of all colorectal laparoscopic procedures between April 2001 and September 2007 has been used to identify outcomes in patients presenting with complicated diverticular disease.

Results  Sixty‐six patients (28 men), median age 69 years (23–95), ASA grade II (12), III (38), IV (16) have undergone emergency surgery for complicated diverticulitis – Hinchey grades I (27), II (29), III (7) and diverticular bleeding (3) over a 6½‐year period: 43 high anterior resections, 17 Hartmann’s resections and seven low anterior resections. Diverticular fistulas were seen in 16 patients: colovaginal (7), colovesical (2), colo‐fallopian (4), entero‐colic (3). The median operation time was 110 min (45–195 min). There was one conversion to open surgery. Postoperative analgesia was provided by intravenous Paracetamol in 33 patients (50%), patient‐controlled analgesia in 24 (36%), oral Paracetamol and Oramorph (12%) and epidural opioid infusion (1.5%). The median time to normal diet was 24 h (4 h–6 days) and median hospital stay 5 days (2–30). There were two deaths (3.3%); anastomotic leak, ventricular fibrillation (VF) cardiac arrest. Other complications included: wound infection eight (12%), anastomotic leak four (8%), port‐site hernia one and one case of Clostridium difficile colitis requiring colectomy. There were five (7.5%) returns to theatre and two readmissions (3%).

Conclusion  Laparoscopic resectional surgery in complicated diverticular disease is a feasible, safe and a largely predictable operation that allows for early hospital discharge and, in our opinion, improved patient care. We are encouraged to continue to offer our patients the option of an emergency laparoscopic resection.
Rectal cancer in young adults: a series of 102 patients at a tertiary care centre in India
Authors: Nath J. , Wigley C. , Keighley M. R. B. , Perakath B.
Published: July 2008

Objective  Rectal cancer in young patients is uncommon. There is little information on rectal cancer in young adults in India. The aim of this study was to determine the relative incidence of rectal cancer in young patients in India and identify any differences in histological grade and pathological stage between younger and older cohorts.

Method  All adult patients presenting at a tertiary colorectal unit with primary rectal adenocarcinoma between September 2003 and August 2007 were included. Patients were divided into two groups: 40 years and younger, and older than 40 years. Details regarding patient demographics, preoperative assessment, management and tumour grade and stage were obtained from a prospectively maintained database.

Results  One hundred and two of 287 patients (35.5%) were 40 or younger at presentation. Younger patients were more likely to present with less favourable histological features (52.0%vs 20.5% (P < 0.001)) and low rectal tumours (63.0%vs 50.0%) (P = 0.043), but were equally likely to undergo curative surgery compared to the older group (P = 0.629). Younger patients undergoing surgery had a higher pathological T stage (T0–2 18.9%, T3 62.3%, T4 19.7%vs 34.5%, 56.0%, 9.5%) (P = 0.027) and more advanced pathological N stage (N0 31.1%, N1 41.0%, N2 27.9%vs 53.4%, 26.7%, 17.2%) (P = 0.014).

Conclusion  The relative number of young patients with rectal cancer in this Indian series is higher than figures reported in western populations. The reasons for this are not clear. The histopathological features of rectal tumours in young patients in this study are consistent with similar studies in Western populations.
A review of adherence to drug therapy in patients with overactive bladder
Authors: Basra Ramandeep K. , Wagg Adrian , Chapple Christopher , Cardozo Linda , Castro‐Diaz David , Pons Montserrat Espuna , Kirby Mike , Milsom Ian , Vierhout Mark , Van Kerrebroeck Philip , Kelleher Con
Published: July 2008

Drug therapy for overactive bladder (OAB) is associated with improvements in symptoms and quality of life, but the short‐ and long‐term adherence and persistence is suboptimal. In this review we outline methods of measuring, and factors affecting, adherence to pharmacotherapy in patients with OAB. Clinical practice suggests that adherence rates reported in clinical trials are much greater than in real practice. Factors affecting adherence include psychological and social variables that might alter patients’ perception of the benefits of taking medication, and the effect of comorbidity and polypharmacy. Whilst there is some evidence that lack of efficacy and side‐effects are contributory, these additional factors are also important.