bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial oxidative metabolism in motor neuron degeneration (mnd) mouse central nervous system
Authors: Bertamini M. , Marzani B. , Guarneri R. , Guarneri P. , Bigini P. , Mennini T. , Curti D. 
Published: March 2003

AbstractThe mnd mouse spontaneously develops slowly evolving motoneuron pathology leading to progressive motor impairment. There is strong evidence that a complex interplay between oxidative stress, mitochondria abnormalities and alteration of glutamate neurotransmission plays an important role in the pathogenesis of motor neuron diseases. Therefore, we investigated the presence of mitochondrial dysfunction in frontal, central (comprising the motor area) and occipital regions of the cerebral cortex and in the spinal cord of 35‐week‐old mnd mice. Lipid peroxide derivatives reacting with thiobarbituric acid (TBARS) were measured in the cervical, thoracic and lumbar spinal cord. In addition biochemical and behavioural analyses were carried out in mnd mice chronically treated with l‐carnitine from the 11th to the 34th week of life (mndT mice). Slight but significant alterations of mitochondrial enzyme activities were seen in the mnd cortical regions. The central area was the most affected and both complex I, IV and citrate synthase were decreased with respect to controls. The rate of oxygen consumption (QO2) was markedly decreased in both the upper (cervical + upper portion of the thoracic region) and lower (lumbar + lower portion of the thoracic region) mnd spinal cord. The level of TBARS showed a rostro‐caudal trend to increase, being 30% higher in the lumbar tract of mnd mice in comparison with controls. l‐carnitine treatment increased the mitochondrial enzyme activities in cortical regions towards control value and was effective in enhancing QO2 and decreasing TBARS levels in the spinal cord of mndT. Behavioural testing showed that l‐carnitine significantly delayed the onset of motor behaviour impairment. This beneficial effect was declining at 35 week of age, when the biochemical measurements were performed.
Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat
Authors: Willing Alison E. , Zigova Tanja , Milliken Melissa , Poulos Steve , Saporta Samuel , McGrogan Michael , Snable Gary , Sanberg Paul R. 
Published: March 2003

AbstractLithium (Li +) treatment of NTera2/D1 (or hNT Neurons) in culture increases tyrosine hydroxylase (TH) expression in this cell‐line [Zigova et al., (1999) Exp. Neurol., 157, 251–258]. It is not known if these Li + treated cells maintain TH expression once transplanted into the striatum of the hemiparkinsonian rats. hNT neurons were either treated with 1 mm LiCl or left untreated and then transplanted into the striatum of Sprague‐Dawley rats. Some cells were exposed to the lithium for 24 h in culture while others were exposed only briefly (2–3 h) just prior to transplantation. We also examined whether Li + treatment of the animal after transplantation (0.24% w/w lithium carbonate in chow) was effective in increasing neuronal survival. One week after transplantation, the animals were perfused with 4% paraformaldehyde and immunocytochemistry was performed on 30 µm sections through the transplant. Human nuclear matrix antigen immunostaining demonstrated that there was significantly better survival of cells in the group treated briefly with lithium compared to all other groups. Brief exposure to lithium resulted in a greater expression of TH in situ as well. Neuron specific enolase immunohistochemistry showed that there was extensive fibre outgrowth in all groups. These results suggest that brief Li + exposure may enhance survival to over 60% and increase TH expression of hNT Neurons transplanted in the hemiparkinsonian rat nearly three‐fold.
Aggresome‐related biogenesis of Lewy bodies
Authors: McNaught Kevin St P. , Shashidharan P. , Perl Daniel P. , Jenner Peter , Olanow C. Warren 
Published: March 2003

AbstractNeurodegenerative disorders such as Parkinson's disease (PD) and ‘dementia with Lewy bodies’ (DLB) are characterized pathologically by selective neuronal death and the appearance of intracytoplasmic protein aggregates (Lewy bodies). The process by which these inclusions are formed and their role in the neurodegenerative process remain elusive. In this study, we demonstrate a close relationship between Lewy bodies and aggresomes, which are cytoplasmic inclusions formed at the centrosome as a cytoprotective response to sequester and degrade excess levels of potentially toxic abnormal proteins within cells. We show that the centrosome/aggresome‐related proteins γ‐tubulin and pericentrin display an aggresome‐like distribution in Lewy bodies in PD and DLB. Lewy bodies also sequester the ubiquitin‐activating enzyme (E1), the proteasome activators PA700 and PA28, and HSP70, all of which are recruited to aggresomes for enhanced proteolysis. Using novel antibodies that are specific and highly sensitive to ubiquitin–protein conjugates, we revealed the presence of numerous discrete ubiquitinated protein aggregates in neuronal soma and processes in PD and DLB. These aggregates appear to be being transported from peripheral sites to the centrosome where they are sequestered to form Lewy bodies in neurons. Finally, we have shown that inhibition of proteasomal function or generation of misfolded proteins cause the formation of aggresome/Lewy body‐like inclusions and cytotoxicity in dopaminergic neurons in culture. These observations suggest that Lewy body formation may be an aggresome‐related event in response to increasing levels of abnormal proteins in neurons. This phenomenon is consistent with growing evidence that altered protein handling underlies the etiopathogenesis of PD and related disorders.
The effect of bilateral deafness on excitatory and inhibitory synaptic strength in the inferior colliculus
Authors: Vale Carmen , Sanes Dan H. 
Published: March 2003

AbstractThe consequences of deafness on the central auditory nervous system have been examined at many levels, from molecular to functional. However, there has never been a direct and selective measurement of excitatory synaptic function following total hearing loss. In the present study, gerbils were deafened at postnatal day 9, an age at which there is no deafferentation‐induced cell death of ventral cochlear nucleus neurons. One to five days after bilateral cochlear ablation, the amplitude of evoked excitatory postsynaptic currents (EPSC) was measured with whole‐cell voltage‐clamp recordings in an inferior colliculus (IC) brain slice preparation in response to electrical stimulation of the ipsilateral lateral lemniscus (LL) or the commissure of the inferior colliculus (CIC). Deafness resulted in larger LL‐ and CIC‐evoked EPSC amplitudes and durations. This result was observed at a depolarized holding potential. In addition, deafness caused a decrease in excitatory neurotransmitter release at the LL pathway, as assessed with a paired‐pulse stimulation protocol. In contrast to its effect on excitatory synapses, bilateral cochlear ablation reduced inhibitory synaptic strength in IC neurons. The effects included a postsynaptic decrease in IPSC conductance, a 25‐mV depolarization in the IPSC equilibrium potential and a decrease of neurotransmitter release. Thus normal innervation differentially affects excitatory and inhibitory synaptic strength in IC neurons, and these changes may contribute to alterations in auditory coding properties following sensory deprivation.
Selective ablation of olfactory receptor neurons without functional impairment of vomeronasal receptor neurons in OMP‐ntr transgenic mice
Authors: Ma Dan , Allen Nicholas D. , Van Bergen Yfke C. H. , Jones Camilla M. E. , Baum Michael J. , Keverne E. Barry , Brennan Peter A. 
Published: March 2003

AbstractThis study used transgenic mice, in which expression of a bacterial nitroreductase (ntr) gene was linked to the expression of olfactory marker protein (OMP). The nitroreductase enzyme is thus expressed in mature chemosensory neurons of these OMP‐ntr transgenic mice, and converts the pro‐drug CB1954 to a cytotoxic form, specifically killing these neurons. Systemic injections of the pro‐drug led to the ablation of receptor neurons in both the main olfactory and vomeronasal epithelia. Due to the anatomical separation of the epithelia, however, when the pro‐drug was administered by intranasal infusion only the receptors of the main olfactory epithelium were destroyed. This procedure resulted in a profound deficit in olfactory investigation and discrimination in a habituation–dishabituation test, whereas the pregnancy blocking effect of male pheromones, which is mediated via the vomeronasal system was unaffected. OMP‐ntr mice receiving intranasal infusion of pro‐drug had not recovered any significant main olfactory function at 24 days following treatment. This novel technique could potentially be applied to selectively ablate olfactory receptor neurons expressing a particular olfactory receptor by linking its expression to that of the nitroreductase enzyme.
The murine neurokinin NK1 receptor gene contributes to the adult hypoxic facilitation of ventilation
Authors: Ptak Krzysztof , Burnet Henri , Blanchi Bruno , Sieweke Michael , De Felipe Carmen , Hunt Stephen P. , Monteau Roger , Hilaire Gérard 
Published: March 2003

AbstractSubstance P and neurokinin‐1 receptors (NK1) modulate the respiratory activity and are expressed early during development. We tested the hypothesis that NK1 receptors are involved in prenatal development of the respiratory network by comparing the resting respiratory activity and the respiratory response to hypoxia of control mice and mutant mice lacking the NK1 receptor (NK1−/−). In vitro and in vivo experiments were conducted on neonatal, young and adult mice from wild‐type and NK1−/− strains. In the wild strain, immunohistological, pharmacological and electrophysiological studies showed that NK1 receptors were expressed within medullary respiratory areas prior to birth and that their activation at birth modulated central respiratory activity and the membrane properties of phrenic motoneurons. Both the membrane properties of phrenic motoneurons and the respiratory activity generated in vitro by brainstem‐spinal cord preparation from NK1−/− neonate mice were similar to that from the wild strain. In addition, in vivo ventilation recordings by plethysmography did not reveal interstrain differences in resting breathing parameters. The facilitation of ventilation by short‐lasting hypoxia was similar in wild and NK1−/− neonates but was significantly weaker in adult NK1−/− mice. Results demonstrate that NK1 receptors do appear to be necessary for a normal respiratory response to short‐lasting hypoxia in the adult. However, NK1 receptors are not obligatory for the prenatal development of the respiratory network, for the production of the rhythm, or for the regulation of breathing by short‐lasting hypoxia in neonates.
Extracellular acid increases the open probability of transduction channels in spider mechanoreceptors
Authors: Höger Ulli , French Andrew S. 
Published: March 2003

AbstractIon channels of the epithelial sodium channel, degenerin and acid‐sensitive channel (ENaC/DEG/ASIC) family share a number of structural and functional homologies. Several members of this group have been linked to mechanoreception and nociception, but there is no direct evidence that these molecules cause the transduction of mechanical stimuli in any mechanoreceptor. The receptor channels of a spider mechanoreceptor, the VS‐3 slit‐sense organ of Cupiennius salei, show several similarities to ENaC/DEG/ASIC channels, including Na+ selectivity and amiloride blockade. We recorded the receptor current under voltage clamp in VS‐3 neurons at different extracellular pH values. Acid pH partially blocked the delayed rectifier K+ current and increased the receptor current in these cells. Noise analysis of the receptor current showed that low pH increased the open probability of the receptor channels. Therefore, acid sensitivity is a further similarity between these mechanoreceptor channels and the ENaC/DEG/ASIC family.
Saturation and self‐inhibition of rat hippocampal GABAA receptors at high GABA concentrations
Authors: Mercik Katarzyna , Zarnowska Ewa D. , Mandat Maria , Mozrzymas Jerzy W. 
Published: March 2003

AbstractCurrent responses to ultrafast γ‐aminobutyric acid (GABA) applications were recorded from excised patches in rat hippocampal neurons to study the gating properties of GABAA receptors at GABA concentrations close to saturating ones and higher. The amplitude of currents saturated at approximately 1 mm, while the onset rate of responses reached saturation at 4–6 mm GABA. At high GABA concentrations (> 10 mm), the amplitude of current responses was reduced in a dose‐dependent manner with a half‐blocking GABA concentration of approximately 50 mm. The peak reduction at high GABA doses was accompanied by a tendency to increase the steady‐state to peak ratio. At concentrations higher than 30 mm, this effect took the form of a rebound current, i.e. during the prolonged GABA applications, the current firstly declined due to desensitization onset and then, instead of decreasing towards a steady‐state value, clearly increased. Both the self‐inhibition of GABAA receptors by high GABA doses and rebound were clearly voltage dependent, being larger at positive holding potentials. The fast desensitization component accelerated with depolarization at all saturating [GABA] tested. The rebound phenomenon indicates that the self‐block of GABAA receptors is state dependent, and suggests that the sojourn in the desensitized conformation provides a ‘rescue’ from the block. We propose that high GABA concentrations inhibit the receptors by direct occlusion of the channel pore having no effect on the receptor gating.
Compartment‐specific changes in striatal neuronal activity during expression of amphetamine sensitization are the result of drug hypersensitivity
Authors: Vanderschuren Louk J. M. J. , Schoffelmeer Anton N. M. , Van Leeuwen Sarah D. C. , Hof Liesbeth , Jonker Allert J. , Voorn Pieter 
Published: March 2003

AbstractRepeated exposure to drugs of abuse induces behavioural sensitization, i.e. a persistent hypersensitivity to the psychomotor stimulant effects of these drugs. This may be the result of increased responsiveness, to drugs, of mesostriatal dopamine systems and their projections, but it has also been suggested that acute and sensitized behavioural responses to psychostimulant drugs involve activation of distinct neuronal circuits. In order to distinguish between these possibilities, we studied amphetamine‐induced c‐fos immunoreactivity in subregions of rat striatum (patch and matrix compartments of caudate–putamen and nucleus accumbens core and shell) in drug‐naive rats, as well as during long‐term expression of amphetamine sensitization. We found that, in sensitized animals, amphetamine (1.0 mg/kg) evoked an increase in the ratio of c‐fos‐immunopositive cells in striatal patch and matrix compartments, suggesting a preferential involvement of striatal patches in the sensitized response to amphetamine. In drug‐naive rats, amphetamine (0.5–5.0 mg/kg) dose‐dependently increased c‐fos expression in all striatal subregions. Remarkably, the highest dose of amphetamine also evoked an increase in patch : matrix ratio of c‐fos immunoreactivity. In nucleus accumbens core and shell of amphetamine‐ and saline‐pretreated animals, amphetamine (1.0 mg/kg) evoked comparable increases in c‐fos expression. These data indicate that distinct striatal compartments display a differential sensitivity to amphetamine in both drug‐naive and amphetamine‐sensitized animals. In addition, they suggest that the shift in amphetamine‐induced c‐fos expression from striatal matrix to patches in sensitized animals is the consequence of a change in the sensitivity to amphetamine, rather than a long‐term circuitry reorganization that is exclusive to the sensitized state.
Calbindin neurons in the hamster suprachiasmatic nucleus do not exhibit a circadian variation in spontaneous firing rate
Authors: Jobst Erin E. , Allen Charles N. 
Published: March 2003

AbstractThe role of the mammalian suprachiasmatic nuclei (SCN) in generating circadian rhythms in behaviours and other physiological processes is well established. A prominent feature of SCN neurons is the circadian oscillation in action potential firing frequency, with a peak near midday. A subset of calbindin‐immunoreactive (CB+) neurons form a compact subnucleus (CBsn) in the hamster SCN. Restoration of rhythmicity using fetal SCN grafts in SCN‐lesioned hamsters is critically dependent upon the presence of CB+ neurons within the transplanted grafts [LeSauter & Silver (1999) J. Neurosci., 5574–5585]. The aim of the current study was to determine whether CB+ neurons within the CBsn of the hamster SCN fire action potentials in a circadian pattern as part of their output signal. Using patch‐clamp recording, we demonstrated that CB+ neurons in the CBsn do not express a circadian rhythm in spontaneous firing frequency under diurnal conditions in vitro. Furthermore, the percentage of silent CB– cells varies with zeitgeber time, whereas the percentage of silent CB+ cells does not. Immunohistochemical analysis revealed that the CBsn is a nonhomogeneous nucleus, containing many more CB– than CB+ cells. Our results reveal that CB+ neurons within the CBsn represent a functionally distinct neuronal subpopulation in which rhythmic action potential output may not be necessary for the restoration of behavioural circadian rhythmicity.
Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour
Authors: Berntson G. G. , Shafi R. , Sarter M. 
Published: March 2003

AbstractThe present study examined the role of the basal forebrain corticopetal cholinergic projection in the regulation of cortical electroencephalographic activity across sleep/wake states in rats. Selective lesions of this projection were effected by local intraparenchymal infusions of the immunotoxin 192 IgG‐saporin. Lesions spared the septo‐hippocampal cholinergic system, as well as p75‐receptor‐bearing noncholinergic neurons in the suprachiasmatic nucleus. Relative to sham‐lesioned control animals, rats with lesions of basal forebrain cholinergic neurons displayed a significant reduction in high frequency EEG activity, characterized especially by a reduction in gamma EEG power. Lesions did not significantly alter the overall proportion of sleeping and waking states as defined behaviourally, but the attenuation of high frequency EEG activity was apparent across all stages, including REM‐like periods. Results are consistent with the view that the basal forebrain corticopetal cholinergic system exerts a general activational effect on the cortical mantle. Although this system may not be essential for sleep/wake stage‐switching, it does impact on the cortical states associated with those stages.
Increased BDNF and trk‐B mRNA expression in cortical and limbic regions following formation of a social recognition memory
Authors: Broad Kevin D. , Mimmack Mike L. , Keverne E Barry , Kendrick Keith M. 
Published: March 2003

AbstractBrain‐derived neurotrophic factor (BDNF) and its receptor, tyrosine receptor kinase (trk‐B), play important roles in neural plasticity, long‐term potentiation and memory formation. Sheep form a selective recognition memory for their lambs within 2 h of birth. Initially, this memory is exclusively based on olfactory cues; however, as it consolidates over a 12‐h recognition period it extends to incorporate visual cues. We investigated whether changes in BDNF and trk‐B mRNA expression occurred in both olfactory and visual processing systems at 4.5 h postpartum, 2–3 h after the behavioural manifestations of an olfactory recognition memory were found. Animals that formed a recognition memory showed increased BDNF mRNA expression in the inferior part of the temporal cortex, subfield CA1 of the hippocampus, the diagonal band, basolateral amygdala and the anterior cingulate, medial frontal, entorhinal and pyriform cortices. No increases were observed in either the olfactory bulbs or the dentate gyrus. Expression of trk‐B mRNA was significantly increased only in the medial temporal, entorhinal and pyriform cortices. These findings demonstrate that by 2–3 h following the initial formation of olfactory recognition memory there are BDNF/trk‐B‐mediated plasticity changes in brain areas involved in the consolidation of olfactory memory (the pyriform and entorhinal cortices). However, similar changes also occur in areas of the brain involved in visual memory, face and object recognition (the temporal cortex, entorhinal cortex, hippocampal subfield CA1 and basolateral amygdala), and in areas of the brain with integrative and attentional functions (the medial frontal and anterior cingulate cortices and diagonal band). This suggests that reorganization of neural circuits underlying the visual recognition of lambs or the integration of olfactory/visual information is occurring even at this time even though accurate behavioural recognition at this stage can only be made using olfactory cues.
Spatial reconfiguration of charge transfer effectiveness in active bistable dendritic arborizations
Authors: Korogod S. M. , Kulagina I. B. , Kukushka V. I. , Gogan P. , Tyc‐Dumont . S. 
Published: March 2003

AbstractThe aim of this work was to explore the electrical spatial profile of the dendritic arborization during membrane potential oscillations of a bistable motoneuron. Computational simulations provided the spatial counterparts of the temporal dynamics of bistability and allowed simultaneous depiction the electrical states of any sites in the arborization. We assumed that the dendritic membrane had homogeneously distributed specific electrical properties and was equipped with a cocktail of passive extrasynaptic and NMDA synaptic conductances. The electrical conditions for evoking bistability in a single isopotential compartment and in a whole dendritic arborization were computed and showed differences, revealing a crucial effect of dendritic geometry. Snapshots of the whole arborization during bistability revealed the spatial distribution of the density of the transmembrane current generated at the synapses and the effectiveness of the current transfer from any dendritic site to the soma. These functional maps changed dynamically according to the phase of the oscillatory cycle. In the low depolarization state, the current density was low in the proximal dendrites and higher in the distal parts of the arborization while the transfer effectiveness varied in a narrow range with small differences between proximal and distal dendritic segments. When the neuron switched to high depolarization state, the current density was high in the proximal dendrites and low in the distal branches while a large domain of the dendritic field became electrically disconnected beyond 200 µm from the soma with a null transfer efficiency. These spatial reconfigurations affected dynamically the size and shape of the functional dendritic field and were strongly geometry‐dependent.