bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐localization of brain‐derived neurotrophic factor (BDNF) and wild‐type huntingtin in normal and quinolinic acid‐lesioned rat brain
Authors: Fusco Francesca R. , Zuccato Chiara , Tartari Marzia , Martorana Alessandro , De March Zena , Giampà Carmela , Cattaneo Elena , Bernardi Giorgio 
Published: September 2003

AbstractLoss of huntingtin‐mediated brain‐derived neurotrophic factor (BDNF) gene transcription has been described in Huntington's disease (HD) [Zuccato et al. (2001) Science, 293, 493–498]. It has been shown that BDNF is synthesized in the pyramidal layer of cerebral cortex and released in the striatum [Altar et al. (1997) Nature, 389, 856–860; Conner et al. (1997) J. Neurosci., 17, 2295–2313]. Here we show the cellular localization of BDNF in huntingtin‐containing neurons in normal rat brain; our double‐label immunofluorescence study shows that huntingtin and BDNF are co‐contained in ≈99% of pyramidal neurons of motor cortex. In the striatum, huntingtin is expressed in 75% of neurons containing BDNF. In normal striatum we also show that BDNF is contained in cholinergic and in NOS‐containing interneurons, which are relatively resistant to HD degeneration. Furthermore, we show a reduction in huntingtin and in BDNF immunoreactivity in cortical neurons after striatal excitotoxic lesion. Our data are confirmed by an ELISA study of BDNF and by a Western blot analysis of huntingtin in cortex of quinolic acid (QUIN)‐lesioned hemispheres. In the lesioned striatum we describe that the striatal subpopulation of cholinergic neurons, surviving degeneration, contain BDNF. The finding that BDNF is contained in nearly all neurons that contain huntingtin in the normal cortex, along with the reduced expression of BDNF after QUIN injection of the striatum, shows that huntingtin may be required for BDNF production in cortex.
Acute stress increases calcium current amplitude in rat hippocampus: temporal changes in physiology and gene expression
Authors: Joëls M. , Velzing E. , Nair S. , Verkuyl J. M. , Karst H. 
Published: September 2003

AbstractActivation of hippocampal glucocorticoid receptors in vitro increases calcium current amplitude through a process requiring DNA binding of receptor homodimers. We here investigated (i) whether similar increased calcium currents also occur following in vivo glucocorticoid receptor activation due to stress and (ii) if so, whether this can be explained by increased expression of calcium channel subunits. Rats were exposed to a novelty stress; some of the animals were pretreated with a glucocorticoid receptor antagonist. In subsequently prepared hippocampal slices, calcium currents were recorded from identified CA1 pyramidal neurons, after which RNA was collected, linearly amplified and hybridized with cDNA clones. Glucocorticoid receptor activation due to novelty exposure was associated with large total peak calcium currents and high‐threshold noninactivating currents. Low‐threshold calcium currents were not affected. Large total peak and noninactivating current amplitudes were also seen when animals received a more severe stressor, i.e. additional ether exposure. In the stressed groups, the total peak and high‐threshold calcium current gradually increased with time resulting in a significant enhancement at ≥3 h after stress exposure. In the same cells, the summated (relative) RNA expression of various α1 calcium channel subunits was only transiently enhanced, prior to the functional changes. These data indicate that in vivo activation of glucocorticoid receptors due to stress gradually increases specific calcium current components. Prior to the functional change, increased expression of calcium channel subunits was observed, suggesting that the enhanced function could be explained by transcriptional regulation of the channels.
Potent mammalian cerebroprotection and neuronal cell death inhibition are afforded by a synthetic antioxidant analogue of marine invertebrate cell protectant ovothiols
Authors: Vamecq Joseph , Maurois Pierre , Bac Pierre , Bailly Fabrice , Bernier Jean‐Luc , Stables James P. , Husson Isabelle , Gressens Pierre 
Published: September 2003

AbstractImplicit strategies for neuroprotection in the adult brain include GABAAreceptor activation,N‐methyl‐d‐aspartate receptor and sodium voltage‐gated channel inhibition. Ironically, these same targets may be harmful to the immature or developing brain. Protection has been demonstrated for both immature and mature brain with the use of a synthetic ovothiol analogue. The following beneficial effects have been demonstrated in mice: protection against audiogenic seizures, brain structures with clear‐cut delineation of ibotenate‐challenged white and grey matter lesions along with exceptional early and delayed protections, and potent cerebral cell death inhibition. The compound lacks both GABAergic activity and sodium channel blocker properties, which may help explain the lack of toxicity normally expressed in an immature brain utilizing these agents [J.W. Olney (2002) Neurotoxicology, 93, 1–10]. The oxidized form of the compound is virtually devoid of antioxidant activity.In vivoit exhibits cerebroprotective properties similar to those of reduced compounds endowed with antioxidant properties. This unexpected finding has prompted an extensivein vitroexploration of underlying molecular mechanisms that have led to the identification of several recycling mechanisms consistent with non rate‐limiting conversion of oxidized to reduced compound forms. Taken as a whole, this work offers an unique combinedin vitroandin vivosupport that: (i) antioxidant therapy, here engineered from marine invertebrate egg protectants, may be a valuable strategy in protecting both mammalian adult and developing brain; and (ii) recycling (thiol‐disulphide exchange) properties of the oxidized form of an antioxidant compound are as important as the antioxidant potential exhibited by a bioactive reduced antioxidant in certain neuroprotective processes.
Nicotine recruits a local glutamatergic circuit to excite septohippocampal GABAergic neurons
Authors: Wu Min , Hajszan Tibor , Leranth Csaba , Alreja Meenakshi 
Published: September 2003

AbstractTonic impulse flow in the septohippocampal GABAergic pathway is essential for normal cognitive functioning and is sustained, in part, by acetylcholine (ACh) that is released locally via axon collaterals of septohippocampal cholinergic neurons. Septohippocampal cholinergic neurons degenerate in Alzheimer's disease and other neurodegenerative disorders. While the importance of the muscarinic effects of ACh on septohippocampal GABAergic neurons is well recognized, the nicotinic effects of ACh remain unstudied despite the reported benefits of nicotine on cognitive functioning. In the present study, using electrophysiological recordings in a rat brain slice preparation, rapid applications of nicotine excited 90% of retrogradely labelled septohippocampal GABA‐type neurons with an EC50 of 17 µm and increased the frequency of spontaneously occurring, impulse‐dependent fast GABAergic and glutamatergic synaptic currents via the α4β2‐nicotinic receptor. Interestingly, tetrodotoxin blocked all effects of nicotine on septohippocampal GABAergic type neurons, suggesting involvement of indirect mechanisms. We demonstrate that the effects of nicotine on septohippocampal GABA‐type neurons involve recruitment of a novel, local glutamatergic circuitry as (i) Group I metabotropic glutamatergic receptor antagonists reduced the effects of nicotine; (ii) the number of nicotine responsive neurons was significantly reduced in recordings from slices that had been trimmed so as to reduce the number of glutamate‐containing neurons within the slice preparation; (iii) in light and ultrastructural double immunocytochemical labelling studies vesicular glutamate 2 transporter immunoreactive terminals made synaptic contacts with parvalbumin‐immunoreactive septohippocampal GABAergic neurons. The discovery of a local glutamatergic circuit within the septum may provide another avenue for restoring septohippocampal GABAergic functions in neurodegenerative disorders associated with a loss of septohippocampal cholinergic neurons.
Release of BDNF and GABA in the dorsal horn of neuropathic rats
Authors: Lever Isobel , Cunningham Joanna , Grist John , Yip Ping K. , Malcangio Marzia 
Published: September 2003

AbstractDamage to peripheral nerves is associated with changes in excitability and/or phenotype of primary afferent neurons as well as increased neuronal excitability (central sensitization) and reduced inhibitory tone in the dorsal horn. For instance, in dorsal root ganglia (DRG) brain derived neurotrophic factor (BDNF) is down‐regulated in small cells whilst de novo expressed in large diameter cells. In the dorsal horn, GABA content is decreased. In this study, in a dorsal horn, ‘with dorsal roots attached’ preparation obtained from spinal nerve lesioned Wistar rats, stimulation of ipsilateral dorsal roots at either A fibre or A + C fibre strength did not evoke release of BDNF. In separate experiments, activity‐induced release of GABA in the isolated dorsal horn of neuropathic rats was significantly reduced compared to release in sham operated rats. GABA release could be significantly restored following topical application of BDNF through the dorsal horn preparation. Finally, neuropathic rats developed thermal and mechanical hypersensitivity and thermal hyperalgesia was reduced by intrathecal injection of BDNF. We concluded that BDNF‐induced release of GABA could be a mechanism to explain the antinociceptive action of intrathecal BDNF in neuropathic animals. Furthermore, reduced availability of sensory neuron‐derived BDNF might contribute to the reduced GABAergic tone in the dorsal horn of neuropathic rats.
Dopamine efflux in nucleus accumbens shell and core in response to appetitive classical conditioning
Authors: Cheng J. J. , De Bruin J. P. C. , Feenstra M. G. P. 
Published: September 2003

AbstractDopamine transmission within the nucleus accumbens has been implicated in associative reinforcement learning. We investigated the effect of appetitive classical conditioning on dopamine efflux in the rat nucleus accumbens shell and core, as dopamine may be differentially activated by conditioned and unconditioned stimuli (CS, US) in these subregions. After implantation of microdialysis cannulae, rats were food restricted and trained for three consecutive days with three acquisition sessions per day. A 10‐s noise (CS) was immediately followed by the delivery of two reward pellets (US) for the conditioned group (paired presentation), whereas conditioned stimuli and unconditioned stimuli were presented at random for the control group (unpaired presentation). On the fourth day, all rats were given a further CS + US session and two CS‐alone sessions, and extracellular dopamine concentrations were measured (7.5 min/per sample). Behavioural measures (number of nose pokes, latency to nose poke after conditioned stimuli onset, locomotor activity) demonstrated that the paired groups showed a high level of conditioning. CS + US presentation increased dopamine equally in both shell and core of the paired and unpaired groups. CS alone presentation induced a conditioned dopamine release only in the paired groups. No significant difference was found between shell and core. Unlike previous conditioning paradigms involving either a more salient US (foot shock, addictive drug) or a more complex CS, the present paradigm, using normal reward pellets as US and a discrete auditory stimulus as CS, did not lead to differential responses in dopamine efflux in shell and core subregions of the nucleus accumbens.
Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation
Authors: Law Amanda J. , Weickert Cynthia Shannon , Webster Maree J. , Herman Mary M. , Kleinman Joel E. , Harrison Paul J. 
Published: September 2003

AbstractThe N‐methyl‐d‐aspartate receptor plays a critical role in the formation and maintenance of synapses during brain development. In the rodent, changes in subunit expression and assembly of the heteromeric receptor complex accompany these maturational processes. However, little is known about N‐methyl‐d‐aspartate receptor subunit expression during human brain development. We used in situ hybridization to examine the distribution and relative abundance of NR1, NR2A and NR2B subunit messenger ribonucleic acids in the hippocampal formation and adjacent cortex of 34 human subjects at five stages of life (neonate, infant, adolescent, young adult and adult). At all ages, the three messenger ribonucleic acids were expressed in all subfields, predominantly by pyramidal neurons, granule cells and polymorphic hilar cells. However, their abundance varied across ontogeny. Levels of NR1 messenger ribonucleic acid in CA4, CA3 and CA2 subfields were significantly lower in the neonate than all other age groups. In the dentate gyrus, subiculum and parahippocampal gyrus, NR2B messenger ribonucleic acid levels were higher in the neonate than in older age groups. NR2A messenger ribonucleic acid levels remained constant, leading to an age‐related increase in NR2A/2B transcript ratio. We conclude that N‐methyl‐d‐aspartate receptor subunit messenger ribonucleic acids are differentially expressed during postnatal development of the human hippocampus, with a pattern similar but not identical to that seen in the rodent. Changes in subunit composition may thus contribute to maturational differences in human hippocampal N‐methyl‐d‐aspartate receptor function, and to their role in the pathophysiology of schizophrenia and other neurodevelopmental disorders.
Post‐natal development of type 1 cannabinoid receptor immunoreactivity in the rat hippocampus
Authors: Morozov Yury M. , F. Freund Tamás 
Published: September 2003

AbstractType 1 cannabinoid receptors, selectively located on axon terminals of GABAergic interneurons in the hippocampus, are known to be involved in endocannabinoid‐mediated retrograde synaptic signalling. The question arises whether type 1 cannabinoid receptors appear on these axons during early post‐natal life, when GABAergic transmission is still depolarizing, and whether there are any developmental changes in the cellular or subcellular expression pattern. Here we demonstrate, using single and double immunocytochemical methods at the light and electron microscopic levels, that type 1 cannabinoid receptors are expressed only on the membrane of axon terminals and pre‐terminal axons but not on the soma‐dendritic membrane at all examined timepoints between post‐natal days 0 and 20, similar to the adult distribution. All type 1 cannabinoid receptor‐positive boutons formed symmetric synapses. Granular labelling in the somata was already strong at post‐natal day 0 and corresponded to multivesicular bodies, lysosomes, Golgi apparatus and rough endoplasmic reticulum. The type 1 cannabinoid receptor‐positive axons were shown to originate largely from cholecystokinin‐immunoreactive basket and bistratified neurons throughout the hippocampus (90% of all type 1 cannabinoid receptor‐containing cells) and dentate gyrus (70% of all type 1 cannabinoid receptor‐containing cells). The remaining cells have not been identified but probably belong to the somatostatin‐ and/or neuropeptide Y‐containing subsets, as cholecystokinin‐negative, type 1 cannabinoid receptor‐positive axons have been observed in strata moleculare and lacunosum‐moleculare of the dentate gyrus and CA1–3, respectively, where these neurons are known to arborize. No cell types were found that expressed type 1 cannabinoid receptors transiently at some developmental stage. We conclude that the cellular and subcellular pattern of type 1 cannabinoid receptor expression during early post‐natal life is similar to the adult pattern and type 1 cannabinoid receptors are expressed on the cholecystokinin‐containing axons as soon as synapse formation begins. This suggests that retrograde synaptic signalling by endocannabinoids is required for the normal operation of GABAergic neurotransmission even before it becomes hyperpolarizing.
Spatial channels of visual processing in cortical blindness
Authors: Sahraie Arash , Trevethan Ceri T. , Weiskrantz Lawrence , Olson John , MacLeod Mary Joan , Murray Alison D. , Dijkhuizen Roelf S. , Counsell Carl , Coleman Richard 
Published: September 2003

AbstractBlindsight is the ability of some cortically blind patients to discriminate visual events presented within their field defect. We have examined a fundamental aspect of visual processing, namely the detection of spatial structures presented within the field defect of 10 cortically blind patients. The method outlined is based on the detection of high‐contrast stimuli and is effective in flagging a ‘window of detection’ in the spatial frequency spectrum, should it exist. Here we report on the presence of a narrowly tuned psychophysical spatial channel optimally responding to frequencies less than 4 cycles/° in eight out of 10 patients tested. The two patients who did not show any evidence of blindsight appear to have intact midbrain structures, but have lesions that extend from the occipital cortex to the thalamus. In addition, we have recorded subjective reports of awareness of the visual events in each trial. Detection scores of eight blindsight patients were subsequently subdivided based on the subjective reports of awareness. It appears that the psychophysical spatial channel‐mediating responses in the absence of any awareness of the visual event have a narrower frequency response than those involved when the patients report some awareness of the visual event. The findings are discussed in relation to previous reports on the incidence of blindsight and performance on tasks involving spatial processing.
Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear
Authors: Pissiota Anna , Frans Örjan , Michelgård Åsa , Appel Lieuwe , Långström Bengt , Flaten Magne Arve , Fredrikson Mats 
Published: September 2003

AbstractThe human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with15O‐water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non‐feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non‐phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non‐phobic startle vs. non‐phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid–hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co‐activation of these areas may reflect increased attention to fear‐relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect.
Cyclic AMP response element‐binding (CREB)‐like proteins in a molluscan brain: cellular localization and learning‐induced phosphorylation
Authors: Ribeiro Maria J. , Serfőző Zoltán , Papp Andrea , Kemenes Ildikó , O'Shea Michael , Yin Jerry C. P. , Benjamin Paul R. , Kemenes György 
Published: September 2003

AbstractThe phosphorylation and the binding to DNA of the nuclear transcription factor, cyclic adenosine 3′,5′‐monophosphate (cAMP) response element‐binding protein (CREB) are conserved key steps in the molecular cascade leading to the formation of long‐term memory (LTM). Here, we characterize, for the first time, a CREB1‐like protein in the central nervous system (CNS) of Lymnaea, a model system used widely for the study of the fundamental mechanisms of learning and memory. We demonstrate cAMP response element (CRE)‐binding activity in CNS protein extracts and show that one of the CRE‐binding proteins is recognized by a polyclonal antibody raised to mammalian (human) CREB1. The same antibody detects specific CREB1 immunoreactivity in CNS extracts and in the nuclei of most neurons in the brain. Moreover, phospho–CREB1‐specific immunoreactivity is increased significantly in protein extracts of the CNS by forskolin, an activator of adenylate cyclase. The forskolin‐induced increase in phospho–CREB1 immunoreactivity is localized to the nuclei of CNS neurons, some of which have an important role in the formation of LTM. Significantly, classical food–reward conditioning increases phospho–CREB1 immunoreactivity in Lymnaea CNS protein extracts. This increase in immunoreactivity is specific to the ganglia that contain the feeding circuitry, which undergoes cellular changes after classical conditioning. This work establishes the expression of a highly conserved functional CREB1‐like protein in the CNS of Lymnaea and opens the way for a detailed analysis of the role of CREB proteins in LTM formation in this model system.
Modulation of electroencephalographic responses to transcranial magnetic stimulation: evidence for changes in cortical excitability related to movement
Authors: Nikulin Vadim V. , Kičić Dubravko , Kähkönen Seppo , Ilmoniemi Risto J. 
Published: September 2003

AbstractTranscranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) were used for the investigation of cortical excitability preceding voluntary movement in human subjects. The study showed the practical value of the combined TMS–EEG approach in differentiating between cortical and spinal‐cord mechanisms, which is difficult with conventional electromyographic measures alone. TMS induced a pronounced negativity (N100) lasting for 150–200 ms, with the amplitude maximum in the stimulated hemisphere. When TMS was applied just before the onset of the visually triggered movement, N100 was markedly attenuated, although motor evoked potentials (MEPs) became larger. We suggest that the N100 component represents an inhibitory response following TMS. This interpretation is in agreement with intracellular recordings in animals, paired‐pulse TMS studies and experiments showing increased premovement excitability on the basis of MEPs. N100 was not affected only by the subsequent movement, but also by the switching from rest to the motor‐task condition, which caused a slight attenuation of the N100 component; no changes, however, were found in the amplitude of MEPs, suggesting that modified excitability did not affect the output of the corticospinal pyramidal cells. By contrast to MEPs, N100 was modulated also by the presentation of the visual stimulus alone, i.e. when no movement was required. This attenuation suggests that even in a rest condition visual stimuli have an access to the sensorimotor regions of the cortex, most probably through ascending arousal brain systems.