bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Damage to Auditory Neurons and Hair Cells by Ototoxins and Neuroprotection by Specific Neurotrophins in Rat Cochlear Organotypic Cultures
Authors: Zheng J. Lisa , Gao Wei‐Qiang 
Published: April 2006

AbstractTherapeutic ototoxic drugs are one of the major causes of damage in the peripheral auditory system, leading to hearing loss. In this study, we have examined the toxic actions of three classes of ototoxins (sodium salicylate, gentamicin and cisplatin) in organotypic cultures of postnatal cochlear explants. In these cultures, afferent innervation of hair cells by primary auditory neurons remained intact. Double labelling with a monoclonal antibody against neurofilament protein and a phalloidin‐fluorescein isothiocyanate conjugate revealed that the three types of drugs induced differential damage to auditory neurons and hair cells in the cochlea. While gentamicin preferentially caused hair cell death, sodium salicylate specifically induced degeneration of auditory neurons. In contrast, cisplatin resulted in destruction of both auditory neurons and hair cells. Neuronal degeneration was largely prevented by the addition of neurotrophin‐4/5, brain‐derived neurotrophic factor and neurotrophin‐3 to the culture media together with the ototoxins, while nerve growth factor and other growth factors had no effect. In contrast, the hair cell loss caused by cisplatin or gentamicin was not attenuated by the presence of neurotrophins. These results suggest that ototoxic mechanisms of salicylates, aminoglycosides and chemotherapeutic agents are different. Auditory neuronal loss induced by ototoxins may be prevented by specific neurotrophins.
Phenotype of Striatal Cells Expressing c‐Fos Following Amphetamine Treatment of Rats with Intrastriatal Dopaminergic Grafts
Authors: Abrous D. N. , Bernard V. , Le Moal M. , Bloch B. , Herman J. P. 
Published: April 2006

AbstractActivation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c‐Fos expression in the striatum, mostly in the striatonigral substance P‐ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c‐Fos is greatly increased in the graft‐bearing striatum compared with the normal striatum. We examined whether this increase in the number of c‐Fos‐expressing neurons corresponds to the recruitment of a new neuronal population, or whether it reflects an increase in the proportion of substance P‐ergic neurons exhibiting activation of c‐Fos. Adult rats received a unilateral 6‐hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d‐amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c‐Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c‐Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti‐c‐Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c‐Fos following amphetamine treatment. The density of neurons expressing c‐Fos following amphetamine treatment was three‐fold higher in the graft‐bearing striata than in the striata of control animals. Approximately 75% of the c‐Fos expressing cells were substance P‐ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y‐ergic or cholinergic. Similar proportions were found in the graft‐bearing striatum, signifying that the pattern of activation of c‐Fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c‐Fos predominantly reflects a graft‐induced increase in the proportion of neurons expressing c‐Fos within the same population of neurons which normally expresses c‐Fos in the striatum, i.e. the striatonigral substance P‐ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P‐ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine‐induced stimulation of the implanted dopaminergic neurons.
Synapsin‐like Molecules in Aplysia punctata and Helix pomatia: Identification and Distribution in the Nervous System and During the Formation of Synaptic Contacts In Vitro
Authors: Cibelli Giuseppe , Ghirardi Mirella , Onofri Franco , Casadio Andrea , Benfenati Fabio , Montarolo Pier Giorgio , Vitiello Francesco 
Published: April 2006

AbstractThe distribution and biochemical features of the synapsin‐like peptides recognized in Aplysia and Helix by various antibodies directed against mammalian synapsins were studied. The peptides can be extracted at low pH and are digested by collagenase; further, they can be phosphorylated by both protein kinase A and Ca2+/calmodulin‐dependent protein kinase II. In the ganglia of both snails, they are associated with the soma of most neurons and with the neuropil; punctate immunostaining is present along the neurites. Using cocultures of a Helix serotoninergic neuron and of its target cell, we analysed the redistribution of the synapsin‐like peptides during the formation of active synaptic contacts. When the presynaptic neuron is plated in isolation, both synapsin and serotonin immunoreactivities are restricted to the distal axonal segments and to the growth cones; in the presence of the target, the formation of a chemical connection is accompanied by redistribution of the synapsin and serotonin immunoreactivities that concentrate in highly fluorescent round spots scattered along the newly grown neurites located close to the target cell. Almost every spot that is stained for serotonin is also positive for synapsin. In the presynaptic cell plated alone, the number of these varicosity‐like structures is substantially stable throughout the whole period; by contrast, when the presynaptic cell synapses the target, their number increases progressively parallel to the increase in the mean amplitude of cumulative excitatory postsynaptic potentials recorded at the same times. The data indicate that mollusc synapsin‐like peptides to some extent resemble their mammalian homologues, although they are not exclusively localized in nerve terminals and their expression strongly correlates with the formation of active synaptic contacts.
Effects of High Helium Pressure on Intracellular and Field Potential Responses in the CA1 Region of the In Vitro Rat Hippocampus
Authors: Southan A. P. , Wann K. T. 
Published: April 2006

AbstractWe have investigated the effects of high helium pressure (up to 13.3 MPa) on the electrophysiological responses of CA1 neurons in rat hippocampal slices using a purpose built pressure chamber, designed to facilitate field potential and intracellular recording. In field potential experiments, near threshold orthodromic responses were depressed by modest pressure (0.4 MPa). At higher stimulus intensities, orthodromic and antidromic population spike amplitudes were not increased at 5 MPa but were significantly enhanced at 10 MPa, and multiple population spikes were observed in some experiments. Orthodromic paired pulse potentiation was not affected by pressure up to 10 MPa. In intracellular experiments there were no significant differences between mean values obtained for resting membrane potential and input resistance at atmospheric pressure and pressures of up to 10 MPa. However, spontaneous depolarizing membrane potential excursions, decreased slow after‐hyperpolarization responses and reduced accommodation properties were observed at pressure (5–10 MPa). One possibility is that the SK and M potassium channel systems may be more sensitive to high pressure than other membrane ion channels. These effects may contribute towards the high pressure neurological syndrome observed in vivo.
7‐OH‐DPAT Differentially Reverses Clozapine‐ and Haloperidol‐induced Increases in Fos‐like Immunoreactivity in the Rodent Forebrain
Authors: Vahid‐Ansari F. , Robertson G. S. 
Published: April 2006

AbstractThe pattern of neurons which display haloperidol‐induced Fos‐like immunoreactivity closely matches the distribution of striatal D2 dopamine receptors, whereas clozapine‐induced Fos‐like immunoreactivity occurs primarily in regions that contain high levels of the D3 dopamine receptor. These neuroanatomical correlations suggest that haloperidol and clozapine may elevate Fos‐like immunoreactivity by blocking D2 and D3 receptors respectively. In order to test this hypothesis, the abilities of prior administration of the D3 receptor‐preferring agonist 7–hydroxy‐N, N′‐di‐n‐propyl‐2‐aminotetraline (7–OH‐DPAT) to competitively reverse haloperidol‐ and clozapine‐induced increases in Fos‐like immunoreactivity were compared. Administration of 7–OH‐DPAT (0.05 mg/kg, s.c.) 30 min before clozapine (20 mg/kg, s.c.) produced a 60% reduction in the number of neurons that displayed clozapine‐induced Fos‐like immunoreactivity in the major island of Calleja, nucleus accumbens and medial aspect of the striatum, while prior administration of 0.5 mg/kg (s.c.) of 7‐OH‐DPAT completely reversed these increases in Fos‐like immunoreactivity. In contrast, the increases in Fos‐like immunoreactivity in the major island of Calleja, nucleus accumbens and striatum (medial and dorsal aspects) induced by haloperidol (0.1 mg/kg, s.c.) were only reduced by the high dose of 7‐OH‐DPAT (0.5 mg/kg, s.c.). Hence, clozapine‐induced increases in Fos‐like immunoreactivity were more readily reversed by 7‐OH‐DPAT than elevations in Fos‐like immunoreactivity produced by haloperidol. These results suggest that D3 receptor blockade plays a larger role in mediating clozapine‐ than haloperidol‐induced increases in Fos‐like immunoreactivity.
Altered Gene Expression of the N‐Methyl‐d‐Aspartate Receptor Channel Subunits in Purkinje Cells of the Staggerer Mutant Mouse
Authors: Nakagawa Shin , Watanabe Masahiko , Inoue Yoshiro 
Published: April 2006

AbstractThe gene expression of five NMDA receptor channel subunits, the ɛ1 ɛ2, epsiv;3, ɛ4 and ζ1 subunits, was examined in cerebellar Purkinje cells of the staggerer mouse at postnatal day 21. In the midline region of the staggerer cerebellum, signals for the ɛ1, ɛ4, and ζ1 subunit mRNAs were distributed in Purkinje cells, which have a large cell body aligned in a monolayer between the granular and molecular layers. In addition to the midline region, labelled neurons in the intermediate cerebellar region were, though at lower levels, aligned almost in a monolayer between the granular and molecular layers. In the hemisphere, most labelled neurons occurred in various locations in the granular layer and the cerebellar medulla. These regions, populated with Purkinje cells expressing the ɛl, ɛ4, and ζ1 subunit mRNAs, were separated from each other by narrow gap regions that contained neurons without any detectable NMDA receptor channel subunit mRNAs. These results suggest that there is discrete mediolateral heterogeneity in staggerer Purkinje cell populations, in terms of expression properties of the NMDA receptor channel subunits. When compared with wild‐type Purkinje cells that express the ζ1 subunit alone, additional expression of the E subunits presumably explains the persistence of NMDA responses in adult staggerer Purkinje cells (Dupont et al Neuroscience, 12, 613‐619, 1984).
Injury‐induced Synthesis and Release of Apolipoprotein E and Clusterin from Rat Neural Cells
Authors: Messmer‐Joudrier S. , Sagot Y. , Mattenberger L. , James R. W. , Kato A. C. 
Published: April 2006

AbstractApolipoproteins in the brain have assumed major clinical importance since it was shown that one of the allelic forms of apolipoprotein E, apoE‐4, is a risk factor for Alzheimer's disease. Using tissue culture of embryonic rat spinal cord, we examined the effect of neuronal injury on the up‐regulation of two s apolipoproteins, apolipoprotein E and clusterin (apoJ). In order to study the influence of neuronal cells, we exploited the specific neurotoxic effect of elevated glutamate on these cells. Overstimulation by excess glutamate induced neuronal degeneration as assessed by morphological and biochemical criteria, notably the activity of choline acetyltransferase, which serves as a marker for cholinergic neurons. High concentrations of glutamate increased mRNA synthesis and the production and secretion of both apolipoprotein E and clusterin protein. Both neuronal cell death and release of the peptides were calcium‐dependent and could be blocked by the NMDA receptor antagonist MK‐801. Immunohistochemical data revealed the presence of clusterin in both neuronal and non‐neuronal cells whereas apolipoprotein E was mainly expressed in non‐neuronal cells. The results are suggestive of concerted up‐regulation of apolipoprotein E and clusterin when neural cells are subjected to injury.
Postsynaptic Currents and Short‐term Synaptic Plasticity in Purkinje Cells Grafted onto an Uninjured Adult Cerebellar Cortex
Authors: Tempia Filippo , Bravin Monica , Strata Piergiorgio 
Published: April 2006

AbstractIt has been shown recently that embryonic Purkinje cells grafted extraparenchymally into an intact cerebellum, in the absence of any sign of damage, are able to migrate into the host molecular layer where they receive a climbing fibre innervation. Using the same technique, we investigated the development of the electrophysiological properties of the synapses between the grafted cells and their main afferents. Purkinje cells either in the graft or having migrated into the molecular layer of the host were recorded using the whole‐cell patch‐clamp method in acutely prepared slices 17–112 days after grafting. Spontaneous postsynaptic currents with a single‐exponential decay and mediated by GABAA receptors were very similar to those described in normal Purkinje cells. Excitatory postsynaptic currents (EPSCs) evoked by climbing fibre and by parallel fibre stimulation were blocked by an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA)/kainate antagonist, and displayed the linear current‐voltage relation typical of postnatal Purkinje cells. The attainment of normal functional properties by the adult axons at the newly formed synaptic sites was shown by the expression of short‐term facilitation of parallel fibre EPSCs and of short‐term depression of climbing fibre EPSCs. The grafted Purkinje cells showed climbing fibre polyinnervation 17‐20 days after grafting which evolved to monoinnervation at 23‐45 days, confirming the completion of the developmental programme up to maturation. Our experiments support the view that the adult intact brain is able to accept and integrate an additional number of neurons which show fully mature electrophysiological properties which are electrophysiologically indistinguishable from those of the host neurons.
Status Epilepticus Causes Selective Regional Damage and Loss of GABAergic Neurons in the Rat Amygdaloid Complex
Authors: Tuunanen Jarkko , Halonen Toivo , Pitkänen Asla 
Published: April 2006

AbstractIn human epilepsy, the amygdala is often a primary focus for seizures. To analyse the status epilepticus‐induced alterations in the amygdaloid circuitries which may later underlie epileptogenesis, we studied the amygdaloid damage in kainic acid and perforant pathway stimulation models of status epilepticus in the rat. We also studied the damage to inhibitory GABAergic neurons. In both models, the medial division of the lateral nucleus, the parvicellular division of the basal nucleus and portions of the anterior cortical and medial nuclei were damaged. In the kainate model, where the seizure activity was more severe, the accessory basal nucleus, amygdalohippocampal area, posterior cortical nucleus and periamygdaloid cortex were also damaged. Two weeks after kainate‐induced seizures, 56% of the GABA‐immunoreactive neurons remained in the lateral nucleus (P < 0.05) and 25% in the basal nucleus (P < 0.01). Further analysis showed that one subpopulation of damaged GABAergic neurons was immunoreactive for somatostatin (48% remaining in the lateral nucleus, P < 0.01; 33% in the basal nucleus, P < 0.01). In the perforant pathway stimulation model, the damage to somatostatin neurons was milder. According to our data, the initial insult, such as status epilepticus, selectively damages amygdaloid nuclei. The loss of inhibition may underlie the spontaneous generation of seizures and epileptogenesis. On the other hand, many amygdaloid output nuclei (magnocellular and intermediate division of the basal nucleus, the central nucleus) remained relatively undamaged, providing pathways for seizure spread and generation of seizure‐related behavioural manifestations such as motor convulsions and fear response.
Micro‐Organization of Olivocerebellar and Corticonuclear Connections of the Paravermal Cerebellum in the Cat
Authors: Garwicz M. , Apps R. , Trott J. R. 
Published: April 2006

AbstractThe olivocerebellar and corticonuclear connections of the forelimb area of the paravermal medial C3 zone were studied in the cat using a combined electrophysiological and fluorescent tracer technique. During an initial operation under barbiturate anaesthesia, lobules IV/V of the cerebellar anterior lobe were exposed and small injections of dextran amines tagged with rhodamine or fluorescein were made into areas selected from four different electrophysiologically defined parts of the zone. The inferior olive and the deep cerebellar nuclei were then scrutinized for retrogradely labelled cells and anterogradely labelled axon terminals respectively. The findings demonstrate a detailed topographical organization within the olivocerebellar projection to the medial C3 zone and provide some evidence for a topographical organization of its projection to nucleus interpositus anterior. Both projections are described at a level of resolution not previously attained in neuroanatomical studies and the results strongly support the notion of a micro‐compartmentalization of cerebellar olivo‐corticonuclear circuits.
Dystroglycan in the Cerebellum is a Laminin α2‐chain Binding Protein at the Glial‐Vascular Interface and is Expressed in Purkinje cells
Authors: Tian M. , Jacobson C. , Gee S. H. , Campbell K. P. , Carbonetto S. , Jucker M. 
Published: April 2006

AbstractDystroglycan is a core component of the dystrophin receptor complex in skeletal muscle which links the extracellular matrix to the muscle cytoskeleton. Dystrophin, dystrophin‐related protein (DRP, utrophin) and dystroglycan are present not only in muscles but also in the brain. Dystrophin is expressed in certain neuronal populations while DRP is associated with perivascular astrocytes. To gain insights into the function and molecular interactions of dystroglycan in the brain, we examined the localization of α‐and β‐dystroglycan at the cellular and subcellular levels in the rat cerebellum. In blood vessels, we find a‐dystroglycan associated with the laminin a2‐chain‐rich parenchymal vascular basement membrane and β‐dystroglycan associated with the endfeet of perivascular astrocytes. We also show that a‐dystroglycan purified from the brain binds a2‐chain‐containing laminin‐2. These observations suggest a dystroglycan‐mediated linkage between DRP in perivascular astrocytic endfeet and laminin‐2 in the parenchymal basement membrane similar to that described in skeletal muscle. This linkage of the astrocytic endfeet to the vascular basement membrane is likely to be important for blood vessel formation and stabilization and for maintaining the integrity of the blood‐brain barrier. In addition to blood vessel labelling, we show that β‐dystroglycan in the rat cerebellum is associated with the surface of Purkinje cell bodies, dendrites and dendritic spines. Dystrophin has previously been localized to the inner surface of the plasma membrane of Purkinje cells and is enriched at postsynaptic sites. Thus, the present results also support the hypothesis that dystrophin interacts with dystroglycan in cerebellar Purkinje neurons.
Muscarinic Inhibition of Glutamatergic Transmission onto Rat Magnocellular Basal Forebrain Neurons in a Thin‐slice Preparation
Authors: Sim J. A. , Griffith W. H. 
Published: April 2006

AbstractWe have examined excitatory and inhibitory transmission in visually identified rat magnocellular basal forebrain neurons using whole‐cell patch‐clamp recordings in a thin‐slice preparation of the rat brain. In most cells, spontaneous excitatory and inhibitory synaptic activities could be recorded from their resting membrane potential. Following focal stimulation within the basal forebrain nucleus or directly onto visualized neighbouring neurons, postsynaptic currents were elicited in magnocellular basal forebrain cells held at ‐70 mV (a value close to their resting membrane potential). The synaptic responses were complex, consisting either mainly of excitatory postsynaptic currents (EPSCs), or inhibitory postsynaptic currents (IPSCs), or an EPSC‐IPSC sequence. The EPSC component was consistent with the activation of AMPA/KA receptors, as it could be selectively blocked by CNQX. The IPSC component resulted in the activation of GABAA receptors, and could be blocked by bicuculline. Since GABA‐mediated transmissions were not frequently recorded, we focused on the glutamate‐mediated transmission. Studies using specific calcium channel blockers suggested that both ω‐conotoxin GVIA‐sensitive and ω‐agatoxin VIA‐sensitive calcium channels contribute to the glutamatergic transmission onto magnocellular basal forebrain neurons. Carbachol (0.3–30 μM) had no observable effect on holding current, but produced a dose‐dependent inhibition of the amplitude of evoked EPSCs. This cholinergic modulation was mediated by muscarinic receptors, as it could be antagonized by atropine. The inhibitory effect of carbachol on the amplitude of EPSCs could be significantly antagonized by 100 nM methoctramine, an M2‐receptor antagonist. In contrast, only a small degree of antagonism could be obtained with pirenzepine, an M1‐muscarinic receptor antagonist, when present at relatively high concentration of 1 μM. Moreover, the action of carbachol was presynaptic, since the frequency of miniature postsynaptic currents was reduced without affecting their amplitude. In conclusion, the present findings indicate that glutamate‐mediated transmission onto magnocellular basal forebrain neurons appeared to involve both N‐ and P/Q‐type calcium channels, and that muscarinic modulation of glutamatergic transmission to MBF neurons is mediated by a presynaptic M2‐muscarinic receptor subtypes.