bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ion Dependence and Receptor Mediation of Glutamate Toxicity in the Immature Rat Hippocampal Slice
Authors: Lehmann Anders , Jacobson Ingemar 
Published: April 2006

AbstractGlutamate (glu) is a major excitatory transmitter and a toxin in the brain. In the present study, the immature rat hippocampal slice was used to determine the morphology, topography, ionic mediation and receptor specificity of glu toxicity. Slices were exposed to glu for 30 min, and the damage was evaluated after 3 h of recovery in regular medium. The effects on glu toxicity of changes of [Ca2+], [Cl‐] and [Na+] were determined. The receptor preference of glu was assessed by using the N‐methyl‐D‐aspartate (NMDA) antagonist MK‐801 and the kainate (KA)/quisqualate (QA) antagonist DNQX, alone or in combination. Further, to see whether glu produces cytotoxicity via osmolysis, the effects of hyperosmolal sucrose on glu toxicity were studied. Glu toxicity was similar to the previously described NMDA toxicity with regard to cytopathology, but differed in some aspects from that caused by KA and QA. The severity of the lesion was determined by the proximity of neurons to the incubation fluid, probably as a consequence of cellular accumulation of the amino acid. Omission of Ca2+ abolished glu toxicity in all neurons except the granule cells of the outer blade. This population was completely protected when Ca2+ was omitted and [Cl‐] was reduced. Elevation of [Ca2+] markedly aggravated the lesion caused by glu. Substitution of isethionate for Cl‐ worsened the glu‐induced damage, whilst the amino acid produced qualitatively different neuropathology when choline substituted for Na+. Apparently glu did not damage hippocampal nerve cells through an osmolytic mechanism as medium supplemented with 100 mM sucrose increased the toxicity of glu. Since the lesion produced by glu was more widespread in the presence of high [Ca2+], the effects of receptor antagonists were studied under this condition. MK‐801 inhibited glu toxicity whereas DNQX had no effect. Combination of MK‐801 and DNQX did not offer better protection than did MK‐801 alone. The results suggest that Ca2+ is the main (but not single) determinant of glu toxicity in the immature hippocampal slice. The ionic requirements of glu neurotoxicity are identical to those of NMDA, but differ from those of KA and QA. The notion that glu is a selective NMDA agonist in the present model was confirmed by the protection of MK‐801, and by the lack of an effect of DNQX. This is the first report demonstrating that the toxicity of glu is mediated by NMDA receptors in brain tissue which has developed normally. The findings indicate that specific blockade of NMDA receptors may be the most rational strategy in the prevention of glu‐related neuronal death occurring in certain neurological anomalies.
Activity‐Dependent Changes in Rat Ventral Horn Neurons in vitro; Summation of Prolonged Afferent Evoked Postsynaptic Depolarizations Produce a D‐2‐Amino‐5‐Phosphonovaleric Acid Sensitive Windup
Authors: Thompson S. W. N. , King A. E. , Woolf C. J. 
Published: April 2006

AbstractThe synaptic responses of lumbar ventral horn neurons including identified flexor motoneurons, to graded stimulation of peripheral nerves have been recorded in vitro in the young rat spinal cord‐hindlimb preparation. Single shock stimulation of low threshold myelinated afferents evoked short latency (< 20 ms) short duration (<1.0 s, 391 ± 42 ms n = 43 SEM) compositive mono‐ and polysynaptic potentials. Recruitment of both thinly myelinated (A delta) and unmyelinated (C) afferent fibres elicited a prolonged postsynaptic depolarization (> 1 s) in all cells. In the majority of cells (67.4%), this depolarization exceeded 4.0 s in duration (8.01 ± 0.4 s, n = 26, maximum 14 s). In the remainder, shorter responses were evoked (< 3.0 s, mean = 1.74 ± 0.4 s, n = 18). In those cells where the postsynaptic response to a single A delta or C fibre strength stimulus exceeded 4 s, low frequency (0.5–1.0 Hz) repetitive stimulation resulted in a temporal summation of the postsynaptic depolarizations, which generated a cumulatively increasing depolarization. This incrementing depolarization was sufficient in 33% of the cells to produce a progressive increase in spike discharge (windup). On cessation of the train of stimuli the depolarization decayed slowly (65 ± 27 s). The N‐methyl D‐aspartic acid (NMDA) receptor antagonist D‐2‐amino‐5‐phosphonovaleric acid (d‐APV) reduced the duration and amplitude of the prolonged postsynaptic depolarizations elicited by a single shock stimulation of small diameter afferents by 57% and 50% respectively. A smaller effect was produced on the low threshold afferent evoked early excitatory postsynaptic potentials (EPSP) (3% decrease in amplitude and 24% decrease in duration). In the presence of d‐APV the cumulatively incrementing depolarization produced by repetitive stimulation was substantially reduced and windup failed to occur. Activity‐dependent amplifications of primary afferent evoked responses in spinal neurons therefore involves a temporal summation of d‐APV sensitive prolonged postsynaptic depolarizations.
Re‐expression of Nerve Growth Factor Receptor after Axonal Injury Recapitulates a Developmental Event in Motor Neurons: Differential Regulation when Regeneration is Allowed or Prevented
Authors: Wood S. J. , Pritchard J. , Sofroniew M. V. 
Published: April 2006

AbstractMotor neurons in the brainstem and spinal cord transiently express nerve growth factor receptors (NGFr) during development, but not in normal adult animals. In this study, NGFr was immunohistochemically identified in hypoglossal motor neurons after different types of peripheral axonal injury in adult rats. NGFr is re‐expressed in motor neurons 7 days after a nerve crush injury, and has disappeared again by 28 days. These times correspond, respectively, to the active phase of regeneration, and a time by which regeneration has largely been completed, as determined by electrical activation of tongue muscle twitch. In contrast, 7 days after nerve transection and ligation of the proximal stump to prevent regeneration, there is no re‐expression of NGFr, but 28 days after such treatment NGFr is present in a few neurons. By this time, neuroma formation has begun proximal to the end of the cut and ligated nerve. Together, these findings suggest that motor neurons transiently re‐express NGFr during regeneration and not in response to axonal transection per se. The signal triggering re‐expression thus seems more likely to be the introduction of a message from the site of injury, rather than the loss of a target‐derived message. Although the function of NGFr in developing and regenerating motor neurons is not known, its expression appears to be associated with periods of axonal growth and maturation.
Striatal NPY‐Containing Neurons Receive GABAergic Afferents and may also Contain GABA: An Electron Microscopic Study in the Rat
Authors: Vuillet J. , Goff L. Kerkerian‐Le , Kachidian P. , Dusticier G. , Bosler O. , Nieoullon A. 
Published: April 2006

AbstractDual labelling methods were applied to localize simultaneously neuropeptide Y (NPY) and glutamate decarboxylase (GAD) immunoreactivities on ultrathin sections of the rat caudate‐putamen (CP). By means of a double peroxidase‐anti‐peroxidase technique, using 3,3′‐diaminobenzidine and benzidine dihydrochloride as chromogens in animals with no colchicine pretreatment, GAD immunoreactivity was found to be present in terminals only whereas NPY immunoreactivity was detected in neurons displaying the features of aspiny type cells and processes. With this approach, we observed numerous synaptic associations of the symmetrical type between GAD‐immunoreactive (‐Ir) axonal boutons and NPY‐Ir cell bodies and dendrites. By combining immunoperoxidase and radioimmunocytochemical labelling in animals pretreated with colchicine, NPY was again detected in a single population of aspiny type neurons whereas GAD immunoreactivity was observed in neurons which could be classified as aspiny and spiny on the basis of their ultrastructural characteristics. All the cells of the aspiny type displaying clear‐cut NPY immunoreactivity were also found to be GAD‐positive. Some other neurons of both the aspiny and the spiny type were found to be immunoreactive to GAD alone. GAD/NPY dually labelled terminals were also observed and some axo‐axonic appositions between GAD‐ and NPY‐Ir terminals were also detected. All in all, these data show that NPY aspiny type neurons of the rat CP receive GABAergic afferents and provide morphological support for two hypotheses: that NPY is co‐localized with GABA in some cell bodies, dendrites and axons, and that presynaptic interactions may occur between NPY and GABAergic neuronal systems.
The Maturation of the Superior Collicular Map of Auditory Space in the Guinea Pig is Disrupted by Developmental Visual Deprivation
Authors: Withington‐Wray D. J. , Binns K. E. , Keating M. J. 
Published: April 2006

AbstractIn the normal guinea pig a map of auditory space appears, in the deeper layers of the superior colliculus, at 32 days after birth (DAB). The animal is unable to construct this collicular map of auditory space in the absence of developmental visual experience. Auditory receptive fields of animals dark‐reared from birth are typically large, occupying most of the contralateral hemifield. There is no topographic relationship between the collicular location of the recording electrode and the spatial position from which auditory stimuli elicit a maximal response. The fields of dark‐reared animals resemble, in their tuning parameters, the spatially undifferentiated fields typical of young postnatal normal guinea pigs. To investigate the time‐course during which visual experience is required for map emergence, animals received normal visual experience until either 18 or 26 DAB and were then dark‐reared until the terminal mapping experiment. Maps developed in neither group. Animals provided with a normal visual environment until 30 DAB, and then placed in the dark did, however, construct topographically organized spatial maps with discrete spatial receptive fields. Maps also failed to emerge in animals receiving normal visual experience both before and after a 4‐day period of visual deprivation between 26 and 30 DAB. We conclude that this 4‐day period, or part of it, constitutes a ‘crucial’ period during which visual experience is required for the normal elaboration of the collicular map of auditory space.
A Collection of cDNA Clones with Specific Expression Patterns in Mouse Brain
Authors: Kato Kikuya 
Published: April 2006

AbstractA total of 950 cDNA clones were randomly selected from mouse cerebellar cDNA libraries, and of these, about 130 clones were found to correspond to mRNAs which were expressed unequally between the cerebellum and other parts of mouse brain. Their distribution patterns in adult mouse brain were analysed by in situ hybridization, and eight clones were found restricted to specific regions of the brain, including four clones specific to cerebellar granule cells and one clone specific to Purkinje cells. Another 27 clones were preferentially expressed in a diverse, but distinctive subpopulation of brain cells. Among them seven clones were especially abundant in specific nuclei, and three in specific fibre bundles. These clones will be useful in defining new subpopulations of brain cells characterized by different gene expression.
Insulin and Neuroparsin Promote Neurite Outgrowth in Cultured Locust CNS
Authors: Vanhems Elisabeth , Delbos Marline , Girardie Josiane 
Published: April 2006

AbstractOrganotypic cultures of locust embryo central nervous system (CNS) were used to study the influence of hormonal factors on neurite outgrowth. Explants from the third thoracic ganglion (embyronic day 9) were grown in a serum‐free medium and exposed to insulin, neuroparsin, a recently characterized insect neurohormone, somatostatin and two insect hormones: 20‐hydroxyecdysone and juvenile hormone. These hormonal factors were tested either alone or in several combinations. In our culture system both insulin and neuroparsin promoted extensive neurite outgrowth. Their effects were quantitatively similar. Somatostatin had no effect on neurite formation, but was a growth factor for glial cells. 20‐hydroxyecdysone was a required factor for glial cell and neurite survival. Juvenile hormone did not have any observable effects in this culture system. When insulin was added in combination with 20‐hydroxyecdysone the stimulation of neurite outgrowth exceeded that seen when insulin was added alone. A similar enhancement was observed with the combination of neuroparsin and 20‐hydroxyecdysone. We conclude that in locusts: (i) insulin can be implicated as a neurotrophic factor as in vertebrates; and (ii) neuroparsin, a locust neurohormone, can also be characterized as a neurotrophic factor for the locust. Moreover, both neurohormones interact synergistically with the steroid hormone 20‐hydroxyecdysone to enhance neurite growth.
Effect of Glutamate and lonomycin on the Release of Arachidonic Acid, Prostaglandins and HETEs from Cultured Neurons and Astrocytes
Authors: Oomagari Kiyoshi , Buisson Bruno , Dumuis Aline , Bockaert Joël , Pin Jean‐Philippe 
Published: April 2006

AbstractThe release of arachidonic acid (ArA) metabolites from mouse neurons and astrocytes in primary culture has been studied in response to ionomycin or glutamate stimulation. Cells were preincubated with [3H] ArA for 24 h and the radioactivity released was examined by HPLC. In striatal, cortical and hippocampal neurons, glutamate and ionomycin strongly stimulated the release of ArA, but neither prostaglandins (PGs) nor hydroxyeicosatetraenoic acids (HETEs) could be detected. If they were released, these latter compounds represented < 0.02% of the amount of ArA. In contrast, in astrocyte cultures, ionomycin (but not glutamate) strongly stimulated the release of PGs and HETEs as well as ArA. Reversed‐ and straight‐phase HPLC analysis revealed the presence of PGD2, PGE2, PGF2α, 12‐hydroxyheptadeca‐5, 8,10‐trienoic acid (HHT) and HETEs (15‐HETE, 11‐HETE and 5‐HETE). Indomethacin inhibited the release of PGs and HHT, but also that of 11‐ and 15‐HETE, indicating that these two HETEs may be produced through the cyclooxygenase pathway. Metabolism of [3H]ArA was also examined in cellular homogenates. Although > 50% of the [3H]ArA was metabolized to PGF2α, PGE2, PGD2, HHT, 15‐ and 11‐HETE in cultured astrocyte homogenates, no [3H]ArA metabolism could be detected in cultured striatal neuron homogenates. Moreover, neuronal homogenates did not inhibit the metabolism of [3H]ArA observed in either astrocyte or platelet homogenates. These results indicate that central neurons in primary culture possess very low lipoxygenase and cyclooxygenase activities. They emphasize the need to identify the cellular source of ArA metabolites in the brain, particularly when considering the multiple new messenger roles proposed for these molecules, such as that of retrograde messengers involved in synaptic plasticity phenomena.
Developmentally Regulated Expression of HDNF/NT‐3 mRNA in Rat Spinal Cord Motoneurons and Expression of BDNF mRNA in Embryonic Dorsal Root Ganglion
Authors: Ernfors Patrik , Persson Hakan 
Published: April 2006

AbstractNorthern blot analysis was used to demonstrate high levels of hippocampus‐derived neurotrophic factor/ neurotrophin‐3 (HDNF/NT‐3) mRNA in the embryonic day (E) 13–14 and 15–16 spinal cord. The level decreased at E18–19 and remained the same until postnatal day (P) 1, after which it decreased further to a level below the detection limit in the adult. In situ hybridization revealed that the NT‐3 mRNA detected in the developing spinal cord was derived from motoneurons and the decrease seen at E18–19 was caused by a reduction in the number of motoneurons expressing NT‐3 mRNA. The distribution of NT‐3 mRNA‐expressing cells in the E15 spinal cord was very similar to the distribution of cells expressing choline acetyltransferase or nerve growth factor receptor (NGFR) mRNA. Moreover, a striking similarity between the developmentally regulated expression of NT‐3 and NGFR mRNA was noted in spinal cord motoneurons. A subpopulation of all neurons in the dorsal root ganglia expressed brain‐derived neurotrophic factor (BDNF) mRNA from E13, the earliest time examined, to adulthood. These results are consistent with a trophic role of NT‐3 for proprioceptive sensory neurons innervating the ventral horn, and imply a local action of BDNF for developing sensory neurons within the dorsal root ganglia.
L‐Homocysteate Preferentially Activates N‐methyl‐D‐aspartate Receptors to CA1 Rat Hippocampal Neurons
Authors: Provini L. , Ito S. , Ben Ari Y. , Cherubini E. 
Published: April 2006

AbstractIntracellular recordings and current and single‐electrode voltage‐clamp techniques were used to study the membrane responses of CA1 pyramidal neurons to bath application of L‐homocysteic acid (L‐HC) in the rat hippocampal slice preparation. In control artificial cerebrospinal fluid (ACSF), L‐HC (25 ‐ 250 μM) depolarized the membrane and induced a burst‐like firing pattern. Both the membrane depolarization and the burst firing were blocked by the N‐methyl‐D‐aspartic acid (NMDA) receptor antagonists D‐(‐)‐2‐amino‐5‐phosphonovaleric acid (AP‐5, 50 μM), D‐(‐)‐2‐amino‐7‐phosphonoheptanoic acid (AP‐7, 50 μM) and (±)‐3‐(2‐carboxy‐pipera‐zin‐4‐yl)‐propyl‐1‐phosphonic acid (CPP, 20 μM). In ACSF containing tetrodotoxin (1 μM), L‐HC (100–300 μM) induced at resting membrane potential a depolarization which was associated with a small increase in input conductance. These effects were unaffected by 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX, 10–20 μM) but were fully blocked by AP‐5, AP‐7 (50 μM) and CPP (10–20 μM). In voltage‐clamp experiments, L‐HC induced slow inward currents which were voltage‐dependent between ‐ 70 and ‐ 30 mV and reversed polarity near 0 mV. The L‐HC‐induced inward current was unaffected by CNQX (10–20 μM) but was strongly reduced by AP‐5 or AP‐7 (50 μM). The L‐HC‐induced inward current was temperature‐dependent. Between ‐60 and ‐70 mV, its amplitude increased by 320% when the temperature was lowered from 33 to 22°C. The L‐HC‐induced current was also potentiated by the specific L‐HC uptake blocker β‐p‐chlorophenylglutamate (Chlorpheg, 0.5–2 mM). These data suggest that L‐HC preferentially activates NMDA receptors in CA1 hippocampal neurons.
Lesions of the Cerebral Cortex and Caudate‐Putamen Enhance GABA Function in the Rat Superior Colliculus
Authors: Kilpatrick I. C. , Neal J. W. , Pearson R. C. A. , Powell T. P. S. 
Published: April 2006

AbstractUnilateral lesions of the rat frontal cortex were made either alone or in combination with the caudate‐putamen in order to examine (a) their morphological influence on the substantia nigra and (b) their neurochemical influence on GABA function in the superior colliculus. One to two months following the combined lesion, neuronal somata in the ipsilateral pars reticulata of the substantia nigra were clearly hypertrophied (+ 30%). Morphological changes in the substantia nigra were not evident contralateraly or in animals bearing only cortical lesions. One to two months following cortex‐only lesions, no significant alterations in tectal GABA concentration were observed. However, the combined lesion induced elevations of GABA within both the medial and lateral sectors of the intermediate and deep layers of the superior colliculus. This effect was restricted to the ipsilateral side and was most pronounced in lateral sectors. The vast majority of GABA released from superfused control tectal slices by a depolarizing stimulus (35 mM KCI) was calcium‐dependent. Such evoked GABA release from ipsilateral tectal slices was significantly reduced (‐25%) by unilateral lesions of the substantia nigra, a structure that is known to provide GABA‐containing inputs to the tectum. In contrast, cortical lesions alone significantly enhanced the evoked tectal GABA release (+ 66%), although their influence was again confined to the ipsilateral side. Combined lesions of the cerebral cortex and caudate‐putamen significantly enhanced the evoked GABA release from tectal slices in both hemispheres but the changes were most marked ipsilaterally (+ 147%). It is suggested that the hypertrophy of GABA‐containing nigrotectal somata seen after removal of corticostriatal, corticotectal and in particular GABA‐containing striatonigral fibres may reflect concomitant increases in GABA synthesis within and/or sprouting of nigrotectal terminals.
The Effect of Calcium Channel Antagonists on Spontaneous and Evoked Epileptiform Activity in the Rat Neocortex In Vitro
Authors: Boulton Caroline L. , O'Shaughnessy Celestine T. 
Published: April 2006

AbstractCalcium influx through voltage‐activated calcium channels may play a crucial role in the propagation and maintenance of seizure activity. We have examined the contribution of various types of calcium currents to epileptogenesis by studying the effects of various calcium channel blockers on epileptiform activity. N‐methyl‐d‐aspartate receptor‐mediated epileptiform activity was induced by removal of magnesium ions superfusing the cortex, or by low‐frequency stimulation of the underlying white matter. CoCl2, CdCl2 and ω‐conotoxin, acting at the N‐ and L‐type calcium channels, significantly reduced epileptiform activity. L‐channel antagonists nifedipine and verapamil, and the agonist BAY K 8644, increased spontaneous bursting in cortical wedges, but had no effect upon evoked activity. The T‐channel blocker NiCI2 had variable effects on epileptiform activity, whereas phenytoin consistently reduced such activity. These results suggest that calcium influx underlying epileptiform activity in the rat neocortex may occur at least partially via the activation of the N‐type calcium channel. However, contributions from other calcium channel types cannot be excluded.
Nerve Growth Factor Receptor‐immunoreactive Fibres Innervate the Reticular Thalamic Nucleus: Modulation by Nerve Growth Factor Treatment in Neonate, Adult and Aged Rats
Authors: Fusco M. , Bentivoglio M. , Vantini G. , Guidolin D. , Polato P. , Leon A. 
Published: April 2006

AbstractTerminal arborizations expressing nerve growth factor receptor (NGF‐R) have been detected with immunohistochemistry in the reticular thalamic nucleus of neonate, adult and aged rats. Intracerebroventricular administration of nerve growth factor (NGF) resulted in a dramatic increase in NGF‐R immunoreactivity throughout the lifespan. This effect was paralleled by a concomitant increase in NGF‐R immunopositivity in the neurons of the basal forebrain, which was here demonstrated also in aged animals, thus indicating that the NGF‐R immunoreactivity within the reticular thalamic nucleus derives in all likelihood from cholinergic neuronal cell bodies of the basal forebrain. Our results demonstrate a prominent ability of NGF to up‐regulate its receptors within fibres innervating the reticular thalamic nucleus, and show that this up‐regulation of NGF‐R is maintained throughout the lifetime. Altogether this indicates that the reticular thalamic nucleus may represent a new, important site of action of endogenous NGF or NGF‐like molecules within the brain. In view of the crucial role played by the reticular thalamic nucleus in gating thalamocortical information, the autoregulation of NGF‐R in this structure may have important concomitants in both physiological and pathological conditions.