Neuroscience
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Angiotensin II-(3-8)-hexapeptide, at the dose of 1 nmol given intracerebroventricularly, only slightly less than angiotensin II (the same dose and route) stimulated exploratory locomotor behaviour in an open field and electromagnetic motimeter. Both peptides considerably enhanced stereotyped behaviour produced by apomorphine and amphetamine. ⋯ The results indicate that the effectiveness of equimolar doses of angiotensin II-(3-8)-hexapeptide and angiotensin II in improving processes related to learning and memory in rats is almost identical and thus must be independent of specific angiotensin receptors in brain to which the hexapeptide binds with about 1000 times lower affinity than angiotensin II. The stimulation of stereotypy, a dopamine-controlled behaviour, by the peptides points to the possibility of dopaminergic mediation of their psychotropic effects.
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Ablation of capsaicin-sensitive afferent neurons enhances experimentally induced ulceration in the rat gastric mucosa, which suggests that these neurons are involved in gastric mucosal protection. To provide direct evidence for such a function it was investigated whether stimulation of afferent nerve endings by the intragastric administration of capsaicin could counteract the ulcerogenic effect of 25% ethanol. Capsaicin (3.2-640 microM), administered together with ethanol, inhibited the development of haemorrhagic lesions in a concentration-dependent fashion but did not alter the ethanol-induced fall in the gastric potential difference. ⋯ The protective effect of intragastric capsaicin was not altered following acute subdiaphragmatic vagotomy, acute removal of the coeliac-superior mesenteric ganglion complex, acute bilateral ligation of the adrenal glands, or pretreatment of the rats with atropine or guanethidine. These findings indicate that stimulation of afferent neurons by intragastric capsaicin affords protection of the rat gastric mucosa against ethanol-induced damage. As the autonomic nervous system is not involved gastroprotection appears to represent a local effector function of sensory nerve endings in the stomach.
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This paper examines the topography of neuronal degeneration in the central nervous system of the dystonia musculorum (dt) mutant mouse, revealed by selective silver impregnation, specific histochemical staining and electron microscopy. Neuronal lesions have been observed exclusively in the spinal cord, the medulla and the anterior lobe of the vermis. In the spinal cord, axonal degeneration was maximal among large and medium-sized primary sensory fibers, whereas thin caliber primary afferents were unaffected, with the exception of those containing acid phosphatase activity. ⋯ This study also suggests a simple pathophysiological mechanism for the onset and the progression of the degeneration: dystonic gene action would affect perinatally specific classes of sensory receptors, producing the degeneration of the nerve terminals and, progressively, the cell death of the sensory ganglion cells at their origin. This retrograde death, which results in the massive and early deafferentation of spinocerebellar neurons, would provoke, trans-neuronally, the impairment of these second order sensory neurons and the progressive degeneration of the spinocerebellar system. The close resemblance of the neuropathology of the mutant mouse to Friedreich's ataxia (the commonest form of human degenerative ataxic disorders) allows one to suppose that the dystonic mouse may be an optimal animal model for studying the genetic basis and the pathophysiological mechanisms of this form of human ataxia.
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Specific antibodies raised in rabbits against 3-hydroxyanthranilic acid oxygenase (EC 1.13.11.6) and quinolinic acid phosphoribosyltransferase (EC 1.13.11.6) and quinolinic acid phosphoribosyltransferase (EC 2.4.2.19) were used in immunohistochemical studies to map the cellular localization of the quinolinic acid metabolizing enzymes in the adult male rat brain. 3-Hydroxyanthranilic acid oxygenase immunoreactivity was found to be present in glial cells of presumed astroglial identity, as judged by co-localization with glial fibrillary acidic protein. 3-Hydroxyanthranilic acid oxygenase-immunoreactive glial cells were present in all brain regions and within major fiber tracts. The density of 3-hydroxyanthranilic acid oxygenase-immunoreactive glial cells as well as the intensity of staining of these cells differed among brain regions. In general, telencephalic acid diencephalic areas harbored a larger number of 3-hydroxyanthranilic acid oxygenase-positive cells than did mesencephalic regions. ⋯ In addition to staining of glial cells, neuronal cell bodies containing 3-hydroxyanthranilic acid oxygenase immunoreactivity were detected in the main and in the accessory olfactory bulb, as well as in the ventromedial nucleus of the hypothalamus. Quinolinic acid phosphoribosyltransferase immunoreactivity was observed within glial cells and in association with neuronal cell bodies. Some, but not all, quinolinic acid phosphoribosyltransferase positive glial cells contained glial fibrillary acidic protein (Köhl
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Trimethyltin is a neurotoxicant which produces a distinct pattern of neuronal cell death following peripheral administration of a single dose (8 mg/kg, i.p.) in rats. The cupric-silver degeneration stain was used to produce an atlas documenting the distribution and time course of trimethyltin-induced neuronal damage in adult, male Long-Evans rats. Animals were examined at survival times of 1, 2, 3, 4, 5, 7, 10 and 18 days after intoxication. ⋯ Protein-O-carboxyl methyltransferase immunoreactivity was altered in neuronal populations damaged by trimethyltin, but did not appear to be either as sensitive or selective an assay of neuronal damage as the silver stain, especially at short survival times. Glial fibrillary acidic proteins were dramatically elevated 21 days after trimethyltin intoxication, particularly in areas of extensive damage. These studies revealed advantages and problems encountered in the use of each technique in assessing neurotoxic effects, forming a basis for discussion of the relative merits of using a battery of specific molecular probes for neurotoxicity evaluations.