The acute effects of dopamine D2 antagonists and agonists on the expression of c-jun, zif-268, ETR101 and c-fos in the rat striatum were studied. A single injection IP of haloperidol (2 mg/kg) or sulpiride (100 mg/kg) produced a rapid and transient increase in c-jun, zif-268 and c-fos mRNA. ETR101 was not activated. These inductions were dose dependent and were specifically blocked by pretreatment with a D2 agonist (1 mg/kg quinelorane). Quinelorane alone had no effect. Thus, dopamine D2 receptors inhibit the expression of a particular set of immediate early genes in the striatum.

Animals↗

PubMedDate not supplied

[Multiple sclerosis: review of main experimental data and pathogenic hypotheses].

The pathogenesis of multiple sclerosis (MS) is considered from three different viewpoints: genetic, viral and immunological. A genetic predisposition intervenes, as testified by the familial forms of MS and by the frequency of HLA A3B7 and DR2 groups in MS patients. The hypothesis of an inherited enzyme deficiency in oligodendrocytes is discussed. Many viruses are known to induce demyelination in animals, and the intrathecal production of antibodies to measles virus as well as the in vitro discovery of DNA transcripts of this virus in patients are suggestive of a viral factor. Experimental allergic encephalomyelitis (EAE) and chronic EAE have made it possible to study the immune and other mechanisms which might be involved in MS. While the myelin basic protein and the M2 antigen appear to be the first antigen targets, the demyelinating agents in this model are antibodies to galactocerebroside. The factors responsible for demyelination in MS have not yet been elucidated, but the antibodies present in the cerebrospinal fluid do not seem to be demyelinating in vitro. Descriptions of the cells which constitute the lesions and of the antigen markers they express suggest that endothelial cells and astrocytes (possibly presenting antigens to lymphocytes) might play a part in the genesis of the lesions. Experiments concerning the modulation and suppression of EAE allow new therapeutic approaches to be envisaged.

Animals↗

PubMedDate not supplied

Amino-acid sequence determination of a hydrophobic region of bovine rhodopsin.

The 50 amino acid residues sequence of a hydrophobic region of bovine rhodopsin, a membrane protein of retinal rod photoreceptors of molecular weight 39,000 was determined. This primary structure determination was performed on the S5 fragment (about 12,000 molecular weight) obtained from 2-(2 nitrophenylsulfenyl)-3-methyl-3'bromo-indolenine cleavage of the protein. Automatic Edman degradation used in liquid phase was performed in presence of N-cetyl-N,N,N-trimethyl-ammoniumbromide, a cationic detergent incorporated in the proteic film. S5 is a C-terminal rhodopsin fragment and contains the phosphorylation sites. The covalent structure determined overlaps with the sequence of an already known fragment [1]; thus 25 per cent of the rhodopsin primary structure is now elucidated. Our results are in agreement with and chiefly refine the topological model for rhodopsin which correlates its membrane location and its functional sites.

Amino Acid Sequence↗

PubMedDate not supplied

Localization of S100 protein in the rat cerebellum: an immunoelectron microscope study.

Immunoelectron microscopy has shown that, in adult rat cerebellum, S100 protein is localized exclusively in the astroyctes of both the cortex and the white matter. The labelling pattern was unaffected by the inclusion of glutaraldehyde in the primary paraformaldehyde fixative. The immunoperoxidase reaction product is observed over both the perikaryal cytoplasm of astrocytes and their processes. S100 proteins was not found in neuronal structures nor in oligodendrocytes.

Animals↗

PubMedDate not supplied

Effects of thyroid state and undernutrition on S100 protein and astroglia development in rat cerebellum.

The developmental pattern of S100 protein, a specific marker of astroglia, was studied by radioimmunoassay in the cerebellum of thyroid-deficient, thyroxine-treated and undernourished rats during development. In the control animals, the S100 protein content of the cerebellum increased maximally after the 3rd postnatal week, i.e., after cell multiplication had stopped and when the cerebellum had acquired more than 70% of its adult weight and protein content. This developmental pattern of S100 protein reflected essentially the maturation of astroglia. In the thyroxine-treated rats the total amount and the concentration of S100 protein were higher than in controls during the first 3 weeks of postnatal life and returned to normal values thereafter. In the thyroid-deficient rats both the amount and concentration were lower than in controls throughout development. In the undernourished animals the amount of S100 protein per organ was also lower than in controls during the whole experimental period studied; the S100 protein concentration was higher during the first 2 postnatal weeks and became lower thereafter. These results are discussed taking into consideration previous histological and ultrastructural observations on the effects of altered thyroid state and undernutrition on the formation and maturation of cerebellar astrocytes.

Animals↗

PubMedDate not supplied

[Induction by neuroleptics of certain genes in the central nervous system].

Prolonged administration of neuroleptic drugs increases the density of dopamine D2 receptors in several brain regions. We have recently shown that such treatment also raises dopamine D2 receptor mRNA levels in the striatum. To elucidate some of the initial events which lead to this upregulation, we studied the acute effects of dopamine D2 agonists and antagonists on the expression of c-jun and c-fos. A single injection I.P. of haloperidol (2 mg/kg) produced a rapid and transient increase in c-jun and c-fos mRNA in the rat striatum. This induction was specifically blocked by a D2 agonist (1 mg/kg quinelorane). In contrast, by itself quinelorane was without effect. These results show that dopamine D2 receptors inhibit the expression of a set of immediate early genes in the striatum, and these may be involved in the up-regulation of D2 mRNA upon prolonged neuroleptic treatment.

Animals↗