Biomedical subjects

J Caboche

Publications and source records attributed to J Caboche.

23 records · Page 2Linked to original sources

PubMed1991

Comparative development of D1-dopamine and mu opiate receptors in normal and in 6-hydroxydopamine-lesioned neonatal rat striatum: dopaminergic fibers regulate mu but not D1 receptor distribution.

The postnatal development of D1 dopaminergic receptors (D1 receptors) was investigated in the rat striatum in relation to distribution of mu opiate receptor patches and islandic tyrosine hydroxylase (TH)-immunoreactive fibers. The possible influence of dopaminergic (DA) fibers originating from the substantia nigra on the postnatal distribution of striatal D1 and mu receptors was also examined by producing an early 6-hydroxydopamine (6-OHDA) lesion of DA fibers. D1 and mu receptors were labeled with selective ligands: [3H]SCH 23390 and [3H]DAGO, respectively. During the first postnatal week, control rats showed patches of dense D1 binding sites in the entire rostro-caudal extension of the striatum. The localization of D1 receptor patches corresponded to striosomes identified by TH-immunoreactive islands. The striatal distribution of mu receptors was relatively homogeneous at postnatal day 0 (P0) but was clearly patchy at P3-P4. During the second postnatal week the striosomal pattern of D1 binding sites disappeared along a dorso-ventral gradient whereas mu binding sites remained distributed in patches. Densitometric measurements showed that there was a parallel increase of D1 binding sites in both striosomes and the surrounding matrix from P0 to P4. The disappearance of D1 receptor patches observed in the dorsal striatum at P9 was due to a faster increase of D1 binding sites in the matrix than in striosomes between P4 and P9 whereas a significant difference was still observed between these two compartments in the ventral striatum of P9 rats. During the third postnatal week, the density of D1 binding sites still increased but became progressively uniform in the whole striatum. The intrastriatal injection of 6-OHDA in 2-day-old rats produced a local disappearance of TH-immunoreactive fibers in the striatum and a distal degeneration of TH-immunoreactive cell bodies in the substantia nigra. However an early lesion of striatal DA fibers did not modify the pattern of development or the density of D1 binding sites during the postnatal period examined (1 and 3 weeks after the lesion). The distribution of mu receptors was unchanged 1 week after the lesion but showed a clear disorganization 3 weeks after the lesion. We discuss the differential influence of DA fibers on the distribution of D1 and mu receptors in the rat striatum and the possible role of DA in the regulation of the expression of mu receptors.

Animals↗

PubMed1991

Parallel decrease of glutamic acid decarboxylase and preproenkephalin mRNA in the rat striatum following chronic treatment with a dopaminergic D1 antagonist and D2 agonist.

The levels of mRNA encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE) were measured by Northern blot analysis, in the dorsal and the ventral part of the striatum, following long-term treatments with drugs acting selectively on D1 or D2 dopaminergic receptors. Chronic injection of the selective D1 antagonist SCH 23390 elicited a significant decrease in level of both GAD and PPE mRNA (-30%) in the dorsal striatum, whereas no significant change was observed in the ventral striatum. Chronic administration of both SCH 23390 and RU 24926, a D2 agonist, decreased the GAD and PPE mRNA levels in the dorsal (-38 and -57%, respectively) as well as in the ventral (-70 and -60%, respectively) striatum. In the ventral striatum the marked reduction of GAD mRNA levels was paralleled by a significant decrease of Vmax values of GAD enzymatic activity (-41%). These results suggest that the decrease in content of both GAD and PPE mRNA, promoted by the chronic blockade of D1 receptors, is mainly due to the action of dopamine acting on unaffected D2 receptors. Indeed, this decrease is further amplified when the D2 agonist and the D1 antagonist are administered together. Our results substantiate further the molecular mechanisms by which dopamine acts on different populations of GABAergic and enkephalinergic neurons in the two striatal regions examined.

Animals↗

PubMed1989

Postnatal evolution of the gamma-aminobutyric acid/benzodiazepine receptor complex in a model of inherited epilepsy: the quaking mouse.

Binding assays of [3H]muscimol and [3H]-flunitrazepam have been performed on brain homogenates of brainstem, cerebellum, and forebrain of genetically epileptic quaking (qk) mutant mice 20, 40, 70, and 90 days old and their corresponding controls of the same strain (C57BL/6J). The endogenous gamma-aminobutyric acid (GABA) content has been determined in various brain regions of 70-day-old qk and control mice. Finally, the behavioral effects of diazepam, of the mixed GABAA/GABAB receptor agonist progabide, and of the selective GABAB receptor agonist baclofen have been assessed in adult qk mutants. Our results strongly suggest a lack of involvement of GABAergic neurotransmission in the inherited epilepsy of the qk mutant mouse.

Aging↗

PubMed1983

Alterations of noradrenaline and serotonin uptake and metabolism in chronic cobalt-induced epilepsy in the rat.

The high affinity uptake of noradrenaline and serotonin, and the concentrations of these monoamines and their metabolites, have been measured in the perifocal cortical area at various stages of the evolution of cobalt-induced epilepsy in the rat. Noradrenaline uptake was maximally reduced at days 8-10 after cortical cobalt application, a time corresponding to the onset of epileptic discharges; it remained diminished during the spiking activity period of the focus (days 14-20) and was back to normal values at day 40, at which time the epileptic syndrome had disappeared. Serotonin uptake was also diminished at days 8-10 but to a lesser extent than was noradrenaline uptake. In the homotopic cerebral cortex contralateral to cobalt application, noradrenaline uptake was reduced at day 10 only and to a lesser extent than in the perifocal area, whereas serotonin uptake was unaffected. Kinetic analysis of the cobalt-induced monoamine uptake alterations at day 10 revealed a diminution of the maximal velocity with no change in the Km. Noradrenaline and dihydroxyphenylethyleneglycol concentrations in the perifocal area were also maximally reduced at days 8-10 but were unaffected at day 2 and day 40 post cobalt application. A reduction of serotonin levels in the perifocal area was observed only at days 8-10 while 5-hydroxyindoleacetic acid remained unaffected throughout the time period studied. The levels of these monoamines and their metabolites were unchanged in the homotopic contralateral cortex 2-40 days after cobalt application. These results indicate that cortical cobalt application induces alterations of the biochemical indices of the density of noradrenaline-containing terminals that closely parallel the evolution of the epileptic syndrome. These data further emphasize the important role of the cortical noradrenergic system in cobalt-induced epilepsy.

Animals↗

PubMedDate not supplied

Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain: a molecular substrate for learning and memory?

The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway is an evolutionarily conserved signaling cascade involved in a plethora of physiological responses, including cell proliferation, survival, differentiation, and, in neuronal cells, synaptic plasticity. Increasing evidence now implicates this pathway in cognitive functions, such as learning and memory formation, and also in behavioral responses to addictive drugs. Although multiple intracellular substrates can be activated by ERKs, nuclear targeting of transcription factors, and thereby control of gene expression, seems to be a major event in ERK-induced neuronal adaptation. By controlling a prime burst of gene expression, ERK signaling could be critically involved in molecular adaptations that are necessary for long-term behavioral changes. Reviewed here are data providing evidence for a role of ERKs in long-term behavioral alterations, and the authors discuss molecular mechanisms that could underlie this role.

Animals↗