Publications du Neurocentre Magendie

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IF du Neurocentre

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The anatomical and functional characteristics of dopamine neuron-rich grafts implanted into rat pups were compared with those of identical grafts implanted into adult hosts. The host nigrostriatal dopaminergic pathway was unilaterally destroyed by an intrahypothalamic injection of 6-hydroxydopamine. This was followed five days later by the implantation of a cellular suspension obtained from rat embryonic mesencephali. Identical operations were carried out on adult and infant (PD3) rats. The survival rate of implanted tyrosine hydroxylase-positive cells was lower in the neonates. On the other hand, in the neonate hosts, surviving immunoreactive cells migrated extensively throughout the host striatum coursing preferentially below the corpus callosum and towards the subependymal zone. The structural integrity of the host parenchyma was well maintained after the neonatal implantation, in contrast to that observed in the adults. Despite a difference in the cell survival rate, there was no major difference in reinnervation density between the two types of host. The functional capacities of the implants were evaluated by measuring the rotational responses of the animals to dopaminergic agonists. The implants compensated the lesion-induced contralateral rotational response to the mixed agonist apomorphine and the D1 agonist SCH-38393 in both neonates and adults. However, the response to the D2 agonist LY-171555 was not significantly attenuated by the implant. The ipsilateral rotational response to amphetamine observed in the lesioned animals was also compensated and even reversed by the graft. It is concluded that with respect to rotational behavior, similar functional benefits were observed following adult stage or neonatal implantation, despite differences in their anatomical development.

The ascending dopaminergic system of adult or 3-day-old rats has been unilaterally lesioned by the intraparenchymal injection of 6-hydroxydopamine aimed at the medial forebrain bundle at the level of the lateral hypothalamus. Nigral dopaminergic neurons disappeared following the lesion on the lesioned side in both experimental groups while the depletion of the ventral tegmental area was less extensive, especially following the neonatal lesion. Striatal regions were markedly depleted of their dopaminergic innervation, although the magnitude of the depletion was slightly higher following the adult stage lesion as judged on the basis of biochemical measurements (99% vs. 96%). Amphetamine (5 mg/kg) evoked an identical ipsilateral rotational response in both experimental groups. Moreover, this rotational response was blocked both by the specific D1 receptor blocker SCH-23390 (0.1 mg/kg) and the specific D2 receptor antagonist raclopride (2 mg/kg). Likewise, contralateral rotational responses to the directly acting D1 and D2 dopamine receptor agonists SKF-38393 (2.5 mg/kg) and LY-171555 (0.15 mg/kg) were similar in both experimental groups, both qualitatively and quantitatively. These results confirm conclusions obtained in earlier works, and indicate that reported differences in behavioral deficits between animals lesioned as neonates or adults are not related to differing modifications of striatal DA receptor sensitivities.

09/1990 | Neurobiol Aging   IF 4.5
A comparison of the working memory performances of young and aged mice combined
Lebrun C, Durkin TP, Marighetto A, Jaffard R

The spatial working memory performances of young (2 months) and aged (24-26

The ascending mesotelencephalic dopaminergic systems of rat pups of 3 days of age were bilaterally lesioned using 6-hydroxydopamine injected at the level of the lateral hypothalamus. A sub-group of lesioned pups received, 5 days after the lesion, a dopamine neuron-rich cell suspension graft implanted bilaterally into the striatum and nucleus accumbens. Behavioral tests were conducted 6 months later. The lesion induced an increase in the locomotor activation induced by D-Ala2-Met5-enkephalinamide injected into the nucleus accumbens (2.5 micrograms/side) as compared to the activation observed in control animals. Locomotor activation by systemic apomorphine (0.1 mg/kg s.c.) was also increased while that induced by amphetamine (1.5 mg/kg i.p.) was abolished. The presence of DA neuron implants reversed each of these post-lesion modifications.

The aim of the present experiments was to test whether adrenal chromaffin cells implanted into the striatum of rats could exert a functional effect through a release of catecholamines. A cell suspension obtained from bovine adrenal medulla was implanted unilaterally into the striatum. The striatal dopaminergic input was extensively destroyed beforehand to preclude the possibility of reinnervation of the striatum by endogenous dopaminergic neurons. The functional influence of the implant was tested through the measurement of drug-induced rotation, while catecholamine release was measured subsequently in the same animals by in vivo electrochemistry. Transplant survival, as shown by the immunohistochemical analysis performed at the end of the in vivo experiments, was highly variable. Surviving chromaffin cells maintained their endocrine morphology and no reinnervation of the host striatum could be detected. Rotation of the animals evoked by apomorphine (0.1 mg/kg, sc) or amphetamine (5.0 mg/kg, ip) following the lesion was left uninfluenced following transplantation, even when a large transplant was recovered. On the other hand, nicotine (0.5 mg/kg, sc) evoked a strong contraversive rotational response in the transplant-bearing animals. This response could not be ascribed to the central effect of substances released peripherally and entering the nervous system through the blood-brain barrier opened by the implantation procedure, as it could not be found in animals bearing implants of other peripheral endocrine tissue, viz, pituitary. The effect of nicotine was not blocked by the pretreatment of the animals with either the opiate antagonist naloxone (2.5 mg/kg, 10 min) or the dopamine receptor blocker pimozide (0.5 mg/kg, 1 h), although the latter pretreatment blocked the amphetamine-evoked rotation. No spontaneous catecholamine release could be detected from the implanted chromaffin cells by in vivo electrochemistry, while treatment with amphetamine or nicotine did evoke a release. The results suggest that the functional effects of such intrastriatal grafts of chromaffin cells, reported in previous studies, cannot be explained by the secretion from the grafted cells of catecholamines into the denervated striatum. On the other hand the results obtained following the pharmacological stimulation of these cells indicate that adrenal grafts can, under suitable conditions, influence the functioning of the host nervous system.

11/1989 | Pharmacol Biochem Behav   IF 2.5
Septal alpha-noradrenergic antagonism in vivo blocks the testing-induced
Marighetto A, Durkin T, Toumane A, Lebrun C, Jaffard R

In order to test the hypothesis that alpha-noradrenergic receptors in the septum

09/1989 | Behav Neural Biol
The durations of hippocampal and cortical cholinergic activation induced by
Toumane A, Durkin T, Marighetto A, Jaffard R

Sodium-dependent high-affinity choline uptake velocities in P2 fractions of the

1989 | Arch Gerontol Geriatr Suppl   IF 2.2
Experimental dissociation of memory systems in mice: behavioral and neurochemical
Jaffard R, Durkin T, Toumane A, Marighetto A, Lebrun C

Evidence for different types of memory in mice may lead to development of animal

10/1988 | Behav Brain Res   IF 3.2
Differential hippocampal and cortical cholinergic activation during the
Toumane A, Durkin T, Marighetto A, Galey D, Jaffard R

Possible differentiation of the intervention of cholinergic septohippocampal and