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Implication des angiotensines cérébrales dans la maturation postnatale du phénotype tyrosine hydroxylase dans les neurones noradrénergiques bulbo-pontiques chez le rat

Abstract : The regulation of the dendritic transport of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, could precisely modulate the extent of the cerebral field subjected to catecholaminergic influence, and thus could modulate many neurovegetative and central functions. This type of regulation was particularly observed in nucleus tractus solitarius (NTS) and locus coeruleus (LC) catecholaminergic neurons, without any clues about molecular and cellular factors involved in vivo. Here, we have observed whether cerebral angiotensins are involved in this regulation, using TGR(ASrAOGEN)680 (TGR) rat strain, characterized by an inhibition of the synthesis of the only known precursor for all cerebral angiotensins, the astrocytic angiotensinogène. We have observed a sharp decrease of TH quantity within NTS and LC in these rats, specifically during the 4th postnatal week. This phenomenon is particularly characterized by a sharp accumulation of TH protein within cell bodies of NTS and LC neurons and by a blockade of TH dendritic transport, while TH transport toward axonal processes to terminal fields is maintained. The blockade of the dendritic transport of TH protein is associated to an inhibition of the phosphorylation process of MARCKS protein, which is an intracellular signalling pathway that is activated by angiotensins specific AT1 receptors and that was clearly connected in vitro to the neuritic transport of TH protein. The study of the distribution of TH protein within LC terminal fields at adulthood shows the existence of a catecholaminergic hyper-innervation of the dentate gyrus and of frontal and cingular cortices in TGR, which is most probably implicated in the alterations of the durations of sleep-wake stages and of the reactivity of rats to a novelty stress that we have observed in these rats. Thus, our work reveals that cerebral angiotensins are required during the 4th postnatal week to trigger the dendritic transport of TH protein within noradrenergic neurons, and then in the functional setting-up of the inhibitory retrocontrol exerted by the noradrenaline locally released by dendrites of these neurons
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https://tel.archives-ouvertes.fr/tel-00012030
Contributor : Frédérique Cohen-Adad <>
Submitted on : Friday, March 24, 2006 - 2:36:09 PM
Last modification on : Wednesday, November 20, 2019 - 3:06:57 AM
Long-term archiving on: : Saturday, April 3, 2010 - 11:02:10 PM

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  • HAL Id : tel-00012030, version 1

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Michaël Ogier. Implication des angiotensines cérébrales dans la maturation postnatale du phénotype tyrosine hydroxylase dans les neurones noradrénergiques bulbo-pontiques chez le rat. Physiologie [q-bio.TO]. Université Claude Bernard - Lyon I, 2004. Français. ⟨tel-00012030⟩

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