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Sparing of orexin‐ A and orexin‐ B neurons in the hypothalamus and of orexin fibers in the substantia nigra of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐treated macaques
Author(s) -
Bensaid Manale,
Tandé Dominique,
Fabre Véronique,
Michel Patrick P.,
Hirsch Etienne C.,
François Chantal
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12761
Subject(s) - substantia nigra , orexin , pars compacta , dopaminergic , ventral tegmental area , medicine , endocrinology , tyrosine hydroxylase , orexin a , hypothalamus , lateral hypothalamus , neuroscience , chemistry , neuropeptide , dopamine , biology , receptor
Several studies conducted in patients with P arkinson's disease have reported that the degeneration of substantia nigra dopaminergic neurons, which are essential for motor control, is associated with the loss of hypothalamic orexin neurons, which are involved in sleep regulation. In order to better explore the mutual interactions between these two systems, we wished to determine in macaques: (i) if the two orexin peptides, orexin‐ A and orexin‐ B , are distributed in the same hypothalamic cells and if they are localized in nerve terminals that project onto nigral dopaminergic neurons, and (ii) if there is a loss of orexin neurons in the hypothalamus and of orexin fibers innervating nigral dopaminergic neurons in macaques rendered parkinsonian by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine ( MPTP ) intoxication. We showed that virtually all cells stained for orexin‐ A in the hypothalamus co‐expressed orexin‐ B . Numerous terminals stained for both orexin‐ A and orexin‐ B immunoreactivity that innervated the whole extent of the ventral tegmental area and substantia nigra pars compacta were found in close proximity to tyrosine hydroxylase‐immunoreactive dendrites. These data indicate that orexin‐ A and orexin‐ B peptides are in a position to play a role in controlling the activity of nigral dopaminergic neurons. However, no loss of orexin‐ A or orexin‐ B neurons in the hypothalamus and no loss of orexin fibers in the substantia nigra pars compacta was found in MPTP ‐treated macaques when compared with control macaques. We conclude that a relatively selective dopaminergic lesion, such as that performed in MPTP ‐treated macaques, is not sufficient to induce a loss of hypothalamic orexin neurons.