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The weaning period promotes alterations in the orexin neuronal population of rats in a suckling-dependent manner


The orexin-immunoreactive neurons are part of an important arousal-promoting hypothalamic population. Several groups have investigated these neurons during the lactation period, when numerous physiological alterations occur in the dam’s body to cope with the newly acquired metabolic needs of the litter. Although those studies have probed this population during the early and intermediate stages of lactation, few works have examined its response to weaning, including the cessation of the tactile suckling stimulus as the litter stops nursing. Using double immunohistochemistry for orexin and FOS combined with three-dimensional reconstruction techniques, we investigated orexin-synthesizing neurons and their activation at different times during weaning, in addition to the role played by the suckling stimulus. We report here that weaning promoted a decline in the anterior population of orexin-immunoreactive neurons and decreased the number of double orexin–FOS neurons labeled in the central dorsomedial hypothalamus, in addition to reducing the overall number of FOS-immunoreactive cells in the whole tuberal hypothalamus. Disruption of the suckling stimulus from the pups impaired the decrease in the number of anteriorly located orexin-immunoreactive neurons, attenuated the activation of orexin-synthesizing cells in the dorsomedial hypothalamus and reduced the number of FOS-immunoreactive neurons across the tuberal hypothalamus. When taken together, our data suggest that the weaning period is necessary to restore neurochemical pathways altered during the lactation period and that the suckling stimulus plays a significant role in this process.

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This article was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation—FAPESP) grants #2016/02748-0 (GD), #2017/17998-5 (MK), #2010/52068-0, #2016/02224-1 and #2017/08908-2 (JB). J-LN and JB are also recipients of a joint Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Agency for the Advancement of Higher Education) and Comité Français d’Evaluation de la Coopération Universitaire avec le Brésil (French Committee for the Evaluation of Academic and Scientific Cooperation with Brazil) grant CAPES|COFECUB 848/15. J-LN and FP were supported by the French Centre National de la Recherche Scientifique (The National Center for Scientific Research—CNRS) and the French Agence Nationale de la Recherche (National Research Agency—ANR) through the LABEX SIGNALIFE program #ANR-11-LABX-0028-01. LF and JB are Investigators with the Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development—CNPq) with grants #305481/2016-9 (LF) and #426378/2016-4 (JC).

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Correspondence to Jackson C. Bittencourt.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Diniz, G.B., Candido, P.L., Klein, M.O. et al. The weaning period promotes alterations in the orexin neuronal population of rats in a suckling-dependent manner. Brain Struct Funct 223, 3739–3755 (2018).

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  • Hypocretin
  • Hypothalamus
  • Neuropeptides
  • Sleep
  • Wakefulness
  • Lactation