Sensitivity to the photoperiod and potential migratory features of neuroblasts in the adult sheep hypothalamus

Abstract

Adult neurogenesis, a process that consists in the generation of new neurons from adult neural stem cells, represents a remarkable illustration of the brain structural plasticity abilities. The hypothalamus, a brain region that plays a key role in the neuroendocrine regulations including reproduction, metabolism or food intake, houses neural stem cells located within a hypothalamic neurogenic niche. In adult sheep, a seasonal mammalian species, previous recent studies have revealed photoperiod-dependent changes in the hypothalamic cell proliferation rate. In addition, doublecortin (DCX), a microtubule-associated protein expressed in immature migrating neurons, is highly present in the vicinity of the hypothalamic neurogenic niche. With the aim to further explore the mechanism underlying adult sheep hypothalamic neurogenesis, we first show that new neuron production is also seasonally regulated since the density of DCX-positive cells changes according to the photoperiodic conditions at various time points of the year. We then demonstrate that cyclin-dependant kinase-5 (Cdk5) and p35, two proteins involved in DCX phosphorylation and known to be critically involved in migration processes, are co-expressed with DCX in young hypothalamic neurons and are capable of in vivo interaction. Finally, to examine the migratory potential of these adult-born neurons, we reveal the rostro-caudal extent of DCX labeling on hypothalamic sagittal planes. DCX-positive cells are found in the most rostral nuclei of the hypothalamus, including the preoptic area many of which co-expressed estrogen receptor-α. Thus, beyond the confirmation of the high level of neuron production during short photoperiod in sheep, our results bring new and compelling elements in support of the existence of a hypothalamic migratory path that is responsive to seasonal stimuli.

A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance

“…In the Syrian hamster ( Mesocricetus auratus ), BrdU incorporation into tanycytes, as a marker for cell proliferation, is affected by photoperiod18 and equally in F344 rats and sheep more cells are generated in SD as compared to LD1517. In Siberian hamsters ( Phodopus sungorus ) and sheep, adaptations of neural pathways as well as cell structure and morphological changes in the hypothalamus are also associated with changes in photoperiod14161920. Taken together these data suggest that structural changes within the hypothalamus may be at the core of the long-term effects of photoperiod on physiology, such as regulation of energy balance and body weight.…”

Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems

“…In addition to feeding control, studies in seasonal mammals support a role for hypothalamic neurogenesis in the control of reproduction (Batailler et al 2015;Ebling 2015). Moreover, there is now evidence that systemic aging is initiated by hypothalamic inflammation ).…”

Stem Cells in Neuroendocrinology

“…In addition to feeding control, studies in seasonal mammals support a role for hypothalamic neurogenesis in the control of reproduction (Batailler et al 2015;Ebling 2015). Moreover, there is now evidence that systemic aging is initiated by hypothalamic inflammation .…”

“…Newborn neurons in the postnatal and adult hypothalamus have been described in multiple vertebrate species, including zebrafish McPherson et al 2016), chick (Kisliouk et al 2014), hamster (Mohr and Sisk 2013), mouse (Lee et al 2012), rats (Matsuzaki et al 2015), and sheep (Batailler et al 2015). This finding suggests a degree of plasticity that is evolutionarily conserved and likely extends to humans as well (Batailler et al 2013;Dahiya et al 2011;Noguiera et al 2014).…”