Differentiation of rat hypothalamic dopaminergic neurons is stimulated in vitro by target cells: the melanotrophs

Abstract

We have investigated in vitro the influence of pituitary intermediate lobe melanotrophs on the differentiation of their afferent hypothalamic dopaminergic neurons. The presence of melanotrophs in primary cultures of foetal hypothalamic neurons induces an increase of the number of dopaminergic neurons (while the total neuronal population remains unchanged) and induces a stimulation of their neuritic outgrowth. These effects are mediated by diffusible factors since they are reproduced by application of conditioned medium issued from co-cultures with intermediate lobe cells from newborn rats. Moreover, by immunoneutralization of alpha-melanocyte-stimulating hormone (alphaMSH) in the co-culture or conditioned medium, or by application of the peptide itself, we demonstrate that the neuritotrophic effect on dopaminergic neurons is mediated by alphaMSH, the main secretory product of melanotrophs, whereas the inductive effect on the number of dopaminergic neurons is attributable to another diffusible neurotrophic factor(s) present in foetal, but not adult, adenohypophysis. Similar effects are observed on cultures of newborn hypothalamic neurons. However, at this stage of neuronal development, alphaMSH also increases the number of dopaminergic neurons, which could be due to a change of neuronal receptivity. We show that the neuritotrophic influence of alphaMSH is restricted to the dopaminergic neurons connected to the melanotrophs, and that in addition, these neurons systematically co-express the tyrosine hydroxylase and glutamate decarboxylase as the neurons innervating the melanotrophs in situ. These findings indicate that the differentiation of dopaminergic hypothalamic neurons is influenced by the target cells, melanotrophs, and that this trophic influence implicates alphaMSH.

Neonatal melanocortin receptor agonist treatment reduces play fighting and promotes adult attachment in prairie voles in a sex-dependent manner

“…In addition to impacting hypothalamic neuropeptide systems, MC4R signaling has been linked to dopaminergic and opioid-mediating reward and reinforcement systems, which are critically involved in pair bond formation (Burkett and Young, 2012). Alpha-MSH or MTII stimulates dopamine release in the ventral tegmental area through MC4R activation (Lindblom et al, 2001), alters dopamine receptor expression in the nucleus accumbens and tegmentum (Lindblom et al, 2002), modifies accumbal D1R signaling in response to stress (Lim et al, 2012), and influences hypothalamic dopamine neuron differentiation (Egles et al, 1998). The rewarding and addictive effects of cocaine and opiates are thought to be mediated by MC4R signaling (Alvaro et al, 1996; Alvaro et al, 1997; Hsu et al, 2005).…”

“…Interestingly, neonatal administration of α-MSH and ACTH-like peptides to rats leads to enhancements in adult attention to relevant stimuli (Champney et al, 1976), learning (Beckwith et al, 1977b; Acker et al, 1985), social contact in an open field (Beckwith et al, 1977a), and reductions in adult anxiety (Felszeghy et al, 1993). Early α-MSH treatment also impacts hypothalamic cytoskeletal proteins (Wu et al, 2006), hypothalamic dopamine neuron development (Egles et al, 1998), and neurite outgrowth (Joosten et al, 1996), thus leading to functional and structural changes in neural development. As MC agonists impact a variety of neural systems involved in sociality and acute MC4R stimulation promotes adult pair bonding, early MC stimulation may also stimulate encoding of early social information and lead to long-term organizational changes in social behavior.…”

Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity

“…These neurons have been shown to co-localize or interact with TH-expressing cells in different regions of the hypothalamus, although it has not been reported whether they co-express TH. 64 , 65 , 66 , 67 , 68 Examining the transcriptomic profiles of these cell types can reveal their roles in hypothalamus function.…”

Induction of proopiomelanocortin mRNA expression in animal caps of Xenopus laevis embryos

“…As POMC is expressed very early during development, this prohormone or POMC‐derived peptides may constitute a factor involved in the differentiation of the pituitary cell types expressing other pituitary hormones. Moreover, POMC might be important for the development of the overlying hypothalamus, as in vitro differentiation of rat hypothalamic dopaminergic neurons can be stimulated by POMC‐derived peptide αMSH ( Egles et al 1998 ). It does appear that a factor from the pituitary (e.g.…”