Spexin and Galanin in Metabolic Functions and Social Behaviors With a Focus on Non-Mammalian Vertebrates

Abstract

Spexin (SPX) and galanin (GAL) are two neuropeptides that are phylogenetically related and have descended from a common ancestral gene. Considerable attention has been given to these two multifunctional neuropeptides because they share GAL receptors 1,2, and 3. Since GAL and SPX-synthesizing neurons have been detected in several brain areas, therefore, it can be speculated that SPX and GAL are involved in various neurophysiological functions. Several studies have shown the functions of these two neuropeptides in energy regulation, reproduction, and response to stress. SPX acts as a satiety factor to suppress food intake, while GAL has the opposite effect as an orexigenic factor. There is evidence that SPX acts as an inhibitor of reproductive functions by suppressing gonadotropin release, while GAL modulates the activity of gonadotropin-releasing hormone (GnRH) neurons in the brain and gonadotropic cells in the pituitary. SPX and GAL are responsive to stress. Furthermore, SPX can act as an anxiolytic factor, while GAL exerts anti-depressant and pro-depressive effects depending on the receptor it binds. This review describes evidence supporting the central roles of SPX and GAL neuropeptides in energy balance, reproduction, stress, and social behaviors, with a particular focus on non-mammalian vertebrate systems.

Long‐term enhancements in antidepressant efficacy and neurogenesis: Effects of intranasal co‐administration of neuropeptide Y 1 receptor (NPY1R) and galanin receptor 2 (GALR2) agonists in the ventral hippocampus

“…GALP and spexin have been implicated in a variety of biological processes, including modulation of mood, appetite, and energy homeostasis, which are relevant to the understanding of mood disorders. 34,35 The interaction between NPY and GAL, particularly through the formation of NPY1R-GALR2 heteroreceptor complexes, represents a novel and complex mechanism of neuromodulation in the brain. These heteroreceptor complexes enable cross-talk between NPY and GAL signaling pathways, potentially amplifying or modulating the effects of each neuropeptide on mood regulation.…”

New evidence for SPX2 in regulating the brain-pituitary reproductive axis of half-smooth tongue sole (Cynoglossus semilaevis)

“…Spexin (SPX), also termed neuropeptide Q (NPQ) or C12ORF39, is a novel hypothalamic neuropeptide that was first identified by bioinformatics approach ( 1 , 2 ) , and subsequently its orthologs have been found from fish to mammals ( 3 – 5 ). The SPX mature peptide is a tetradecapeptide that is flanked by two dibasic protein cleavage sites (RR and GRR), and its amino acid sequence is highly conserved in various vertebrates, with only one amino acid substitution at position 13 between tetrapods and teleosts ( 3 – 5 ).…”

“…Spexin (SPX), also termed neuropeptide Q (NPQ) or C12ORF39, is a novel hypothalamic neuropeptide that was first identified by bioinformatics approach ( 1 , 2 ) , and subsequently its orthologs have been found from fish to mammals ( 3 – 5 ). The SPX mature peptide is a tetradecapeptide that is flanked by two dibasic protein cleavage sites (RR and GRR), and its amino acid sequence is highly conserved in various vertebrates, with only one amino acid substitution at position 13 between tetrapods and teleosts ( 3 – 5 ). Consistent with its widespread distribution in different tissues of teleosts and other vertebrates, SPX participates in a variety of physiological functions, such as glucose homeostasis, lipid metabolism, feeding, digestion, reproduction, among others ( 6 – 10 ).…”

“…Interestingly, Nile tilapia and other cichlid fish species have two SPX1 paralogs (SPX1a and SPX1b) but have no SPX2 ( 12 ). In teleosts, the physiological functions of SPX are just emerging, and mainly focus on the control of reproduction and appetite ( 3 – 5 ). For instance, in vivo and in vitro administration of SPX1 suppress LH secretion in goldfish ( 14 ), and both LH and FSH plasma levels are significantly reduced after a single intraperitoneal injection of SPX1a or SPX1b in Nile tilapia ( 12 ).…”

“…Moreover, overexpression of SPX1 in the dorsal habenula reduces anxiety in zebrafish ( 23 ). On the other hand, no information is available regarding the biological role of SPX2 in any vertebrate, other than two studies on the SPX2-Galr2/3 interaction and detailed brain distribution of SPX2 in zebrafish ( 3 – 5 ). The serum response element-driven luciferase (SRE-luc) activity is significantly elevated by zebrafish SPX2 in HEK293 cells expressing zebrafish, Xenopus , and human Galr2 or Galr3, suggesting that SPX2 is an endogenous ligand for Galr2/3 ( 11 ).…”