The Central Mechanisms of Secretin in Regulating Multiple Behaviors

Abstract

Secretin (SCT) was firstly discovered as a gut peptide hormone in stimulating pancreatic secretion, while its novel neuropeptide role has drawn substantial research interests in recent years. SCT and its receptor (SCTR) are widely expressed in different brain regions, where they exert multiple cellular functions including neurotransmission, gene expression regulation, neurogenesis, and neural protection. As all these neural functions ultimately can affect behaviors, it is hypothesized that SCT controls multiple behavioral paradigms. Current findings support this hypothesis as SCT–SCTR axis participates in modulating social interaction, spatial learning, water and food intake, motor coordination, and motor learning behaviors. This mini-review focuses on various aspects of SCT and SCTR in hippocampus, hypothalamus, and cerebellum including distribution profiles, cellular functions, and behavioral phenotypes to elucidate the link between cellular mechanisms and behavioral control.

Secretin Modulates the Postnatal Development of Mouse Cerebellar Cortex Via PKA- and ERK-dependent Pathways

“…SCT was initially noted to stimulate pancreatic secretion, and later was shown to exert pluripotent roles in regulating various behaviors including feeding, water drinking, and even spatial memory in central nervous system (reviewed in Zhang and Chow, 2014 ). Our previous study demonstrated the requirement of PC-specific SCT in maintaining intact motor coordination and motor learning function in mice (Zhang et al, 2014 ).…”

In vivo actions of SCTR/AT1aR heteromer in controlling Vp expression and release via cFos/cAMP/CREB pathway in magnocellular neurons of PVN

“…GPCRs are major drug targets, constituting more than 50% of existing therapeutic agents (5). SCTR is prototypical of class B GPCRs (42), and we have recently established its role in lipid metabolism (43), water and salt homeostasis (14), and motor control and learning (44). Together with the SCTR's role in gut pH (45) and insulin secretion (46), SCT/SCTR has diverse roles that make it a potential drug target.…”

The Potential Role of Gut Peptide Hormones in Autism Spectrum Disorder

“…Several lines of evidence from rodent and human studies show that secretin and its receptors are widely distributed in the brain areas from cerebral cortex, hippocampus, amygdala, hypothalamus to cerebellum (Yuan et al, 2011;Wang et al, 2019). The neurological functions of secretin are also being gradually explored by molecular, physiological and behavioral approaches (Zhang and Chow, 2014;Wang et al, 2019).…”

“…Those secretory factors have been recognized for their roles in modulating GI functions and body energy metabolism. In recent 20∼30 years, their brain functions are being gradually revealed from molecular, behavioral and physiological evidence (Zhang and Chow, 2014;Donahue et al, 2016;Kingsbury and Wilson, 2016). For example, CCK and VIP are now working as markers for specific sub-population of neurons having unique morphological features of axon collaterals and firing patterns (Kawaguchi and Kondo, 2002).…”