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The Ghrelin Receptor Regulates Dendritic Spines and the NMDA Receptor–Mediated Synaptic Transmission in the Hippocampus

Year: 2017
Type: book-chapter
Abstract: Increasing evidence suggests the involvement of ghrelin (an orexigenic hormone) and its cognate receptor growth hormone secretagogue receptor (GHSR1a, also known as the ghrelin receptor) in extra‐hypothalamic functions such as hippocampal learning and memory. However, cellular and molecular mechanisms underlying the ghrelin‐regulated hippocampal neuron activity are poorly understood. In this chapter, we show the following: (1) ghrelin promoted phosphorylation of the N‐methyl‐d‐aspartate receptor (NMDAR) subunit 1 (GluN1) in a PKC/PKA‐dependent manner and amplified NMDAR‐mediated excitatory postsynaptic currents, (2) ghrelin stimulated phosphorylation of CREB (cAMP response‐element‐binding protein), and (3) ghrelin increased phalloidin binding to F‐actin, suggesting possible reorganization of dendritic spines; all occurred through the activation of GHSR1a in the CA1 pyramidal cell of the hippocampus in cultured slice preparations. Interestingly, the ghrelin’s effects on GluN1 and CREB phosphorylation were negatively modulated by exogenous application of endocannabinoids, 2‐arachidonoylglycerol (2‐AG), and anandamide (ANE), in type 1 cannabinoid receptor (CB1R)‐dependent and ‐independent manners, respectively. It is suggested that ghrelin and the ghrelin receptor regulate synaptic transmission and plasticity in the hippocampus, interacting with the endogenous cannabinoid system, which may be essential and necessary for successful acquisition of metabolic state–dependent learning and adaptive appetitive behavior.
DOI: 10.5772/65704
Language: English
Open Access status: hybrid
OpenAlex ID: W2634250586
FWCI:
Cites: 41
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Related to: 10