Download Functional roles of melanocortin-4 receptor in hippocampal synapse

Registration ID :s428100050A
Functional
roles
of
melanocortin-4
receptor
in
hippocampal synapse
Yang SHEN, Wing-Yu FU, Amy K. Y. FU, Nancy Y. IP
*
Division of Life Science, Molecular Neuroscience Center and State Key
Laboratory of Molecular Neuroscience, The Hong Kong University of Science and
Technology, Clear Water Bay, Hong Kong, China
*Corresponding author
E-mail:[email protected]
Abstract: Objective Melanocortin-4 receptor (MC4R), which belongs to the Gprotein coupled receptor (GPCR) superfamily, is one of the five melanocortin
receptors (MCRs) that is expressed abundantly in the central nervous system.
MC4R
is
activated
by
various
endogenous
ligands
including
melanocyte
stimulating hormone (MSH), and adrenocorticotropin hormones. The central
melanocortin signaling in the hypothalamus–pituitary-adrenal axis system is
critical for regulating various aspects of energy homeostasis and feeding
behavior. Although MC4R is highly expressed in other brain regions such as
cortex and hippocampus, the roles of MC4R in these regions remain elusive. In
this study, the functional role of MC4R in synapse plasticity in hippocampus is
examined. Methods The regulation of MC4R protein in hippocampal neurons was
examined using immunocytochemical analysis and Western blot analysis.
The
function of MC4R in hippocampal neurons was studied by RNA interference using
calcium phosphate transfection. Results (1) MC4R protein increases in rat
hippocampus upon development and enriched at the synaptic compartment.
(2)
Knockdown of MC4R in cultured rat hippocampal neurons results in a regulation
in the density of dendritic spines, the sites where excitatory synapses reside.
(3) Stimulation of MC4R increases the cAMP level in hippocampal neurons.
Conclusion
MC4R
regulates
the
synapse
functions
through
modulating
the
morphology of dendritic spines.
Keywords: Melanocortin-4 receptor, cyclic AMP, dendritic spines
This study was supported in part by the Research Grants Council of Hong Kong
SAR (660309, 661109) and the Area of Excellence Scheme of the University Grants
Committee (AoE/B-15/01).