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Publication : Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect.

First Author  Mandillo S Year  2013
Journal  Genes Brain Behav Volume  12
Issue  4 Pages  465-77
PubMed ID  23574697 Mgi Jnum  J:213299
Mgi Id  MGI:5584063 Doi  10.1111/gbb.12041
Citation  Mandillo S, et al. (2013) Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect. Genes Brain Behav 12(4):465-77
abstractText  Non-motor symptoms in Parkinson's disease (PD) have been often described at different stages of the disease but they are poorly understood. We observed specific phenotypes related to these symptoms in mice lacking the PD-associated GPR37/PAEL receptor. GPR37 is an orphan G-protein-coupled receptor highly expressed in the mammalian central nervous system. It is a substrate of parkin and it is involved in the pathogenesis of PD. GPR37 interacts with the dopamine transporter (DAT), modulating nigro-striatal dopaminergic signaling and behavioral responses to amphetamine and cocaine. GPR37 knockout (KO) mice are resistant to MPTP and exhibit several motor behavioral abnormalities related to altered dopaminergic system function. To evaluate non-motor behavioral domains, adult and aged, male and female GPR37 KO mice and their wild-type (WT) littermates were analyzed in a series of cross-sectional studies. Aged GPR37 KO female mice showed mild improvements in olfactory function, while anxiety and depression-like behaviors appeared to be significantly increased. A reduction of the startle response to acoustic stimuli was observed only in adult GPR37 KO mice of both genders. Furthermore, HPLC analysis of major neurotransmitter levels revealed gender differences in the striatum, hippocampus and olfactory bulb of mutant mice. The absence of GPR37 receptor could have a neuroprotective effect in an age and gender-dependent manner, and the study of this receptor could be valuable in the search for novel therapeutic targets.
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