Non-motor symptoms in Parkinson's disease (PD) have been often described at different stages of the disease and seem to be influenced by gender. We observed specific phenotypes resembling 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 has been shown to be a substrate of parkin and to be involved in the pathogenesis of PD. In previous reports GPR37 knock-out (KO) mice were reported to exhibit several motor behavioral abnormalities related to altered dopaminergic system function. We have shown that GPR37 interacts with the dopamine transporter (DAT), modulating its presynaptic functional expression, striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine. To evaluate other non-motor behavioral domains (autonomic and sensory functions, anxiety and depression, cognitive functions) adult and aged, male and female GPR37 KO mice and their wild-type (WT) littermates were used in a series of crosssectional studies. Mild deficits were observed in olfactory function of mutant mice tested in the block and habituation to non-social odors tests as well as in their colonic motility function. Anxiety and depression-like behaviors appeared to be significantly increased in aged GPR37 KO female mice, in the elevated plus maze and forced swimming tests. While no differences were detected in fear conditioned freezing and pre-pulse inhibition, a significant reduction of the startle response to acoustic stimuli was observed in adult GPR37 KO mice of both genders. Furthermore, HPLC analysis of major neurotransmitter levels revealed significant gender differences in the striatum and olfactory bulbs of mutant mice. The study of non-motor behavioral impairments in GPR37 mutant mice could elucidate the possible role of this receptor in modulating various symptoms observed in PD and also extend the understanding of gender and age influences on these type of distressing symptoms.
Non-motor behavioral impairments depend on age and gender in mice lacking the Parkinson's disease related GPR37/Pael receptor
Mandillo S;Golini E;Marazziti D;Di Pietro C;Matteoni R;
2011
Abstract
Non-motor symptoms in Parkinson's disease (PD) have been often described at different stages of the disease and seem to be influenced by gender. We observed specific phenotypes resembling 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 has been shown to be a substrate of parkin and to be involved in the pathogenesis of PD. In previous reports GPR37 knock-out (KO) mice were reported to exhibit several motor behavioral abnormalities related to altered dopaminergic system function. We have shown that GPR37 interacts with the dopamine transporter (DAT), modulating its presynaptic functional expression, striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine. To evaluate other non-motor behavioral domains (autonomic and sensory functions, anxiety and depression, cognitive functions) adult and aged, male and female GPR37 KO mice and their wild-type (WT) littermates were used in a series of crosssectional studies. Mild deficits were observed in olfactory function of mutant mice tested in the block and habituation to non-social odors tests as well as in their colonic motility function. Anxiety and depression-like behaviors appeared to be significantly increased in aged GPR37 KO female mice, in the elevated plus maze and forced swimming tests. While no differences were detected in fear conditioned freezing and pre-pulse inhibition, a significant reduction of the startle response to acoustic stimuli was observed in adult GPR37 KO mice of both genders. Furthermore, HPLC analysis of major neurotransmitter levels revealed significant gender differences in the striatum and olfactory bulbs of mutant mice. The study of non-motor behavioral impairments in GPR37 mutant mice could elucidate the possible role of this receptor in modulating various symptoms observed in PD and also extend the understanding of gender and age influences on these type of distressing symptoms.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
