Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0036341 (
schizophrenia
)
60,220
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The regulation of the striatum by the GPCR signaling through neuromodulators is essential for its physiology and physiopathology, so it is necessary to know all the compounds of these pathways. In this study, we identified a new important partner of the dopaminergic pathway:
GPRIN3
(a member of the GPRIN family).
GPRIN3
is highly expressed in the striatum but with undefined function. Cell sorting of medium spiny neurons (MSNs) in indirect MSNs and direct MSNs indicated the presence of the
GPRIN3
gene in both populations with a preferential expression in indirect MSNs. This led us to generate
GPRIN3
KO mice by CRISPR/Cas9 and test male animals to access possible alterations in morphological, electrophysiological, and behavioral parameters following its absence. 3D reconstruction analysis of MSNs revealed increased neuronal arborization in
GPRIN3
KO and modified passive and active electrophysiological properties. These cellular alterations were coupled with increased motivation and cocaine-induced hyperlocomotion. Additionally, using a specific indirect MSN knockdown, we showed a preferential role for
GPRIN3
in indirect MSNs related to the D
2
R signaling. Together, these results show that
GPRIN3
is a mediator of D
2
R function in the striatum playing a major role in striatal physiology.
SIGNIFICANCE STATEMENT
The striatum is the main input of the basal ganglia processing information from different brain regions through the combined actions of direct pathway neurons and indirect pathway neurons. Both neuronal populations are defined by the expression of dopamine D
1
R or D
2
R GPCRs, respectively. How these neurons signal to the respective G-protein is still debatable. Here we identified
GPRIN3
as a putative selective controller of D
2
R function in the striatum playing a critical role in striatal-associated behaviors and cellular functions. This study represents the identification of a new target to tackle striatal dysfunction associated with the D
2
R, such as
schizophrenia
, Parkinson's disease, and drug addiction.
...
PMID:GPRIN3 Controls Neuronal Excitability, Morphology, and Striatal-Dependent Behaviors in the Indirect Pathway of the Striatum. 3136 62
