Contribution of the GABAergic System to Non-Motor Manifestations in Premotor and Early Stages of Parkinson’s Disease

Non-motor symptoms are common in Parkinson's disease (PD) and they represent a major source of disease burden. Several non-motor manifestations, such as rapid eye movement sleep behavior disorder, olfactory loss, gastrointestinal abnormalities, visual alterations, cognitive and mood disorders, are known to precede the onset of motor signs. Nonetheless, the mechanisms mediating these alterations are poorly understood and probably involve several neurotransmitter systems. The dysregulation of GABAergic system has received little attention in PD, although the spectrum of non-motor symptoms might be linked to this pathway. This Mini Review aims to provide up-to-date information about the involvement of the GABAergic system for explaining non-motor manifestations in early stages of PD. Therefore, special attention is paid to the clinical data derived from patients with isolated REM sleep behavior disorder or drug-naive patients with PD, as they represent prodromal and early stages of the disease, respectively. This, in combination with animal studies, might help us to understand how the disturbance of the GABAergic system is related to non-motor manifestations of PD.This study was partially funded by the Michael J. Fox Foundation (2014 Rapid Response Innovation Awards; Grant 10189), the Carlos III Health Institute through Projects PI14/00679 and PI16/00005, and a Juan Rodes Grant (JR15/00008) (I.G.) (cofunded by the "Investing in Your Future" European Regional Development Fund/European Social Fund programme), the Department of Health of the Basque Government through Project 2016111009, and EITB/BIOEF telemarathon for Neurodegenerative Diseases (BIO17/ND/010/BC)