Increased Mmp/Reck Expression Ratio Is Associated with Increased Recognition Memory Performance in a Parkinson's Disease Animal Model.

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Among its non-motor symptoms, sleep disorders are extremely common, being linked to cognitive and memory disruption. The microenvironment, particularly the extracellular matrix (ECM), is deeply involved in memory consolidation as well as in neuropathological processes, such as inflammation, damage to the blood-brain barrier and neuronal death. To better understand ECM dynamics in PD memory disturbances, we investigated the orchestrated expression of Mmps (Mmp-3, Mmp-7, and Mmp-9) and their modulators (Reck and Timp-3) in a rotenone-induced PD model. Also, we introduced an additional intervention in the memory process through rapid eye movement sleep deprivation (REMSD). We observed a REMSD-induced trend in reversing the memory impairment caused by rotenone administration. Associated to this phenotype, we observed a significant increase in Mmp-7/Reck and Mmp-9/Reck mRNA expression ratio in the substantia nigra and Mmp-9/Reck ratio in the hypothalamus. Moreover, the positive correlation of Mmp/Reck expression ratios between the substantia nigra and the striatum, observed upon rotenone infusion, was reversed by REMSD. Taken together, our results suggest a potential orchestrated association between an increase in Mmp-7 and Mmp-9/Reck expression ratios in the substantia nigra and a possible positive effect on cognitive performance in subjects affected by PD.