Differential impairment of short working and spatial memories in a rat model of progressive Parkinson's disease onset: A focus on the prodromal stage

Abstract

Studying the non-motor disorders of the prodromal phase of Parkinson's disease (PD) is of great importance because of their negative impact on patient's quality of life. Classical neurotoxic animal models of PD generally unable the exploration of the progression of the non-motor phase of the prodromal stage of the disease. The aim of this study is to assess the evolution of two types of memory alteration namely; short working and spatial memories at different stages of the prodromal phase of a rat model of PD, using repetitive reserpine administration at low dose. The study was carried out in rat with repeated i.p reserpine administration (0.2 mg/kg/day) during 13 days. Working memory was assessed by the Novel Object Recognition test (NOR) and the T-maze, while spatial memory was assessed by Morris Water maze (MWM) at to stages (7days and 13days) of prodromal phase of the disease. By means of immunohistochemistry, the serotonergic innervation of the Baso-Lateral Amygdala nucleus (BLA) as well as the morphological changes of astroglia within hippocampus (using anti-GFAP marker) were examined at the latest stage (13days) of the disease. Our data show a differential deterioration of short-term working memory without the long-term spatial memory being changed which was accompanied by a significant decrease in serotonin innervation of the BLA and a striking change in both density and morphology of the astrocyte at the level of the hippocampus. The present study has brought evidence of an early deficit of short working memory rather than spatial memory deficit which seems to be intact even at the latest stage of the prodromal phase of PD. Such deficit could arise from the loss of 5-HT innervation in BLA and/or the astroglial morpho-functional changes within the hippocampus leading to possible neurophysiological disturbances of the different neighboring neuronal populations involved in short working memory.

Keywords: 5-HT; Astroglia; Long-term spatial memory; Parkinson’s disease; Prodromal phase; Rat; Reserpine; Short-term working memory.