Impairment to Cognitive Functions in Wistar Rats in a Model of the Preclinical Stage of Parkinson’s Disease

Autor: Yu. F. Pastukhov, I. V. Ekimova, M. V. Chernyshev, A. V. Matsulevich, N. N. Abdurasulova
Rok vydání: 2020
Předmět:
Zdroj: Neuroscience and Behavioral Physiology. 50:439-450
ISSN: 1573-899X
0097-0549
Popis: The preclinical stage of Parkinson’s disease (PD), when most dopaminergic neurons in the nigrostriatal system of the brain are still intact and compensatory mechanisms have not yet been overwhelmed, is the most effective “therapeutic window.” Much attention in recent years has therefore been focused on seeking early markers for the neurodegenerative process and developing experimental models. The present study addressed the task of analyzing early behavioral changes reflecting impairments in the cognitive and affective domains on modeling the premotor stage of PD in rats, with identification of the most informative tests. A model developed in our laboratory is based on a prolonged (21 days) preclinical stage of PD in rats by increasing suppression of the ubiquitin-proteasome system of the brain induced by two intranasal doses of the specific proteasome inhibitor lactacystin. Cognitive impairments were assessed using the novel object recognition and Y maze tests and the what–where–when paradigm. Anxiety was assessed in the elevated plus maze and open field tests. Administration of lactacystin was found to degrade spatial memory, episodic memory, and recognition of novel objects in rats on the background of a transient increase in the level of anxiety. These data suggest that impairments in the cognitive and affective domains may be early signs of the development of neurodegeneration in the brain.
Databáze: OpenAIRE