Fear Memory in Experimental Models of Parkinson’s Disease

• Published in: Advances in gerontology Vol. 14; no. 1; pp. 1 - 13
• Main Authors: Timofeeva, E. A., Dubrovina, N. I., Tikhonova, M. A., Amstislavskaya, T. G.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-03-2024; Springer Nature B.V
• Subjects: Anxiety; Brain research; Cognitive ability; Disease; Geriatrics/Gerontology; Kinases; Laboratory animals; Medicine; Medicine & Public Health; Memory; Pathogenesis; Quality of life; Review; experimental models; nonmotor symptoms; fear memory; aging; memory trace; Parkinson’s disease; rodents
• ISSN: 2079-0570; 2079-0589
• DOI: 10.1134/S207905702460040X

Parkinson’s disease (PD) is a neurodegenerative disease, the main predisposing factor of which is aging. Today, the majority of people suffering from PD are over 65 years of age. This disease leads to motor and nonmotor deficits, significantly reducing the quality and length of life. One of the symptoms of nonmotor manifestations is a decrease in cognitive function, including impaired memory and learning ability. Fear is a response to a threatening situation that is always real and well defined. Fear memory is a form of memory that remains stable throughout the life of an organism. Using neurotoxic and genetic models of laboratory animals, it is possible to reproduce the symptoms of the disease to decipher the pathological features, genetic factors, and mechanisms underlying PD. In addition, disease modeling makes it possible to study the mechanisms of fear memory for a given disease with assessment of the response of fear conditioning to a given context or sound/light as the conditioned signal (contextual and signal response to fear conditioning), and the conditioned response of passive avoidance. The cognitive and motor symptoms of PD refer to different brain regions. The structures that play a critical role in fear-memory mechanisms are the hippocampus and the amygdala. The hippocampus is responsible for “creating context” and the amygdala is responsible for “creating fear,” and as a result of the convergence of signals, a fear-memory trace is formed. Using mice and rat models of PD, experimental evidence has been obtained for the significant contribution of the hippocampus and amygdala to the mechanisms of fear-memory impairment. In addition, deficits in fear memory in Parkinson-like conditions correlate with α-syn neuropathology (alpha-synuclein deposits) in the hippocampus and amygdala. Dysfunction of the nigrostriatal system through the mechanisms of neuroinflammation and oxidative stress also causes the impairment of fear memory. Thus, the mechanism of fear-memory deficit in PD may be a change in information processing in the hippocampus/prefrontal cortex/amygdala networks due to identified impairment in synaptic plasticity, the development of neuroinflammation, oxidative stress, and α-syn-neuropathology.