TY - JOUR

T1 - Fear Memory in Experimental Models of Parkinson’s Disease

AU - Timofeeva, E. A.

AU - Dubrovina, N. I.

AU - Tikhonova, M. A.

AU - Amstislavskaya, T. G.

N1 - The work was carried out at the expense of the Federal Budget for Fundamental Scientific Research (topic no. 122042700001-9).

PY - 2024/3

Y1 - 2024/3

N2 - 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.

AB - 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.

KW - Parkinson’s disease

KW - aging

KW - experimental models

KW - fear memory

KW - memory trace

KW - nonmotor symptoms

KW - rodents

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85197470784&origin=inward&txGid=46e62bef75a76c6ec09707d981c1372c

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001260421600001

UR - https://www.mendeley.com/catalogue/1c6724cf-8d7d-3944-8735-2071553aaa3d/

U2 - 10.1134/S207905702460040X

DO - 10.1134/S207905702460040X

M3 - Article

VL - 14

SP - 1

EP - 13

JO - Advances in Gerontology

JF - Advances in Gerontology

SN - 2079-0589

IS - 1

ER -