BEHAVIOURAL RESPONSES TO MISMATCH NOVELTY ARE ALTERED UPON AGING IN THE RAT: CORRELATION WITH HIPPOCAMPAL, PREFRONTAL CORTEX AND STRIATAL MONOAMINERGIC MARKERS

Age-related impairment in cognition is still incompletely understood. We investigated the impact of aging on rat mismatch novelty (MN) responses and monoaminergic synaptic function in key brain regions for decision-making, attention, memory and executive function (hippocampus, HIPP; prefrontal cortex, PFC and striatum, STR) and how MN training (MNT), previously shown to influence hippocampal synaptic plasticity¹, impacted learning and memory tasks.
Male Wistar rats aged 3 to 21 months were subjected to the MN test and MNT as described^1,2. Reference and working memory were evaluated using the radial-arm maze (RAM). The levels of general (synaptophysin), GABAergic (gephyrin, GAT-1), glutamatergic (PSD-95) and monoaminergic (SERT, DAT, NET) synaptic markers were evaluated by western-blot in total PFC, STR and HIPP membranes². Animal handling was according to EU laws.
Rat responses to MN were progressively diminished from early adulthood (3-4M) to middle-age (12M) as given by nose pokes (21.0±1.5 vs. 12.1±1.7, n=7). PFC synaptic markers (synaptophysin, PSD-95 and gephyrin, SERT, DAT, n=4-6) increased from young adulthood to middle age and declined at 21M (P<0.05) while in HIPP and STR a progressive decline was observed. MNT enhanced more effectively RAM performance in middle-aged rats than in juvenile and young adults (P<0.05, n=5-8).
Altered monoaminergic transmission in the HIPP, PFC and STR likely contributes to age-related cognitive decline and impaired MN responses. Cognitive stimulation involving MN paradigms may constitute a valuable principle to rescue cognitive decline in the elderly and deserves further investigation.
1. Aidil-Carvalho (2024) J Neurosci Res 102:e25333; 2. Nascimento (2024) Biomedicines 12:631.