The impact of early-life exercise on CREB-signaling pathway and hippocampus neuroplasticity in diabetic adult male rats; the study of developmental model

Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise’s influence on adult diabetic rats’ memory and neuroplasticity. Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (<i>BDNF</i>), calmodulin-dependent protein kinase (<i>CAMKII</i>), N-methyl-D-aspartate receptors (<i>NMDAR</i>), and cAMP-response element-binding protein (<i>CREB</i>) by western blotting and reverse transcription–polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study’s conclusion, to assess Interleukin-1β levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1. Post-natal exercise improved spatial memory (<i>p</i> &lt; 0.05) and glucose levels (<i>p</i> &lt; 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression (<i>NMDAR</i> 40%, <i>BDNF</i> 62%, <i>CREB</i> 43%, <i>CAMKII</i> 66%), diabetic rats, by study end, showed increased <i>BDNF, NMDARR, CAMKII, CREB</i> protein/gene expression (<i>p</i> &lt; 0.05) in emerging adulthood for both training groups. Early-life exercise influenced hippocampal <i>BDNF/NMDAR-CAMKII/CREB</i> pathways in a diabetic rat model, highlighting post-natal exercise’s role in neuroplasticity memory enhancement and improved glucose level.