Cholinergic regulation of memory retrieval: scopolamine reduces hippocampal neurotrophic and metabolic support

BACKGROUND: Impairment of cholinergic neurotransmission is a defining neurochemical feature of Alzheimer's disease and is closely associated with altered synaptic function and cerebral energy metabolism. Although acetylcholine influences multiple stages of memory processing, the biological substrates supporting the expression of previously acquired recognition memory remain insufficiently characterized. OBJECTIVE: This study examined whether acute antagonism of muscarinic acetylcholine receptors during the test phase of the novel object recognition (NOR) task alters retrieval performance and whether such behavioral effects are accompanied by changes in hippocampal brain-derived neurotrophic factor (BDNF) and glucose transporter-1 (GLUT-1). METHODS: Adult male SWR/J mice underwent NOR training and received intraperitoneal scopolamine (1 mg/kg) or saline 30 min before the test session. Recognition performance was quantified using discrimination index and object exploration measures. Hippocampal tissue was collected immediately after testing for Western blot analysis of BDNF and GLUT-1 expression. RESULTS: Muscarinic receptor blockade significantly reduced the ability of mice to preferentially explore the novel object, while total exploration time was increased versus controls. This behavioral deficit coincided with a decrease in hippocampal pro-brain-derived neurotrophic factor (pro-BDNF) and GLUT-1 protein levels. CONCLUSIONS: These data indicate that cholinergic modulation during recognition memory expression is associated with coordinated neurotrophic and metabolic alterations in the hippocampus. Effective retrieval depends on the integrity of molecular systems supporting plasticity and energy supply, and cholinergic dysfunction may compromise memory expression partly through reducing hippocampal pro-BDNF, providing a mechanistic framework relevant to early cognitive dysfunction in neurodegenerative disease.