Oxytocin-mediated memory modulation in mice with an experimental model of Alzheimer's disease and chronic zinc acetate intoxication

Aim. To identify changes in cognitive function performance and endogenous oxytocin levels in various brain regions and biological fluids in mice with an experimental model of Alzheimer’s disease, chronic zinc acetate intoxication, and their combined effects. Materials and methods. CD-1 mice (n = 32). Chronic zinc acetate intoxication was modeled by administering Zn(CH3CO2)2 (Zn2+ concentration: 5 mg/L) as drinking water for 3 months; the control group received pure water. Alzheimer’s disease was modeled via intrahippocampal β-amyloid injection; the control group received phosphate-buffered saline. Associative memory was assessed using conditioned freezing testing. Oxytocin levels in brain regions and biological fluids were measured via ELISA. Results. Chronic zinc acetate intoxication and its combined effect with β-amyloid led to increased oxytocin levels in the hippocampus, entorhinal cortex, hypothalamic-pituitary region, and cerebrospinal fluid. β-Amyloid exposure either had no effect on oxytocin levels or caused a decrease (amygdala, blood plasma). Conditioned reflex formation and contextual memory were impaired in all experimental groups. Fear-associated memory in mice with the Alzheimer’s model combined with chronic zinc acetate intoxication did not differ from controls. Exposure to β-amyloid alone worsened fear-associated memory. Oxytocin levels in the amygdala correlated with changes in the mice’s ability to form fear memory. Conclusion. Chronic zinc acetate intoxication and its combination with β-amyloid increase oxytocin levels in nearly all examined brain regions and cerebrospinal fluid, likely as a compensatory response to Zn2+ neurotoxicity. Acute β-amyloid exposure did not cause significant changes. Thus, chronic zinc acetate exposure is the primary factor elevating oxytocin levels in the brain and biofluids. Increased oxytocin levels may contribute to the restoration of cognitive functions.

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