Moderate-intensity intermittent exercise prevents memory deficit, hippocampal neuron loss, and elevated level of Alzheimer's dementia markers in the hippocampus of trimethyltin-induced rats

Abstract

Background: Moderate-intensity intermittent exercise (MIIE) has been proposed as an effective method for preventing Alzheimer's dementia (AD).

Aim: This study aimed to investigate the effects of MIIE on the spatial memory and protein level of AD markers in the hippocampus of trimethyltin (TMT)-induced rat model of hippocampal degeneration.

Methods: Male Sprague Dawley (SD) rats were randomly assigned into four groups: normal control (N), exercise control (E), TMT control (T), and exercise and TMT (ET). Rats of the exercise groups (E and ET) were forced to run on a treadmill for 30 min each day at maximum for 12 weeks. Intraperitoneal injection of 8 mg/kgBW TMT was administered as a single dose, 10 days before the last exercise treatment for the T and ET groups. The spatial memory of rats was examined using Morris water maze (MWM) test after the exercise period. After euthanasia, the hippocampal tissue was dissected out and the level of hippocampal presenilin-1 (PSEN-1) and phosphorylated tau (p-tau) protein were measured using ELISA. The total number of hippocampal pyramidal neurons was estimated using unbiased stereological analysis. Qualitative immunohistochemistry was performed to examine the expression of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in paraffin sections of the hippocampus.

Results: TMT exposure induced memory impairment indicated by the T group having the lowest percentage of time and percentage of path length in the target quadrant compared to other groups. MIIE prevented the memory impairment effect of TMT exposure indicated by the ET group having no significantly different MWM performance compared to the E and N groups. The ET group had significantly lower levels of hippocampal AD markers, p-tau and PSEN-1, as well as significantly higher estimated total number of pyramidal neurons of hippocampal CA1 and CA2-3 regions compared to the T group. Expressions of TNF-α was weak, while the expression of IL-10 was stronger in the ET group compared to the control group. The TMT-induced group exhibited stronger expression of BDNF.

Conclusion: MIIE prevents neuronal loss and impaired spatial memory upon TMT exposure most probably via preventing elevated levels of hippocampal AD markers and neuroinflammation. WC:350.

Keywords: Aging hippocampus; Alzheimer's disease markers; Moderate-intensity intermittent exercise; Spatial memory; Trimethyltin-induced neurodegeneration.