Tyrosol ameliorates depressive-like behavior and hippocampal damage in perimenopausal depression rats by inhibiting oxidative stress and thyroid dysfunction.

Perimenopausal depression (PMD) is a common condition during the female perimenopausal period. Tyrosol represents a promising neuroprotective agent. This study aims to determine if tyrosol alleviate PMD progression. A rat model of PMD was established using bilateral ovariectomy and chronic unpredictable mild stress. Behavioral tests showed that tyrosol alleviated the depressive-like behavior in PMD rats. Tyrosol increased sucrose preference in SPT and residence time in the central region of OFT, and reduced immobility time in FST of PMD rats. Apoptosis of neurons in the hippocampus of PMD rats was inhibited by tyrosol treatment, as evidenced by an increase in the protein expression of Bcl-2 and a decrease in the expression of Bax and cleaved caspase-3 in hippocampal tissue. Tyrosol treatment effectively reduced thyroid-stimulating hormone levels and elevated the levels of free triiodothyronine and free thyroxine in the serum of PMD rats. The levels of ROS and MDA were decreased, and the levels of GPX and SOD were increased in the hippocampal tissue of PMD rats by tyrosol treatment. In addition, tyrosol treatment promoted the levels of brain-derived neurotrophic factor (BDNF) and monoamine neurotransmitters (5-HT, DA, and NA) in the hippocampal tissue. In summary, tyrosol might ameliorate depression-like behavior in PMD rats by inhibiting hippocampal oxidative stress and damage and promoting monoamine neurotransmitter release, and restoration of thyroid function may also be involved.