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Abstract The aim of the present investigation was to study and compare the possible prophylactic and therapeutic effect of astaxanthin on some aspects of brain cognitive function & hippocampal DNA in rats exposed to chronic unpredictable mild stress. For this purpose; 84 adult male albino rats divided into four equal groups, 21 rats each, were used: non-stressed (NS), stressed non-treated (SNT), stressed astaxanthin pretreated (S+Ast pre) and stressed astaxanthin post treated (S+Ast post). At the end of experimental period (3 weeks); systolic blood pressure was measured for each rat by using rat tail sphygmomanometer technique. Then each group was randomly divided into three subgroups, 7 per cage, for measuring different aspects of brain cognitive abilities: 1- Subgroup – a: for measuring spatial reference memory and learning using Morris water maze test. 2- Subgroup – b: for measuring non spatial memory using Novel object recognition test. 3- Subgroup – c: for measuring spatial working (short term) memory using Y maze spontaneous alternation test. At the next morning, fasting retro-orbital blood samples were collected from all groups and were used for estimation of glycemic state (fasting blood glucose, HbA1c, serum insulin and HOMA IR was calculated), serum corticosterone level and lipid profile (total cholesterol, triglycerides, HDLc and LDLc). Then, rats were sacrificed by cervical elongation and dislocation and skulls were opened and brains were extracted to isolate the hippocampus. Tissues of left hippocampus was hemoginized and was used for measuring total antioxidant capacity (TAC), malondialdehyde level (MDA), tumor necrosis factor alpha (TNF-α), norepinephrine, dopamine, serotonin and brain derived neurotropic factor (BDNF). Tissues of right hippocampus was excised and preserved at -80 degree for DNA and RNA extraction and studying the electophoretic pattern of both hippocampal nucleic acids. In the present investigation, it was found that non spatial memory (represented by discrimination index (d2) and recognition or preference index, (d3) of novel object recognition test), spatial working (short term) memory (represented by spontaneous alternation % of Y maze test), were significantly lower in stressed non-treated (SNT) group when compared to the corresponding values of non-stressed (NS) group, while escape latency of MWM test ( representing decline in spatial reference memory), was significantly higher. This was combined with significant DNA changes (apoptosis pattern) and increased RNA in hippocampus of stressed nontreated (SNT) group when compared to the corresponding values of nonstressed (NS) group. |