Goat milk exerts anxiolytic and anti-depressive effects through modulating JAK/STAT3 and p-Akt/CREB signaling pathways in chronic unpredictable mild stress mice

Anxiety and depression are the second major diseases in the world. Current antidepressants are not universally effective and always cause numerous side effects and strong dependence. Cow milk, as a daily nutritional supplement, can assist in the treatment to improve anxiety and depression symptoms. Whereas, cow milk allergy and lactose intolerance are present in a sizable portion of the population. Compared with cow milk, goat milk has higher nutritional value, easier digestion, lower allergy and better tolerance. However, the anxiolytic and anti-depressive effects of goat milk are still pending, and the related mechanisms are not confirmed. Therefore, in the present study, cow milk as a control, the anxiolytic and anti-depressive effects of goat milk were investigated in chronic unpredictable mild stress mice, and the corresponding mechanism was explored. Our data suggested that goat milk elevated monoamine neurotransmitters, reduced pro-inflammatory cytokines release, increased anti-inflammatory cytokine concentration, inhibited the expression of NSE, STAT3, and NF-κB, and increased the expression of p/Akt and CREB. We concluded that goat milk exerted anxiolytic and anti-depressive effects by increasing neurotransmitters and reducing inflammatory mediators via modulating hippocampal JAK/STAT3 and p-Akt/CREB signaling pathways. No significant difference in the anti-depressive effect between cow and goat milk was observed. This study firstly demonstrates that goat milk has a similar effect as cow milk in improving anxiety and depression symptoms and goat milk might be expected as an ideal nutritional supplement for people suffering from anxiety and depression who are allergic or lactose intolerant to cow milk.