Behavioral effects of Gabrb2 knockout and an anti-inflammatory herbal formula on aged mice

Aim: We previously observed oxidative stress and neuroinflammation caused behavioral and neurochemical changes in young Gabrb2 (gamma-aminobutyric acid type A receptor β2 subunit) knockout (KO) mice. Aging was moderated in a D-galactose-induced accelerated aging mouse model by an oral Chinese medicinal herbal formula BYPA consisting of Bupleurum chinense, Corydalis yanhusuo, Polygonum multiflorum, and Albizia julibrissin. The present study aimed to examine first whether Gabrb2-KO phenotypes observed in young adult mice would remain in aged mice, and whether BYPA may display a role of anti-aging in naturally aged mice. Methods: A range of behavioral tests were performed on naturally aged Gabrb2-KO and wild-type (WT) mice treated with BYPA. Oxidation stress level was evaluated by MDA (malondialdehyde) test, and the expressions of antioxidant enzymes (superoxide dismutase and catalase) were measured using RT-qPCR (reverse transcription-quantitative polymerase chain reaction). Results: Behavioral tests on aged Gabrb2-KO mice showed hyper-locomotor activity, social function deficit, decreased levels of anxiety and depression, consistent with a previous study on young Gabrb2-KO mice. Oral administration of BYPA ameliorated anxiety, activity, and depression. Remarkably, BYPA protected facial tissues with regrowth of significantly lost hairs and whiskers due to aging. It also reduced oxidative stress levels and enhanced the expression of antioxidant enzymes. Conclusions: The present study showed that schizophrenia-like behavioral changes were exhibited by aged Gabrb2-KO mice, similar to what was reported earlier, suggesting that the observed behavioral changes did not result from any developmental delay, but a direct result of Gabrb2-KO, reconfirming the critical role of Gabrb2 in schizophrenia etiology. Since the BYPA herbal formula moderated the oxidative status and enhanced the expressions of antioxidant enzymes in D-galactose-accelerated aging as well as naturally aged mice, it might furnish a useful health supplement to both the schizophrenic and the aged populations, due to its significant antioxidation and anti-inflammation effects exerted in the brain.