[Role and biochemical mechanism of exogenous mitochondria in alleviating glutamate-induced neuronal damage]

The excessive concentration of glutamate in the brain is closely related to various neurological diseases, including neurodegenerative diseases, neuropsychiatric diseases, and epilepsy. It is a necessary approach to alleviate neuronal excitatory injury by regulating the glutamate concentration and inhibiting glutamate-induced cell death. To investigate whether mitochondrial transplantation could metabolize excessive glutamate, thereby reducing its neuronal excitatory injury, on the basis of previous research of our laboratory, this study used isolated liver mitochondria to reduce the glutamate level and increase the extracellular ATP content through the mitochondrial transplantation therapy, thereby rapidly inhibiting HT22 neuronal damage caused by glutamate. After the mitochondria kept acting on HT22 cells for 5 h, they could still reduce cellular oxidative stress levels, inhibit cell apoptosis, and improve the neuronal metabolic function. In the mouse model with prefrontal cortex injury caused by local injection of glutamate, the transplanted mitochondria repaired neuronal damage and alleviated abnormal symptoms in the open field test. In summary, this study reveals that transplanted mitochondria have pharmacological activity both in vitro and in vivo, providing a new idea for the treatment for neuronal excitatory injury-related diseases.