Age-related changes in the brain are a key driver of aging in the whole organism, affecting not only physical health but also mental well-being. Identifying the pathogenic mechanisms of age-related neurodegenerative disorders remains one of the most significant challenges in medicine, biochemistry, and physiology. Substantial evidence supports the involvement of the glutamatergic neurotransmitter system in neurodegenerative pathology. The glutamate-glutamine cycle serves as a neuroprotective mechanism, with its enzymes regulating the balance of the neurotransmitter glutamate. In this study, we investigated the activity of astroglial glutamine synthetase in the cerebral cortex, hippocampus, cerebellum, and hypothalamus of 18-month-old male Wistar rats in models of Alzheimer-type neurodegeneration induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) and glutamate. According to the study design, the rats were divided into four groups (n = 10 per group): 1) intact rats; 2) sham-operated control rats; 3) STZ-ICV rats; and 4) Glu-ICV rats. The results showed that sham-operated control rats demonstrated insignificant impairments in glutamine synthetase activity related to the surgical intervention. The reduced enzyme activity observed in STZ-ICV rats was attributed to STZ-induced brain insulin resistance and Alzheimer-like metabolic disturbances, which may lead to oxidative modification of the enzyme protein and subsequent activity decline. Conversely, the increased glutamine synthetase activity in Glu-ICV rats was likely a response to glutamate, triggering activation of the glutamate-glutamine cycle to remove excess glutamate and maintain its balance. Understanding the biochemical processes underlying glutamate metabolism disorders and related neurodegenerative mechanisms is crucial for developing novel diagnostic and therapeutic strategies for these diseases.
V. R. Khairova (Mon,) studied this question.