One of the trigger mechanisms for the development of neurodegeneration is glutamate excitotoxicity. The ATP-dependent enzyme glutamine synthetase, localized in astrocytes, regulates glutamate homeostasis by catalyzing the synthesis of glutamine from glutamate and ammonia. The purpose of the study was to identify age- and sex-specific changes in glutamine synthetase activity in a streptozotocin-induced model of Alzheimer-type neurodegeneration. The experiments were carried out on 60 old (at the age of 24 months) Wistar rats of both sexes, divided into groups: 1) control (intact) rats; 2) sham-operated rats; 3) rats with intraventricular injection of streptozotocin. using intraventricular injection of streptozotocin. In males, enzymatic activity decreased in the cortex, cerebellum, hippocampus, and hypothalamus by 40%, 33%, 36%, and 26%, respectively, compared with control rats. In females, the decrease was more pronounced, which amounted to 47% in the cortex, 39% in the cerebellum, 43% in the hippocampus, and 32% in the hypothalamus. Thus, the decrease in glutamine synthetase activity is due to age-dependent impairment of glutamate neurotransmission, reduced compensatory capabilities of neurons and altered hormonal status.