Effects of heat stress on hippocampal GABAergic and glutamatergic neurochemical balance and its relationship to anxiety-like behavior

Climate change may contribute to anxiety disorders. Heat stress impacts the hippocampal formation, altering the balance between excitatory and inhibitory neurotransmission. Our previous studies showed that heat induces anxiety-like behaviors in mice. The aim was to examine GABAergic and glutamatergic components in the hippocampal formation underlying heat-induced anxiety-like behavior. Adult female mice were exposed to a heat wave (8 h heat/day, 33°C maximum and 28°C minimum) for one week (HS group). Controls (CTL) were maintained at 21±1°C. On the last day, mice were also classified as Estrus or Diestrus (N=4/group). GABA-A, Parvalbumin, Calretinin, NMDAR1, and AMPA expression were analyzed by IHC, and optical density (OD) was quantified. GABA-A and Calretinin OD significantly increased (p<0.05) in CTL Estrus vs. the other groups, while heat exposure suppressed estrous cycle-dependent fluctuations. Parvalbumin interneuron number significantly decreased (p<0.05) during estrus regardless of treatment. NMDAR1 OD increased significantly (p<0.05) in CTL Diestrus vs. the other groups, while heat exposure prevented estrous cycle-dependent fluctuations. AMPA OD significantly (p<0.05) decreased in the stratum pyramidale and lacunosum-moleculare at Diestrus compared to Estrus. These findings suggest that heat stress disrupts the neurochemical balance of the hippocampal formation in a reproductive hormone-dependent manner, potentially contributing to heat-induced anxiety-like behavior.