Protective effects of gastrodin against bisphenol A-induced dopaminergic dysregulation and cognitive impairment in rats

Gastrodin (GAS) is a potent neuroprotective compound extracted from the traditional Chinese medicinal herb Gastrodia elata Blume. However, its role in mitigating bisphenol A (BPA)-induced dopaminergic dysfunction and cognitive impairment remains insufficiently explored. Many studies have shown that BPA exposure causes neurodegeneration via mechanisms involving dopaminergic system dysfunction, oxidative stress, and neuroinflammation. Therefore, the present study aimed to investigate whether GAS mitigates the effects of BPA-induced cognitive impairment through neuroinflammation in a rat model. Weanling male Wistar rats exposed to BPA (50 µg/kg b.wt. × 30 days, po) were subsequently treated with GAS at two dose levels (30 and 60 mg/kg b.wt., ip × 7 days). After 24 h, neurobehavioral functions (Barnes maze and Y-maze tests), cresyl violet staining, and ultrastructural analysis were performed, demonstrating significant memory deficits and neuronal degeneration in BPA-exposed rats. In contrast, GAS treatment significantly improved memory impairment and reduced neuronal cell death in the prefrontal cortex (PFC). mRNA, protein, and immunohistochemical expression of inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), (Iba-1), glial fibrillary acidic protein (GFAP), and nuclear factor kappa B-p65 (NFκB-p65) were significantly increased in BPA-treated rats, indicating enhanced glial activation and neuroinflammation, whereas GAS effectively attenuated these alterations. Additionally, dopaminergic markers such as tyrosine hydroxylase (TH), dopamine transporter-1/solute carrier family 6 member 3 (DAT-1/SLC6A3), and dopamine receptor D4 (DRD4) were significantly downregulated following BPA exposure and were restored by GAS treatment. Overall, findings suggested that GAS exerts protection against BPA-induced neurotoxicity by suppressing NF-κB-mediated neuroinflammatory response and modulating dopaminergic signaling, thereby improving cognitive and neuronal outcomes in the PFC.