Scholarlink

<p>Bisphenol S (BPS), a widely used substitute for bisphenol A (BPA), is increasingly detected in consumer products and aquatic environments, yet its neurotoxic potential remains insufficiently understood. Building on our previous findings that BPS induces anxiety-like behaviour and oxidative damage in zebrafish, the present study investigates the mechanistic basis of BPS-mediated neurotoxicity with a focus on stress-activated kinase signalling, antioxidant defences, and neurotrophic regulation. Adult zebrafish were exposed to a sub-lethal concentration of BPS (63.93 µM) for 7, 14, and 21 days, followed by neurobehavioral, biochemical, molecular, and histological analyses. Chronic BPS exposure resulted in pronounced anxiety-like behaviour and deficits in recognition memory, as evidenced by performance impairments in the novel tank diving test and novel object recognition test. These behavioural alterations coincided with elevated oxidative stress, including increased lipid peroxidation and protein carbonylation, alongside a progressive decline in superoxide dismutase activity. BPS also caused a significant, time-dependent rise in intracellular calcium levels, suggesting disrupted cellular homeostasis. Neuromorphological assessment revealed marked neuronal loss and pyknosis in the periventricular grey zone of the optic tectum, consistent with oxidative and excitotoxic damage. At the molecular level, western blot analysis showed robust activation of the c-Jun N-terminal kinase (JNK) pathway, evidenced by elevated phosphorylated c-Jun, accompanied by a substantial reduction in Nrf2 expression, indicating suppressed antioxidant defence capacity. In parallel, expression of brain-derived neurotrophic factor (BDNF) was significantly decreased following prolonged exposure, pointing to impaired neurotrophic support and synaptic plasticity. Together, these findings demonstrate that BPS induces neurobehavioral disturbances through a multifaceted mechanism involving oxidative stress, calcium dysregulation, activation of pro-apoptotic JNK signalling, suppression of Nrf2-mediated antioxidant activity, and inhibition of BDNF expression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Bisphenol S–Induced Neurobehavioral Impairment Is Characterized by c-Jun Activation and Distinct Dysregulation of Nrf2 and BDNF in the Zebrafish Brain

  • 期刊论文

  • 发表日期：

    2026年7月11日

查看全文
  • Bhabani Sankar Sahoo,
  • Prerana Sarangi,
  • Pradyumna Kumar Sahoo,
  • Suvam Bhoi,
  • Lilesh Kumar Pradhan,
  • Saroj Kumar Das

摘要

Bisphenol S (BPS), a widely used substitute for bisphenol A (BPA), is increasingly detected in consumer products and aquatic environments, yet its neurotoxic potential remains insufficiently understood. Building on our previous findings that BPS induces anxiety-like behaviour and oxidative damage in zebrafish, the present study investigates the mechanistic basis of BPS-mediated neurotoxicity with a focus on stress-activated kinase signalling, antioxidant defences, and neurotrophic regulation. Adult zebrafish were exposed to a sub-lethal concentration of BPS (63.93 µM) for 7, 14, and 21 days, followed by neurobehavioral, biochemical, molecular, and histological analyses. Chronic BPS exposure resulted in pronounced anxiety-like behaviour and deficits in recognition memory, as evidenced by performance impairments in the novel tank diving test and novel object recognition test. These behavioural alterations coincided with elevated oxidative stress, including increased lipid peroxidation and protein carbonylation, alongside a progressive decline in superoxide dismutase activity. BPS also caused a significant, time-dependent rise in intracellular calcium levels, suggesting disrupted cellular homeostasis. Neuromorphological assessment revealed marked neuronal loss and pyknosis in the periventricular grey zone of the optic tectum, consistent with oxidative and excitotoxic damage. At the molecular level, western blot analysis showed robust activation of the c-Jun N-terminal kinase (JNK) pathway, evidenced by elevated phosphorylated c-Jun, accompanied by a substantial reduction in Nrf2 expression, indicating suppressed antioxidant defence capacity. In parallel, expression of brain-derived neurotrophic factor (BDNF) was significantly decreased following prolonged exposure, pointing to impaired neurotrophic support and synaptic plasticity. Together, these findings demonstrate that BPS induces neurobehavioral disturbances through a multifaceted mechanism involving oxidative stress, calcium dysregulation, activation of pro-apoptotic JNK signalling, suppression of Nrf2-mediated antioxidant activity, and inhibition of BDNF expression.