Rongrong Wang,Zhi-Hua Liu,Nanxi Bi,Xiaozhen Gu,Chengqing Huang,Ruiqing Zhou,Haoyu Liu,Hui-Li Wang
Bisphenol A (BPA), a well-known environmental endocrine disruptor, has been implicated in anxiety-like behavior. But the neural mechanism remains elusive. Herein, we found that mice exposed to 0.5 mg/kg/day BPA chronically from postnatal days (PND) 21 to PND 80 exhibited depression- and anxiety-like behavior. Further study showed that medial prefrontal cortex (mPFC), was associated with BPA-induced depression- and anxiety-like behavior, as evidenced by decreased c-fos expression in mPFC of BPA-exposed mice. Both the morphology and function of glutamatergic neurons (also called pyramidal neurons) in mPFC of mice were impaired following BPA exposure, characterized by reduced primary branches, weakened calcium signal, and decreased mEPSC frequency. Importantly, optogenetic activation of the pyramidal neurons in mPFC greatly reversed BPA-induced depression- and anxiety-like behavior in mice. Furthermore, we reported that microglial activation in mPFC of mice may also have a role in BPA-induced depression- and anxiety-like behavior. Taken together, the results indicated that mPFC is the brain region that is greatly damaged by BPA exposure and is associated with BPA-induced depression- and anxiety-like behavior. The study thus provides new insights into BPA-induced neurotoxicity and behavioral changes.
Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity. In an acute hippocampal slice 4-aminopyridine (4-AP) epilepsy model in vitro , NBP decreased the epileptiform activity and miniature excitatory postsynaptic current (mEPSC) amplitude; there was no change in the miniature inhibitory postsynaptic current (mIPSC) amplitude or frequency. This effect suggested changes in excitatory synaptic transmission, which was altered through postsynaptic GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs). These findings showed that NBP suppressed epileptiform activity in these epilepsy models and provided the first detailed electrophysiological analysis of the impact of NBP in epilepsy models, which may be employed in future experimental or clinical therapies for patients with epilepsy.
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