Date Published: April 19, 2017
Publisher: John Wiley and Sons Inc.
Author(s): Fan Hu, Tingting Li, Huarui Gong, Zhi Chen, Yan Jin, Guangwei Xu, Ming Wang.
Bisphenol A (BPA), an environmental xenoestrogen, has been reported to induce learning and memory impairments in rodent animals. However, effects of BPA exposure on synaptic plasticity and the underlying physiological mechanisms remain elusive. Our behavioral and electrophysiological analyses show that BPA obviously perturbs hippocampal spatial memory of juvenile Sprague–Dawley rats after four weeks exposure, with significantly impaired long‐term potentiation (LTP) in the hippocampus. These effects involve decreased spine density of pyramidal neurons, especially the apical dendritic spine. Further presynaptic findings show an overt inhibition of pulse‐paired facilitation during electrophysiological recording, which suggest the decrease of presynaptic transmitter release and is consistent with reduced production of presynaptic glutamate after BPA exposure. Meanwhile, LTP‐related glutamate receptors, NMDA receptor 2A (NR2A) and AMPA receptor 1 (GluR1), are significantly downregulated in BPA‐exposed rats. Excitatory postsynaptic currents (EPSCs) results also show that EPSCNMDA, but not EPSCAMPA, is declined by 40% compared to the baseline in BPA‐perfused brain slices. Taken together, these findings reveal that juvenile BPA exposure has negative effects on synaptic plasticity, which result from decreases in dendritic spine density and excitatory synaptic transmission. Importantly, this study also provides new insights into the dynamics of BPA‐induced memory deterioration during the whole life of rats.
Bisphenol A (BPA) is a synthetic compound widely used in producing plastics and epoxy resins. Every year, there is more than 6 billion pounds demanding of BPA for producing dental sealants, thermal receipts, food packaging, plastics bottles, and so on.1 It has been found a broad distribution of BPA in environmental milieus including food, water, dust, and soil.2 A large body of evidence reveals that BPA exposure is related to adverse health effects, e.g., low‐birth weight, reproductive problem, obesity, diabetes, cardiovascular diseases, and cancers.3
Combining behavioral assays and in vivo electrophysiology, the present study is the first to demonstrate that BPA exposure in juvenile rats deteriorated spatial memory and synaptic plasticity in the hippocampal CA1 areas. This involved the decrease of spine density on the dendrites of pyramidal neurons, especially the apical dendrite. Meanwhile, altered synaptic transmission also contributed to BPA‐induced cognitive impairment, with the decrease of presynaptic glutamate synthesis and release, and excitatory receptors expression.
Experimental animals and treatment: Sprague–Dawley rats were obtained from Beijing Experimental Animal Center, P. R. China. All animal experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The study was approved by the Institutional Animal Care and Use Committee of University of Science and Technology of China, P. R. China. Chronic BPA exposure was performed as previously described.35 Male rats were orally treated with or without BPA (1 mg kg−1 d−1, Sigma #239658, dissolved in dimethyl sulfoxide (DMSO)) from postnatal 21–24 to 49–52 d. In this study, one male rat pup per litter from different normal dams, mated with normal adult male SD rats, was used in the control or BPA‐exposed group (8–10 rats per group). The exposure concentration mentioned above was much lower than the currently accepted lowest observed adverse effect level (50 mg kg−1 d−1). In the control group, rats received equivalent DMSO volume instead of BPA (the highest DMSO volume was less than 0.5 mL).