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Year : 2017  |  Volume : 2  |  Issue : 2  |  Page : 60-66

Postsynaptic density-95 expression is increased following neonatal ethanol exposure in wild-type but not adenylyl cyclase 1 and 8 knockout mice

John D. Dingell VA Medical Center; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA

Correspondence Address:
Alana C Conti
John D. Dingell VA Medical Center, B4250 (11R), 4646 John R St., Detroit, MI 48201
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ed.ed_26_16

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Context: Fetal alcohol spectrum disorders are a continuum of defects including cognitive and behavioral impairments. Ethanol exposure causes increased apoptosis in striatum of wild-type (WT) mice within 4 h of exposure, an effect that is exacerbated in mice lacking adenylyl cyclases 1/8 (double knockout [DKO]). Aims: To further understand the effects of neonatal ethanol exposure on striatal neurons, the current study focused on the acute expression of postsynaptic density-95 (PSD-95) and synaptophysin. Subjects and Methods: WT and DKO mice were treated with a single dose of saline or 2.5 g/kg ethanol at postnatal days 5–7. At various time points after ethanol exposure, striatal tissues were collected for protein and mRNA analysis. Statistical Analysis: Independent two-way ANOVAs for each time point were performed using SigmaPlot 12. Results: Genetic deletion of AC1/8 alone significantly increased PSD-95 expression at all time points analyzed compared to saline-treated WT controls. Neonatal ethanol increased PSD-95 protein expression in WT mice 2–6 h after exposure, with no effect in DKO mice. By 24 and 48 h, ethanol exposure had no effect on PSD-95 protein expression in WT mice but resulted in a significant reduction in DKO mice. Neither PSD-95 mRNA nor synaptophysin protein expression was affected by ethanol and/or AC1/8 knockout. Conclusions: Acute ethanol exposure in WT mice elicits a postsynaptic effect which may be designed to combat the detrimental effects of ethanol exposure. The lack of this acute increase in PSD-95 protein expression in DKO mice may reflect the increased striatal neurodegeneration reported in these mice 4 h after neonatal ethanol treatment compared to WT mice, further evidenced by the delayed reduction in PSD-95 levels 24–48 h postexposure.

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