Postsynaptic density-95 expression is increased following neonatal ethanol exposure in wild-type but not adenylyl cyclase 1 and 8 knockout mice
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 knoc...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2017-01-01
|
| Series: | Environmental Disease |
| Subjects: | |
| Online Access: | http://www.environmentmed.org/article.asp?issn=2468-5690;year=2017;volume=2;issue=2;spage=60;epage=66;aulast=Susick |
| Summary: | 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. |
|---|---|
| ISSN: | 2468-5690 2468-5704 |