Sex‐specific effect of prenatal alcohol exposure on N‐methyl‐D‐aspartate receptor function in orbitofrontal cortex pyramidal neurons of mice. (29th September 2021)

• Record Type: Journal Article
• Authors: Licheri, Valentina; Chandrasekaran, Jayapriya; Bird, Clark W.; Valenzuela, C. Fernando; Brigman, Jonathan L.
• Is Part Of: Alcoholism. Volume 45:Number 10(2021)
• Page Start: 1994
• Page End: 2005
• Publication Date: 2021-09-29
• Subjects: linear mixed model -- NMDA receptor subunits -- OFC -- prenatal alcohol exposure -- pyramidal neurons -- synaptic fraction; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.14697
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract: Background: Alcohol consumption during pregnancy can produce behavioral and cognitive deficits that persist into adulthood. These include impairments in executive functions, learning, planning, and cognitive flexibility. We have previously shown that moderate prenatal alcohol exposure (PAE) significantly impairs reversal learning, a measure of flexibility mediated across species by different brain areas that include the orbital frontal cortex (OFC). Reversal learning is likewise impaired by genetic or pharmacological inactivation of GluN2B subunit‐containing N‐methyl‐D‐aspartate receptors (NMDARs). In the current study, we tested the hypothesis that moderate PAE persistently alters the number and function of GluN2B subunit‐containing NMDARs in OFC pyramidal neurons of adult mice. Methods: We used a rodent model of fetal alcohol spectrum disorders and left offspring undisturbed until adulthood. Using whole‐cell, patch‐clamp recordings, we assessed NMDAR function in slices from 90‐ to 100‐day‐old male and female PAE and control mice. Pharmacologically isolated NMDA receptor‐mediated evoked excitatory postsynaptic currents (NMDA‐eEPSCs) were recorded in the absence and presence of the GluN2B antagonist, Ro25‐6981(1 µM). In a subset of littermates, we evaluated the level of GluN2B protein expression in the synaptic fraction using Western blotting technique. Results: Our results indicate that PAE females show significantly larger (~23%) NMDA‐eEPSC amplitudes than controls, while PAE induced a significant decrease (~17%) in NMDA‐eEPSC current density of pyramidal neurons recorded in slices from male mice. NMDA‐eEPSC decay time was not affected in PAE‐exposed mice from either sex. The contribution of GluN2B subunit‐containing NMDARs to the eEPSCs was not significantly altered by PAE. Moreover, there were no significant changes in protein expression in the synaptic fraction of either PAE males or females. Conclusions: These findings suggest that low‐to‐moderate PAE modulates NMDAR function in pyramidal neurons in a sex‐specific manner, although we did not find evidence that the effect is mediated by dysfunction of synaptic GluN2B subunit‐containing NMDARs. Abstract : Prenatal alcohol exposure (PAE) induces long lasting behavioral and cognitive impairments collectively known as Fetal Alcohol Spectrum Disorder (FASD). Unfortunately the molecular mechanisms are still not understood. In the present study the function and expression of N‐Methyl‐D‐Aspartate receptors (NMDARs) expressed in pyramidal neurons of orbital frontal cortex (OFC) was assessed. Results show that PAE modulates the NMDA currents in sex‐specific manner, but without affecting the function and expression of GluN2B‐containing NMDAR.