Effects of postnatal alcohol exposure on hippocampal gene expression and learning in adult mice

Abstract

Fetal alcohol syndrome (FAS) is a condition resulting from excessive drinking by pregnant women. Symptoms of FAS include abnormal facial features, stunted growth, intellectual deficits and attentional dysfunction. Many studies have investigated FAS, but its underlying mechanisms remain unknown. This study evaluated the relationship between alcohol exposure during the synaptogenesis period in postnatal mice and subsequent cognitive function in adult mice. We delivered two injections, separated by 2 h, of ethanol (3 g/kg, ethanol/saline, 20% v/v) to ICR mice on postnatal day 7. After 10 weeks, we conducted a behavioral test, sacrificed the animals, harvested brain tissue and analyzed hippocampal gene expression using a microarray. In ethanol-treated mice, there was a reduction in brain size and decreased neuronal cell number in the cortex, and also cognitive impairment. cDNA microarray results indicated that 1,548 genes showed a > 2-fold decrease in expression relative to control, whereas 974 genes showed a > 2-fold increase in expression relative to control. Many of these genes were related to signal transduction, synaptogenesis and cell membrane formation, which are highlighted in our findings.

Effect of Alcohol on Hippocampal-Dependent Plasticity and Behavior: Role of Glutamatergic Synaptic Transmission

“…Aside from that, the mild defect on MWM performance found in adolescent offspring was not observed in adulthood, indicating that alcohol exposure on E8 did not profoundly affect the hippocampal function (Fish et al, 2018). Further, the administration of two hypodermal injections of alcohol at P7 impaired the performance on the MWM in the training and probe trial of 11-week-old mice, which was a session without the platform (Lee et al, 2016). However, a disadvantage of this model in studying the effects of alcohol in brain development is that it is assumed that the placenta and the mother's alcohol metabolism do not have a relationship with the effects of alcohol in the fetus.…”

“…In rodents, the highest velocity occurs postnatally, in contrast to humans where this phenomenon occurs in the third trimester of development (Cudd, 2005). With this consideration, a single injection of alcohol in pregnant rats (E8) did not produce effects on spatial memory in the adult offspring, while a single alcohol injection during the postnatal period on P7 produced effects on spatial memory when measured at P98 (Sadrian et al, 2014), indicating a role of the developmental stage on effects of alcohol on hippocampal function (Lee et al, 2016;Breit et al, 2019). Vapor ethanol exposure in the perinatal period (P1-P8) impaired the performance of 5-month-old litters in a MWM probe trial, correlating with deficiencies in the gene expression of glutamatergic synapse proteins in the hippocampus (Zink et al, 2011).…”

Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice

“…Over 30 of the differentially expressed genes from the NOE, RSE, or RSE vs. NOE group have been reported as involved in alcohol-related behaviors or expression changes in relation to alcohol exposure. For example, multiple genes from all three groups have been found to have altered gene expression in regions such as the hippocampus, nucleus accumbens, amygdala, and ventral tegmental area following exposure to ethanol in animals: Actn1 , Aif1 , Dcx , Errfi1 , Havcr2 , Homer1 , Ifitm3 , Jam2 , Kif15 , Mfsd2 , Mtfmt , Serpinh1 , Synj1 , Thrsp , Tsc22d3 , Zfp451 (McBride et al, 2013, 2014, 2012; Bell et al, 2009; Kimpel et al, 2007; Lee et al, 2015; Piechota et al, 2010; Rodd et al, 2008). Other studies examining differences in alcohol preference and alcohol consumption in animal models identified Cacnalg , Kcnh7 , Fgf12 , Gad1 , Luc7l2 , Smpd3 , and Ttn (Carr et al, 2007; Fehr, Rademacher, & Buck, 2003; McClintick et al, 2013; Mulligan et al, 2008; Wang et al, 2014, p. P12).…”

Narrativa oral de indivíduos com Transtorno do Espectro Alcoólico Fetal

“…In individuals with FASD, there have been frequent reports of deficits in problem-solving abilities, abstraction and elaboration of concepts (4) , executive functions -particularly visuospatial (5) -, verbal and non-verbal working memory deficits (6,7) , variable socio-behavioral impairment (8,9) , and significant impairment in social and language skills that tends to be persistent thoughout life (10) .…”