A single day of ethanol exposure during development has persistent effects on bi-directional plasticity, N-methyl-d-aspartate receptor function and ethanol sensitivity

Pre-administration of G9a/GLP inhibitor during synaptogenesis prevents postnatal ethanol-induced LTP deficits and neurobehavioral abnormalities in adult mice

“…In another study, loss of H3K9me2 due to partial ablation of G9a leads to the developmental delay, hypotonia, and cranial abnormalities, which are three of the core features of specific intellectual disability syndrome called Kleefstra syndrome (Balemans, et al, 2014) . Thus, it seems possible that genetically predetermined or environmentally (postnatal ethanol) induced epigenetic changes of the enzymes controlling H3K9 dimethylation (Subbanna, et al, 2014, Subbanna, et al, 2013b) may induce long-lasting learning and memory deficits as found in many postnatal ethanol studies (Izumi, et al, 2005, Sadrian, et al, 2012, Subbanna, et al, 2013a, Wilson, et al, 2011). Although more studies are warranted, in P7 ethanol model, the loss of H3K9me2 was initiated with enhanced G9a expression and dimethylation sensitive degradation of H3K9me2 protein (Subbanna, et al, 2013b) and suggest the G9a function is dependent on the level of expression, context and its H3K9 dimethylation activity.…”

“…The developing brain is so sensitive to ethanol exposure that even a single exposure can produce massive losses of neurons in several brain regions (Ikonomidou, et al, 2000) during the first few postnatal days in neonatal mice (postnatal days 4–10 [P4–10]), a developmental period which corresponds with the third trimester pregnancy in humans (Bayer, et al., 1993). Excessive acute ethanol intoxication in P7 mice prompts neurodegeneration in vital brain regions including the hippocampus and cortex (Ikonomidou, et al, 2000, Sadrian, et al, 2012, Subbanna, et al, 2014, Subbanna, et al., 2013a, Subbanna, et al, 2013b, Wilson, et al, 2011), as well as impairments in LTP (Izumi, et al, 2005, Sadrian, et al, 2012, Subbanna, et al, 2013a, Wilson, et al, 2011) and spatial memory task performance in adult mice (Subbanna, et al, 2013a). Similarly, the local and interregional brain circuitry of the olfacto-hippocampal pathway in adult mice is compromised when P7 mice are exposed to acute ethanol (Sadrian, et al, 2012, Wilson, et al, 2011).…”

Fetal alcohol-induced hyperactivity is reversed by treatment with the PPARα agonist fenofibrate in a rat model

“…Even if the observed attention deficit did not correspond to that seen in ADHD, it was also different to that seen in FASD, in which memory disorders are apparent, because our results showed no alcohol-induced memory disorder. Nevertheless, many studies showing impaired learning and memory in a rodent model of FASD employed a protocol of post-natal alcohol exposition (Goodlett and Johnson 1997;Hunt et al 2009;Izumi et al 2005;Ryan et al 2008;Wagner and Hunt 2006). It has been demonstrated that the period of susceptibility to alcohol-induced memory impairment is between PNDs 7 and 9 (Goodlett and Johnson 1997).…”

Sensitivity of N-Methyl-d-Aspartate Receptor–Mediated Excitatory Postsynaptic Potentials and Synaptic Plasticity to TCN 201 and TCN 213 in Rat Hippocampal Slices

“…Furthermore, ifenprodil insensitivity of NMDAR EPSPs in some circumstances has correlated with LTD failure. We observed this when early postnatal rats are exposed to ethanol (Izumi et al, 2005a) or when the immediate early gene Egr3 is deleted during development (Gallitano-Mendel et al, 2007). These findings suggest that GluN2B-containing NMDARs are susceptible to developmental insults but do not indicate that GluN2A-containing NMDARs are immune to these insults.…”

“…We have also reported that ifenprodil sensitivity of NMDAR EPSPs is markedly dampened when rats are exposed to ethanol during synaptogenesis (Izumi et al, 2005a). This observation suggests impairment of GluN2B-containing NMDARs but does not imply that GluN2A-expressing NMDARs are unaffected.…”