Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes
NEUROSCIENCE LETTERS
Authors: Iwayama, Y; Hashimoto, K; Nakajima, M; Toyota, T; Yamada, K; Shimizu, E; Itokawa, M; Hoshika, A; Iyo, M; Yoshikawa, T
Abstract
D-Serine is an endogenous coagonist that increases the opening of N-methyl-D-aspartate (NMDA)-type glutamate receptor channels. We previously reported a reduction Of D-serine serum levels in schizophrenia, supporting the disease hypothesis of NMDA receptor-mediated hyponeurotransmission. The serum levels Of D-serine are thought to reflect brain D-serine content. It is important to understand whether there is a direct link between the altered D-serine levels and NMDA receptor expression in vivo or whether these are independent processes. Two polymorphisms are known to regulate the expression of NMDA receptor subunit genes: (GT)(n) (rs3219790) in the promoter region of the NR2A subunit gene (GRIN2A) and -200T > G (rs1019385) in the NR2B gene (GRIN2B). These polymorphisms are also reported to be associated with schizophrenia. Therefore, we examined the correlation between these two polymorphisms and D-serine serum levels in mentally healthy controls, schizophrenics and the combined group. We observed no significant genotype-phenotype correlations in any of the sample groups. However, analyses of larger sample numbers and the detection of additional polymorphisms that affect gene expression are needed before we can conclude that NMDA receptor expression and serum levels Of D-serine, if involved in schizophrenia pathophysiology, are independent and additive events. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
Periconceptional maternal alcohol consumption leads to behavioural changes in adult and aged offspring and alters the expression of hippocampal genes associated with learning and memory and regulators of the epigenome
BEHAVIOURAL BRAIN RESEARCH
Authors: Lucia, D.; Burgess, D.; Cullen, C. L.; Dorey, E. S.; Rawashdeh, O.; Moritz, K. M.
Abstract
Maternal alcohol consumption throughout pregnancy can result in long term behavioural deficits in offspring. However, less is known about the impact of alcohol during the periconceptional period (PC). The aim of this study was to examine the effect of PC ethanol (PC:EtOH) exposure on long term cognitive function; including memory and anxiety. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol;vol) or a control diet from 4 days prior to mating until day 4 of pregnancy. Separate cohorts of animals were tested at 6 months (adult) or 15-18 months of age (aged). Offspring underwent a series of behavioural tests to assess anxiety, spatial and recognition memory. The hippocampus was collected, and mRNA expression of epigenetic modifiers and genes implicated in learning and memory were examined. PC:EtOH exposure resulted in a subtle anxiety like behaviour in adult female offspring with a significant reduction in directed exploring/head dipping behaviour during holeboard testing. In aged male offspring, PC:EtOH exposure resulted in a tendency for increased directed exploring/head dipping behaviour during holeboard testing. No differences between treatments were observed in the elevated plus maze. Aged female offspring exposed to PC:EtOH demonstrated short term spatial memory impairment (P < 0.05). PC:EtOH resulted in an upregulation of hippocampal mRNA expression of bdnf, grin2a and grin2b at 18 months of age along with increased expression of epigenetic modifiers (dnmtl, dnmt3a and hdac2). In conclusion, PC:EtOH can lead to sex specific anxiety-like behaviour and impairments in spatial memory and altered hippocampal gene expression.