Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice

BACKGROUND: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric condition affecting 1-3% of the worldwide population. OCD has a strong genetic component, and the SLC1A1 gene that encodes neuronal glutamate transporter EAAT3 is a strong candidate for this disorder. To evaluate the impact of reduced EAAT3 expression in vivo, we studied male EAAT3 heterozygous and wild-type littermate mice using a battery of behavioral paradigms relevant to anxiety (open field test, elevated plus maze) and compulsivity (marble burying), as well as locomotor activity induced by amphetamine. Using high-performance liquid chromatography, we also determined tissue neurotransmitter levels in cortex, striatum and thalamus-brain areas that are relevant to OCD. RESULTS: Compared to wild-type littermates, EAAT3 heterozygous male mice have unaltered baseline anxiety-like, compulsive-like behavior and locomotor activity. Administration of acute amphetamine (5 mg/kg intraperitoneally) increased locomotion with no differences across genotypes. Tissue levels of glutamate, GABA, dopamine and serotonin did not vary between EAAT3 heterozygous and wild-type mice. CONCLUSIONS: Our results indicate that reduced EAAT3 expression does not impact neurotransmitter content in the corticostriatal circuit nor alter anxiety or compulsive-like behaviors.

Changes of neuronal glutamate transporter in the rat hippocampus during acute cerebral ischemia / 中国病理生理杂志

AIM: To investigate the changes of neuronal glutamate transporter (EAAC1) at different ischemic times in the rat hippocampus in early stage. METHODS: Brain microinjection of EAAC1 antisense oligodeoxyneucleotide (EAAC1 antisense) was adopted and focal transient ischemia was produced by the filament method of middle cerebral artery occlusion (MCAO). Western blotting and TTC staining analysis were adopted for observing EAAC1 expression and infarction volume in ischemic region .The expression of EAAC1 mRNA and protein at different ischemic times in the rat ischemic hippocampus was assessed by RT-PCR and Western blotting analysis. RESULTS: Compared with EAAC1 sense group, the volume of brain ischemic infarction [(105.67?8.70) mm~3] was reduced after brain microinjection of EAAC1 antisense. Compared with the sham-operated control, EAAC1 mRNA was significantly higher at 6 h and at (24 h) in the hippocampal regions during ischemia, while protein expression was higher at 24 h only. EAAC1 mRNA and protein expression were unchanged at other ischemic times. CONCLUSION: EAAC1 is associated with ischemic injury and its expression is increased in the hippocampal regions after focal cerebral ischemia.