The Correlation Between Arc Gene And Memory Ability Formation Of Adolescent Rats And Adult Rats

The molecular basis of learning and memory is the modified synapses togenerate electrical activity of the brain, and that synaptic plasticity. Memoryformation is divided into two phases, the formation of short-term memory is throughmodification of existing proteins to change synaptic plasticity. The formation oflong-term memory need new gene transcription and the production of protein tostabilize these changes. Neurons used several forms to change synaptic strength,making specific synaptic activity enhanced in long-term potentiation (LTP), inlong-term depression (LTD) specific synaptic activity weakened.The study reported that immediate early gene (Immediate-early genes, IEGs)participation in learning and memory-related synaptic plasticity changes, moreresearch is c-fos and Egr1gene, while Arc is special needs in long-term memoryformation and affect all of form of these synaptic plasticity. Arc neurons expressglutamate in the brain to adapt to behavior and learning enhanced synaptic activity,the positioning of the transcription and protein synthesis is tightly regulated, and inthe dendrites, the postsynaptic intensive areas and the nuclear is highly expressed.The study found that the hippocampus is the area to deal with long-term learningand remember sound and light, taste and other events (declarative memory). Thehippocampus can not only make memory, also store memory. Because thehippocampus impaired memory deficit disorder that can lead to memory loss, and inturn, patients lose the ability to imagine the future. McIntyre C et al injected Arcantagonist AOD into rat hippocampus, can block the fast expression of its mRNA orprotein after high-frequency stimulation, break LTP maintenance, and can notconsolidate long-term memory. The mice that knockout Arc mRNA showed memoryimpairment, and can not form memories to a long time space, the fear and the sense oftaste. That Arc regulating the late stage of LTP has an important role in themaintenance of LTP. After the activation of the hippocampal neurons, Arc mRNAcan be transported to dendrites within30min, and accumulate and translate in the site ofthe synaptic activity. Memory is undoubtedly influenced by aging and disease, theresearch reported in the aging hippocampus the levels of Arc gene transcription and proteinexpressiondecline, but thecorrelationofArc in the juvenile stageand memoryabilitywas noreported. This article intends to explore the correlation of the hippocampal Arc and rats’memory capacity in different developmental stages, in order to explore the molecularmechanisms whichdiseasecausessynapticplasticitydysfunction.DNA methylation need in CG-rich gene regulatory regions or in specific CGsites to add methyl. These CpG sites or "islands" are usually in the promoter regions ofmammaliangenes ornear, about40%ofthe genecontainsaCpG island. DNAmethylationhasbeen studied inthe development field extensively, and has been thought this is a static process.However,recent studiesshowthattheDNAmethylationofthe maturecentralnervoussystemisstill an active process, and may through the learning and memory processing quickly anddynamicallyto be adjusted. Interfering withthis process canundermine the long-term memoryconsolidation.Thepresent studywastoinvestigatewhetherDNAmethylationofArcgenehaveinfluenceonArctranscriptionalandmemoryformation.Main results：1. Morris maze was applied to detect place navigation test of2month young ratsand6month adult rats, and found that average escape latency of young rats and adultmice gradually reduced, the third days was significantly lower than the first day (p<0.05), especially in young mice, it showed that learning and memory abilities ofyoung rats is fine, but the average escape latency is still higher than adult rats,although it had no significance, memory capacity is close to adult mice, just unstable.As the increasing times of entering into the water in place navigation test, the escapelatency of young rats shortened (P=0.02to0.001), While it’s different from adult rats,as the increasing times in same day of entering into the water in place navigation test,the escape latency of adult rats shortened, especially comparing the latest2times withthe first time, the difference was significant (P=0.03to0.01). But the second day, theescape latent periods is related to not only times entering into the water, but also thedistance from the point into the water to the platform area, the distance is longer, theescape latency is relatively longer (P=0.03～0.01). To the third day, adult rats formeda stable memory, it isn’t any longer related to times entering into the water and thedistance from the point entering into the water to the platform area. The times of young rats crossing the platform were more than adult rats, the duration in the targetquadrant were longer than adult rats, although the difference was not significant, itcould show that their space exploration abilities were lower than adult rats, furtherillustrating the memory ability was closed to adult rats.2. The results of RT-PCR showed that in the resting Arc mRNA expression inyoung rat and adult rat hippocampus had no significant difference；After positioningnavigation training, Arc mRNA expression in hippocampal in training adult rat wassignificantly higher than the control group（P=0.004to0.001），and is higher than intraining young rat.3, The results of immunohistochemistryto detect hippocampus of young rats and adultrats showed that after Morris maze test, Arc expression levels of behavioraltraining rats washigher than untrained of the control, and Arc expression levels of adult trained rats werehigherthanyoung. ItindicatesthattheArcisrelatedtoratspatialcognitionand age.4, FISH test found in positioning navigation training group, Arc mRNAexpression in hippocampus was significantly higher than that in the control group, andalso higher than the young rats.5, RT-PCR and FISH results showed that mRNA expression of Alpha-CaMK2a,ERK1, ERK2, NMDAR2A was no significant difference in hippocampus expressionbetween young rats and adult rats. After positioning navigation training, they inhippocampus were significantly higher than that in the control group, and adult rats ishigher than young rats. It indicates Arc interact the above factors, constitute a signaltransduction pathway, and complete synaptic activity.6, MS-PCR test and sequence analysis showed that, comparing with young ratsin normal control group, young rats and adult rats in positioning navigation trainingArc promoter points8and24had no methylation, but the adult rats in positioningnavigation training group compared with that in normal control group, there was nodiversification in methylation sites. This may explain why Arc expression levels inpositioning navigation training adult rats was higher than that in young rats, and DNAofArc gene in young rats and adult rats had no methylation.