Browsing by Subject "hippocampal neurogenesis"

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    Housing in Environmental Complexity Following Wheel Running Augments Survival of Newly-Generated Hippocampal Neurons in a Rat Model of Binge Alcohol Exposure during the Third Trimester Equivalent
    (Wiley, 2012-07) Hamilton, Gillian F.; Boschen, Karen E.; Goodlett, Charles R.; Greenough, William T.; Klintsova, Anna Y.; Department of Psychology, School of Science
    Background Binge-like alcohol exposure in neonatal rats during the brain growth spurt causes deficits in adult neurogenesis in the hippocampal dentate gyrus (DG). Previous data from our lab demonstrated that twelve days of voluntary wheel-running (WR) beginning on postnatal day (PD) 30 significantly increased the number of newly-generated cells evident in the DG on PD42 in both alcohol-exposed and control rats, but 30 days later a sustained beneficial effect of WR was evident only in control rats. This study tested the hypothesis that housing rats in environmental complexity (EC) following WR would promote survival of the newly-generated cells stimulated by WR, particularly in alcohol-exposed rats. Methods On PD4-9, pups were intubated with alcohol in a binge-like manner (5.25g/kg/day), sham-intubated, or reared normally. In Experiment 1, animals were either assigned to WR during PD30-42 or were socially housed (SH). On PD42, animals were injected with bromodeoxyuridine (BrdU; 200mg/kg) and perfused two hours later to confirm the WR-induced stimulation of proliferation. In Experiment 2, all animals received WR on PD30-42 and were injected with BrdU on the last full day of WR. On PD42, animals were randomly assigned either to EC (WR/EC) or SH (WR/SH) for 30 days and subsequently perfused and brains were processed for immunohistochemical staining to identify BrdU+, Ki67+ and BrdU+/NeuN+ labeled cells in DG. Results In Exp. 1, WR exposure significantly increased the number of proliferating cells in all three postnatal conditions. In Exp. 2, the alcohol-exposed rats given WR/SH had significantly fewer BrdU+ cells compared to control rats given WR/SH. However, WR/EC experience significantly increased the number of surviving BrdU+ cells in both the alcohol-exposed and sham-intubated groups compared to WR/SH rats of the same neonatal treatment. Approximately 80% of the surviving BrdU+ cells in the DG across the conditions were co-labeled with NeuN. Conclusions WR followed by EC could provide a behavioral model for developing interventions in humans to ameliorate hippocampal-dependent impairments associated with fetal alcohol spectrum disorders.
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    Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease
    (Office of the Vice Chancellor for Research, 2016-04-08) Horgusluoglu, Emrin; Nho, Kwangsik; Risacher, Shannon L.; Saykin, Andrew J.
    Background: New neurons are generated throughout adulthood in the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into hippocampal networks during maintenance of neural circuits and in turn contribute to learning and memory. Numerous intrinsic and extrinsic factors such as growth factors, transcription factors, and cell cycle regulators control neural stem cells proliferation, differentiation, and maintenance into mature neurons. However, the genetic mechanisms controlling adult hippocampal neurogenesis remain unclear. We performed a gene-based association analysis of neurogenesis pathway-related candidate genes using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Methods: Neurogenesis-related genes were curated from existing databases (Qiagen RT2 Profiler PCR Arrays, GoGene and MANGO). The gene list was filtered by AD susceptibility genes from the Alzgene database (http://www.alzgene.org/) and large-scale GWAS (Lambert,et al. 2013, Nature). Caucasian non-Hispanic individuals (N=1,525) with AD or mild cognitive impairment (MCI) and cognitively normal older adults from the ADNI cohort with MRI and genotyping data were included. Gene-based association analysis of neurogenesis pathway-related candidate genes was performed. Baseline bilateral hippocampus and hippocampal subfield (CA regions and dentate gyrus) volumes were extracted from MRI and served as phenotypes. Gender, age, intracranial volume, MRI field strength, and diagnosis at scanning were entered as covariates. The empirical p value from permutation testing for each gene was adjusted for the number of significant SNPs in each gene. Results: ADORA2A was significantly associated with total hippocampal volume and hippocampal subfield volumes (p<0.001). For the most significant SNP (rs9608282) in ADORA2A, dosage of the minor allele (T) increased hippocampal volume. rs9608282 was also associated with composite memory score (p= 0.0076). Conclusion: ADORA2A-mediated control of neuroinflammation modulates adult neurogenesis and the inhibition of ADORA2A prevents Aβ-induced neurotoxicity. Targeted pathway-based genetic analysis combined with brain imaging endophenotypes appears promising to help elucidate disease pathophysiology and identify potential therapeutic targets. **Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/ uploads/how_to_apply/ADNI_Acknowledgement_List.pdf