Hippocampal transcriptome profiling in the aged rat brain for the prediction of age-associated cognitive decline
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1
Universiti Kebangsaan Malaysia, Department of Biochemistry, Faculty of Medicine, Malaysia
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2
Universiti Teknologi Mara, Faculty of Medicine, Sungai Buloh Campus, Malaysia
Cognitive decline is present in continuum with advancing of age. To date, the indicator between physiological and pathological cognitive deterioration is still uncertain. This study is aimed to determine the differentially expressed genes in rat hippocampus at different ages and correlate the findings with the cognitive functions that may predispose to the brain ageing process. Cognitive functions were determined through open field, Morris water maze and object recognition test on 3, 14, 18, 23 and 27 months-old Sprague Dawley rats. Upon the completion of cognitive assessment at each age, hippocampus (HC) was carefully dissected and the total RNA was extracted and proceeded with microarray analysis (Affymetrix GeneChip® Rat Gene 2.0 ST Array). Raw signal intensity data was subjected to background subtraction and quantile normalization by Affymetrix® Expression ConsoleTM Software. Analysis of variance (ANOVA), Gene Set Enrichment Analysis (GSEA) and pathway enrichment analysis of normalized probe intensities values were performed using Partek® Genomic Suite® (v6.6). Our data indicated that ageing not only affects the spatial and non-spatial memory but also decreased the exploratory behaviours in our animal model. The levels of anxiety were also higher in the older rats. From the microarray data, a total of 4,619 genes were differentially expressed (p<0.05) in 14, 18, 23, and 27 months-old HC when compared with 3 months old group. Among these genes, 2,384 genes were downregulated and 2,235 genes were upregulated. These genes were enriched, showing that the genes were involved in 22 KEGG pathways with enrichment score more than 3.0 (p<0.05), which include ErbB signaling pathway, synthesis and degradation of ketone bodies, antigen processing and presentation, metabolic pathways and oxidative phosphorylation as well as SNARE interactions. As conclusion, transcriptome profiling in hippocampus could be utilized to gain more comprehensive understanding of brain ageing process and identify potential biomarkers for age-associated cognitive decline.
Acknowledgements
This study was funded by Long term Research Grant Scheme (LRGS/BU/2012/UKM-UKM/K/04) and Fundamental Research Grant Scheme (FRGS/2/2013/SKK01/UKM/03/4) from Ministry of Higher Education Malaysia
Keywords:
Gene Expression,
Hippocampus,
Oxidative Stress,
neurodegeneration,
antioxidant
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Symposium 7: New Insights on Oxidative Stress in Neurodegenerative Diseases and Therapeutic Potential of Anti- Oxidants as a Drug for the Pre-Emptive Medicine
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Damanhuri
HA,
Achin
N,
Makpol
S,
Mazlan
M and
Wan Ngah
W
(2016). Hippocampal transcriptome profiling in the aged rat brain for the prediction of age-associated cognitive decline.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00030
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Received:
26 Jul 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Dr. Hanafi A Damanhuri, Universiti Kebangsaan Malaysia, Department of Biochemistry, Faculty of Medicine, Cheras, Kuala Lumpur, Malaysia, hanafi.damanhuri@ppukm.ukm.edu.my