Project description:Numerous neurological disorders, including Alzheimer's disease, display a sex-biased prevalence. To identify molecular correlates of this sex bias, we investigated sex-differences in molecular pathology in the hippocampus using the 5XFAD mouse model of Alzheimer's disease during early stages of disease progression (1, 2, and 4 months of age).
Project description:A variety of neurological disorders, including Alzheimer’s disease, Parkinson’s disease, major depressive disorder, dyslexia and autism, are differentially prevalent between females and males. To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we measured both mRNA and protein in the hippocampus of female and male mice at 1, 2, and 4 months of age with RNA-sequencing and mass-spectrometry respectively. Differential expression analyses identify 2699 genes that are differentially expressed between animals of different ages. 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation across all ages, 8 of which are heat-shock proteins. We also find a modest correlation between levels of mRNA and protein in the mouse hippocampus (Rho = 0.53). This study adds to the substantial body of evidence for transcriptomic regulation in the hippocampus during postnatal development. Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus.
Project description:Like many neurological disorders, Alzheimer’s disease has a sex-biased epidemiological profile, affecting approximately twice as many women as men. The cause of this sex difference has yet to be elucidated. To identify molecular correlates of this sex bias, we investigated molecular pathology in females and males using the 5XFAD genetic mouse model of Alzheimer’s disease. We profiled the transcriptome and proteome of the mouse hippocampus during early stages of disease development (1, 2, and 4 months) with RNA-sequencing and Liquid-chromatography mass spectrometry.
Project description:This project examined sex differences in the role of degradation-specific protein polyubiquitination in the hippocampus during context fear memory formation in male and female rats.
Project description:Long-term memory formation is dependent on gene expression changes in the hippocampal region of the brain. Aging-related memory impairments and incidence of pathological memory disorders such as Alzheimer’s disease differ between males and females, and yet little is known about how aging-related changes to the transcriptome and chromatin environment differs between sexes in the hippocampus. To investigate this question, we compared the chromatin accessibility landscape and gene expression/alternative splicing pattern of young adult and aged mouse hippocampus of both males and females using ATAC-seq and RNA-seq. We detected significant aging-dependent changes in the expression of genes involved in immune response, cell adhesion, and synaptic function, and aging-dependent changes in the alternative splicing of myelin sheath genes. We found significant sex-bias in the expression and alternative splicing of hundreds of genes, including aging-dependent female-biased expression of myelin sheath genes and aging-dependent male-biased expression of genes involved in synaptic activity. Aging was associated with increased chromatin accessibility in both male and female hippocampus, especially in repetitive elements, and with an increase in LINE1 transcription. We detected significant sex-bias in chromatin accessibility in both autosomes and the X chromosome, with male-biased accessibility enriched at promoters and CpG-rich regions. Overall, sex differences in both gene expression and chromatin accessibility were amplified with aging, revealing that although some aspects of hippocampal aging are sex-independent, underlying sex differences in gene expression and chromatin dynamics in aging may shed light on sex differences in aging-related and pathological memory loss.
Project description:Long-term memory formation is dependent on gene expression changes in the hippocampal region of the brain. Aging-related memory impairments and incidence of pathological memory disorders such as Alzheimer’s disease differ between males and females, and yet little is known about how aging-related changes to the transcriptome and chromatin environment differs between sexes in the hippocampus. To investigate this question, we compared the chromatin accessibility landscape and gene expression/alternative splicing pattern of young adult and aged mouse hippocampus of both males and females using ATAC-seq and RNA-seq. We detected significant aging-dependent changes in the expression of genes involved in immune response, cell adhesion, and synaptic function, and aging-dependent changes in the alternative splicing of myelin sheath genes. We found significant sex-bias in the expression and alternative splicing of hundreds of genes, including aging-dependent female-biased expression of myelin sheath genes and aging-dependent male-biased expression of genes involved in synaptic activity. Aging was associated with increased chromatin accessibility in both male and female hippocampus, especially in repetitive elements, and with an increase in LINE1 transcription. We detected significant sex-bias in chromatin accessibility in both autosomes and the X chromosome, with male-biased accessibility enriched at promoters and CpG-rich regions. Overall, sex differences in both gene expression and chromatin accessibility were amplified with aging, revealing that although some aspects of hippocampal aging are sex-independent, underlying sex differences in gene expression and chromatin dynamics in aging may shed light on sex differences in aging-related and pathological memory loss.