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Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes.

ABSTRACT: Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases for male and female MDD. We evaluated over 160,000 nuclei from 71 female and male donors, leveraging new and pre-existing single-nucleus RNA-sequencing data from the dorsolateral prefrontal cortex. Cell type specific transcriptome-wide threshold-free MDD-associated gene expression patterns were similar between the sexes, but significant differentially expressed genes (DEGs) diverged. Among 7 broad cell types and 41 clusters evaluated, microglia and parvalbumin interneurons contributed the most DEGs in females, while deep layer excitatory neurons, astrocytes, and oligodendrocyte precursors were the major contributors in males. Further, the Mic1 cluster with 38% of female DEGs and the ExN10_L46 cluster with 53% of male DEGs, stood out in the meta-analysis of both sexes.

SUBMITTER: Maitra M

PROVIDER: S-EPMC10203145 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes.

Maitra Malosree M Mitsuhashi Haruka H Rahimian Reza R Chawla Anjali A Yang Jennie J Fiori Laura M LM Davoli Maria Antonietta MA Perlman Kelly K Aouabed Zahia Z Mash Deborah C DC Suderman Matthew M Mechawar Naguib N Turecki Gustavo G Nagy Corina C

Nature communications 20230522 1

Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases for male and female MDD. We evaluated over 160,000 nuclei from 71 female and male donors, leveraging new and pre-existing single-nucleus RNA-sequencing data from the dorsolateral prefrontal cortex. C ...[more]

PMID: 37217515

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Project description:Background The study of behavioral and physiological traits in mosquitoes has been mainly focused on females since males are not hematophagous and thus do not transfer the parasites that cause diseases in human populations. However, the performance of male mosquitoes is key for the expansion of populations and the perpetuation of mosquito species. Pre-copulatory communication between males and females is the initial and essential step for the success of copulation and studying the male facet of this interaction provides fertile ground for the improvement of vector control strategies. Like in most animals, reproduction, feeding, and oviposition are closely associated with locomotor activity in mosquitoes. Rhythmic cycles of locomotor activity have been previously described in Aedes aegypti, and in females, they are known to be altered by blood-feeding and arbovirus infection. In previous work, we found that males in the presence of females significantly change their locomotor activity profiles, with a shift in the phase of the activity peak. Here, we investigated whether this shift is associated with changes in the expression level of three central circadian clock genes. Methods Real-time PCR reactions were performed for the gene period, cycle, and cryptochrome 2 in samples of heads, antennae, and abdominal tips of solitary males and males in the presence of females. Assays with antennae-ablated males were also performed, asking whether this is an essential organ mediating the communication and the variation in activity profiles. Results The gene period showed a conserved expression pattern in all tissues and conditions, while the other two genes varied according to the male condition. A remarking pattern was observed in cry2, where the difference between the amplitude of expression at the beginning of photophase and the expression peak in the scotophase was greater when males were in the presence of females. Antennae ablation in males did not have a significant effect on the expression profiles, suggesting that female recognition may involve other senses besides hearing and olfaction. Conclusion Our results suggest that the expression of gene cryptochrome 2 varies in association with the interaction between males and females. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13071-022-05529-8.

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Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes.

Publications

Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes.

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