Biology subjects

Abdulai-Saiku, S.

Publications and source records attributed to Abdulai-Saiku, S..

3 recordsLinked to original sources

bioRxiv2022

X chromosome factor Kdm6a enhances memory independent of its demethylase function in the aging XY male brain

Males exhibit shorter lifespan and more cognitive deficits in aging human populations. In mammals, the X chromosome is enriched for neural genes and is a major source of biologic sex difference, in part, because males show decreased expression of select X factors. While each sex (XX and XY) harbors one active X due to X chromosome inactivation in females, some genes, such as Kdm6a, transcriptionally escape silencing in females - resulting in lower levels in males. Kdm6a is a known histone demethylase (H3K27me2/3) with multiple functional domains that is linked with synaptic plasticity and cognition. Whether elevating Kdm6a could benefit the aging male brain and whether this requires its demethylase function remains unknown. We used lentiviral-mediated overexpression of the X factor in the hippocampus of aging male mice and tested their cognition and behavior in the Morris water maze. We found that acutely increasing Kdm6a - in a form without demethylase function - selectively improved learning and memory, without altering total activity or anxiety-like measures, in the aging XY brain. Further understanding the demethylase-independent downstream mechanisms of Kdm6a may lead to novel therapies for treating age-induced cognitive deficits in both sexes.

neuroscience↗

bioRxiv2022

The maternal X chromosome impairs cognition and accelerates brain aging through epigenetic modulation in female mice

Female mammalian cells harbor two X chromosomes, one of maternal and one of paternal origin. During development, one X randomly inactivates1-4. This renders either the maternal or paternal X active, causing X mosaicism that varies among individual females, with some showing considerable or complete skew in the general female population5-7. Parent-of-X-origin can modify epigenetics via DNA methylation8, 9 and possibly gene expression; thus, mosaicism could buffer dysregulated processes in aging and disease. However, whether X skewing - or its mosaicism - alters functions in females is largely unknown. Here we tested whether skew toward the maternal X (Xm) influences key functions of the body. Among cardiac, bone, metabolic, and brain functions, Xm selectively impaired cognition in female mice throughout the lifespan. Cognitive deficits were accompanied by Xm-mediated acceleration of biologic or epigenetic aging of the female hippocampus, a key center for learning and memory. Xm showed epigenetic imprinting of several genes within hippocampal neurons, suggesting silenced cognitive loci. Thus, the maternal X chromosome impaired cognition, accelerated brain aging, and silenced genes. Understanding how the maternal X impairs brain function could lead to new understanding of female heterogeneity in cognitive heath and to X chromosome-derived pathways against cognitive deficits and brain aging.

neuroscience↗

bioRxiv2021

Presence of Toxoplasma gondii tissue cysts in human semen

Toxoplasma gondii is a widely prevalent protozoan parasite in human populations. This parasite is thought to be primarily transmitted through undercooked meat and contamination by cat feces. Here, we demonstrate that Toxoplasma gondii cysts can be found within human semen, thus suggesting a potential for sexual transmission. We visualized Toxoplasma gondii cysts in ejaculates of immune-competent and latently infected human volunteers. We confirmed the encystment by probing transcription of a bradyzoite-specific gene in these structures. These observations extend previous observations of the parasite in semen of several non-human host species, including rats, dogs, and sheep. Toxoplasma gondii infection is a clinically significant infection, in view of its high prevalence, its purported role in neuropsychiatric disorders such as schizophrenia, as well as in the more serious form of congenital toxoplasmosis. Our demonstration of intact Toxoplasma gondii cysts in the ejaculate supports the possibility of sexual transmission of the parasite and provides an impetus for further investigations. ImportanceToxoplasma gondii is recognized as one of the five infections that can harm fetal health. There is also emerging evidence that toxoplasmosis is related to the development of neuropsychiatric disorders. In this context, the current report includes visual evidence of Toxoplasma gondii cyst presence in the semen of human males. It is thus plausible that this clinically significant infection can be sexually transmitted. The existence of sexual transmission in a population, and its relative importance vis-a-vis other transmission routes, remains undetermined. These possibilities are of acute relevance to human health in the context of sexual health and pregnancy management.

microbiology↗