Cell Senescence as a Mediator of Age-Dependent Brain Inflammation

Cellular senescence and inflammation are interconnected causes and consequences of tissue aging. Here, we implemented orthogonal approaches to study their interaction in steady-state mature and aged mouse brain. Using single cell sequencing, we identified a putative senescent microglial population, which increased in abundance with age and was characterized by increased expression of p16 and chemotactic senescence associated secretory phenotype (SASP) factors. Using p16-INK-ATTAC transgenic mice to eliminate p16ink4a-positive senescent cells and mass cytometry, we show that p16ink4a-positive cell targeting reduced the abundance of activated inflammatory cells in the aged female brain. Age-dependent declines in executive cognitive function were improved following transgenic p16ink4a-positive cell targeting, and executive function robustly correlated with inflammatory brain cell composition in females. Collectively, our findings demonstrate fundamental differences in the age- and sex-dependent brain inflammatory landscape and implicate p16ink4a-positive senescent cell targeting as a therapeutic strategy to attenuate age-related inflammation and cognitive decline.

Temporal and sequential order of nonoverlapping gene networks unraveled in mated female Drosophila

In this study, we reanalyzed available datasets of gene expression changes in female Drosophila head induced by mating. Mated females present metabolic phenotypic changes and display behavioral characteristics that are not observed in virgin females, such as repulsion to male sexual aggressiveness, fidelity to food spots selected for oviposition, and restriction to the colonization of new niches. We characterize gene networks that play a role in female brain plasticity after mating using AMINE, a novel algorithm to find dysregulated modules of interacting genes. The uncovered networks of altered genes revealed a strong specificity for each successive period of life span after mating in the female head, with little conservation between them. This finding highlights a temporal order of recruitment of waves of interconnected genes which are apparently transiently modified: the first wave disappears before the emergence of the second wave in a reversible manner and ends with few consolidated gene expression changes at day 20. This analysis might document an extended field of a programmatic control of female phenotypic traits by male seminal fluid.

Sexually Dimorphic Transcriptomic Changes of Developing Fetal Brain Reveal Signaling Pathways and Marker Genes of Brain Cells in Domestic Pigs

In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.

Defining dysfunction due to loss of MECP2 in Rett Patient Brain

Rett Syndrome is characterized by a postnatal loss of neurophysiological function and regression of childhood development. Because the syndrome is X-linked and males with MECP2 mutations generally do not survive birth, the study of this syndrome has been complicated by the fact that in female brain, a portion of neurons express wild type MECP2, and another portion express a non-functional allele of MECP2. Therefore, bulk-RNA-sequencing of Rett brain is confounded by the presence of chimerism of neurons for functional MECP2 in neurons. We developed an approach that allows for single-nuclei transcriptional profiling of individual neurons and a direct comparison between neurons that express functional MECP2 with those that express the disease-causing allele. We found that mutant neurons from Rett brain show patterns of aberrant expression of synaptic and metabolic genes, both of which can be detected in in vitro models of Rett Syndrome. We used these resources to identify a role for POU2F1/OCT1 transcription factor in mediating the response to stress due to loss of MECP2, highlighting a potential key molecular regulator of stress in Rett neurons. Together, our new sorting approach enables us to highlight defective molecular and metabolic pathways in Rett brain neurons and suggests that in vitro models could serve as valuable tools to further study this syndrome and potentially for development of novel therapeutics.

Estrogens and female developing brain: two sides of the coin

The review highlights current views and hypotheses on the pathogenetic role of natural and xenoestrogens in the disorders of programming of neuroendocrine regulation of reproduction, alaptation, and various forms of instinctive behavior (reproductive, eating, parental, etc.) in the perinatal period of development of the female brain. Catecholestrogens, which are formed in the brain as a result of sequential metabolic conversions of testosterone, are involved in exogenous or endogenous androgen-induced defeminization of hypothalamic control of ovulation in early female ontogenesis. In the research on female animals with a knocked out gene of alpha-fetoprotein, the protective role of this protein against the possible pathogenic effect of placental estrogens on the developing brain of female fetuses was proved. The damaging effect of phytoestrogens (genistein, coumestrol) in the early postnatal period on the formation of ovulatory cycles has been shown. Evidence from studies in rodents and other animal species, supported by clinical observations, indicate the potential damaging effect of exposure to low levels of environmental xenoestrogens on the developing brain, in particular on its sexual differentiation and the hypothalamic-pituitary-adrenal axis. The potential hazard of the perinatal exposure to low doses of bisphenol A for the formation of estrogen receptors in the hypothalamus and amygdala of the female brain, sexual behavior and ovulation is discussed. Special attention is paid to the possible physiological role of natural estrogens in the formation of the female neuroendocrine system during puberty. It was concluded that in the early stages of female life, estrogens play a different role in the programming of the neuroendocrine system and behavior, depending on the period of individual development.

One-week escitalopram intake shifts excitation-inhibition balance in the healthy female brain

Background: Neural health relies on cortical excitation-inhibition balance (EIB), with disrupted EIB underlying circuit dysfunction in several neuropsychiatric disorders. Previous research suggests links between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. To this end, we assessed changes in EIB following longitudinal escitalopram-intake. Methods: In a randomized, double-blind study protocol, a sample of 59 healthy female individuals on oral contraceptives underwent three resting-state electroencephalography recordings after daily administration of 20 mg escitalopram (n = 28) or placebo (n = 31) at baseline, after single dose, and after 1 week (steady state).We assessed 1/f slope of the power spectrum, a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Results: Escitalopram-intake associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after single dose of escitalopram predicted 1/f slope at steady state. Higher plasma escitalopram levels at single dose associated with better maintenance of these EIB changes throughout the drug administration week. Conclusions: Characterizing changes in 1/f slope during longitudinal SSRI-intake in healthy female individuals, we show that escitalopram shifted EIB in favor of excitation. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the neuroimaging lens by testing an interventional psychopharmacological design in a clearly-defined endocrinological state.

Gender differences in language development, acquisition, comprehension, and production

In this 21st century, human being is not separated with theories about gender and language which has been established from the simultaneous researches with the aim is to see a novelty on that issue. This paper summarizes findings about gender differences in language development, gender differences in language acquisition focusing on male and female brain function in acquiring language in this case English as a foreign language (EFL), gender differences in language comprehension, and gender differences in language production. The implications to teaching and learning further are presented

How different are women and men?

Books Reviewed: The Better Half: On the Genetic Superiority of Women by Sharon Moalem (Penguin, April 2020) The Gendered Brain: The New Neuroscience that Shatters the Myth of the Female Brain by Gina Rippon (The Bodley Head, February 2019) Gender Mosaic: Beyond the Myth of the Male and Female Brain by Daphna Joel and Luba Vikhanski (Hachette, September 2019) Sexing the Body: Gender Politics and the Construction of Sexuality by Anne Fausto-Sterling (Basic Books, June 2020)