Maternal stress programs a demasculinization of glutamatergic transmission in stress-related brain regions of aged rats

Abstract

Brain aging may be programmed by early-life stress. Aging affects males and females differently, but how perinatal stress (PRS) affects brain aging between sexes is unknown. We showed behavioral and neurobiological sex differences in non-stressed control rats that were strongly reduced or inverted in PRS rats. In particular, PRS decreased risk-taking behavior, spatial memory, exploratory behavior, and fine motor behavior in male aged rats. In contrast, female aged PRS rats displayed only increased risk-taking behavior and reduced exploratory behavior. PRS induced large reductions in the expression of glutamate receptors in the ventral and dorsal hippocampus and prefrontal cortex only in male rats. PRS also reduced the expression of synaptic vesicle-associated proteins, glucocorticoid receptors (GR), and mineralocorticoid receptors (MR) in the ventral hippocampus of aged male rats. In contrast, in female aged rats, PRS enhanced the expression of MRs and brain-derived neurotrophic factor (BDNF) in the ventral hippocampus and the expression of glial fibrillary acidic protein (GFAP) and BDNF in the prefrontal cortex. A common PRS effect in both sexes was a reduction in exploratory behavior and metabotropic glutamate (mGlu2/3) receptors in the ventral hippocampus and prefrontal cortex. A multidimensional analysis revealed that PRS induced a demasculinization profile in glutamate-related proteins in the ventral and dorsal hippocampus and prefrontal cortex, as well as a demasculinization profile of stress markers only in the dorsal hippocampus. In contrast, defeminization was observed only in the ventral hippocampus. Measurements of testosterone and 17-β-estradiol in the plasma and aromatase in the dorsal hippocampus were consistent with a demasculinizing action of PRS. These findings confirm that the brains of males and females differentially respond to PRS and aging suggesting that females might be more protected against early stress and age-related inflammation and neurodegeneration. Taken together, these results may contribute to understanding how early environmental factors shape vulnerability to brain aging in both sexes and may lay the groundwork for future studies aimed at identifying new treatment strategies to improve the quality of life of older individuals, which is of particular interest given that there is a high growth of aging in populations around the world.

High Seroprevalence of SARS-COV-2 Antibody before Covid-19 Vaccination in Nigerian Communities

“…This finding deserves further investigation because previous studies found that men had higher SARS-CoV-2 infectivity rates compared to women [39][40][41][42], and male participants with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the infection, with increased mortality rate [43,44]. Many factors such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection were suggested [41,42,[45][46][47][48].…”

Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity

“…Further, rodent models suggest perinatal stress exposure may lead to the demasculinization of the developing fetal brain, documenting decreased testosterone and increased estradiol levels in exposed males, but not females, further suggesting a role for endocrine disruptions following adversity exposure. 59 However, our understanding of these sex-specific processes remains limited. It is important to note whereas in the broader (i.e., non-infant neuroimaging) literature of intergenerational adversity there are a number of studies that have documented increased susceptibility in males, there are exceptions.…”

Sexual Dimorphism in the Effect of Neonatal Inflammatory Pain on Stress Reactivity of Hormonal Response and Cognitive Functions in Adult Rats

“…During postnatal development, the NR2B is replaced by the NR2A receptor subunit. Excessive levels of glucocorticoids increase glutamate release [ 41 ], causing neurotoxicity, which increases apoptosis, as shown in the hippocampus and other brain regions during the first postpartum week in rats [ 42 , 43 ]. It has been shown, for example, that selective loss of the NR2B protein and subsequent synaptic dysfunction weaken the function of the prefrontal cortex during development and provoke the appearance of early cognitive impairments [ 44 ].…”