Biology subjects

Zsido, R. G.

Publications and source records attributed to Zsido, R. G..

3 recordsLinked to original sources

bioRxiv2023

Relating sex differences in cortical and hippocampal microstructure to sex hormones

Sex hormone receptors are expressed widely in both neurons and glial cells, which allows them to interact with the brains major cell groups via several molecular mechanisms. These mechanisms lead to sex differences in brain structure as well as hormone-induced plasticity in the female brain across the menstrual cycle. Adding to the literature on volumetric changes in cortical structure, here we set out to investigate sex differences in the microstructure of the human cortex in relation to sex hormones. We assessed regional variation in cortical microstructure as a function of sex, hormonal status and sex hormone receptor gene expression distribution based on quantitative intracortical profiling in vivo using the magnetic resonance imaging based T1w/T2w ratio in 992 healthy females and males of the Human Connectome Project young adult sample. We demonstrate that microstructure in isocortex and hippocampus differs regionally between males and females, that this effect varies with hormone levels of females and that implicated brain regions overlap with estrogen receptor and sex steroid synthesis gene expression. Lastly, we show that sex and sex hormone related brain structure variations are most pronounced in areas of low laminar cortical complexity (agranular cortex), which are also predicted to be most plastic based on their cytoarchitectural properties. Together, our data thus are suggestive of sex differences in cortical and hippocampal microstructure, as well as the modulatory function of sex hormones on these measures. Albeit correlative, this study underscores the importance of incorporating sex hormone variables into the investigation of brain structure and plasticity.

neuroscience↗

bioRxiv2022

Longitudinal 7T MRI reveals volumetric changes in subregions of human medial temporal lobe to sex hormone fluctuations

The hippocampus and surrounding medial temporal lobe (MTL) are critical for memory processes, with local atrophy linked to memory deficits. Animal work shows that MTL subregions densely express sex hormone receptors and exhibit rapid structural changes synchronized with hormone fluctuations. Such transient effects in humans have thus far not been shown. By combining a dense-sampling protocol, ultra-high field neuroimaging and individually-derived segmentation analysis, we demonstrate how estradiol and progesterone fluctuations affect MTL subregion volumes across the human menstrual cycle. Twenty-seven healthy women (19-34 years) underwent 7T MRI at six timepoints to acquire T1-weighted and T2-weighted images. Linear mixed-effects modeling showed positive associations between estradiol and parahippocampal cortex volume, progesterone and subiculum and perirhinal Area 35 volumes, and an estradiol*progesterone interaction with CA1 volume. We confirmed volumetric changes were not driven by hormone-related water (cerebral spinal fluid) or blood-flow (pulsed arterial spin labeling) changes. These findings suggest that sex hormones alter structural brain plasticity in subregions that are differentially sensitive to hormones. Mapping how endogenous endocrine factors shape adult brain structure has critical implications for womens health during the reproductive years as well as later in life, such as increased dementia risk following perimenopause, a period of pronounced sex hormone fluctuations.

neuroscience↗

bioRxiv2021

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

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. 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. 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. 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.

neuroscience↗