Sex differences in the blood–brain barrier and neurodegenerative diseases

Weber, Callie M.; Clyne, Alisa Morss

doi:10.1063/5.0035610

Cited by 56 publications

(36 citation statements)

References 185 publications

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“…Only a handful of studies have explored BBB sex differences, most indirectly and in vitro 37 but, to our knowledge, none did so in the context of chronic stress in mice or MDD. Overall, our findings indicate that chronic social and subchronic variable stressors alter BBB integrity in the mouse female brain through loss of the tight junction protein Cldn5 in the PFC and, to some extent, other mood-related brain regions such as the NAc.…”

Section: Discussionmentioning

confidence: 99%

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

et al. 2022

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Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.

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Section: Discussionmentioning

confidence: 99%

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

et al. 2022

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“…Only a handful of studies have explored BBB sex differences, most indirectly and in vitro 33 but, to our knowledge, none did so in the context of chronic stress in mice or MDD. Overall, our findings indicate that chronic social and subchronic variable stressors alter BBB integrity in the mouse female brain through loss of the tight junction protein cldn5 in the PFC and, to some extent, other mood-related brain regions such as the NAc.…”

Section: Discussionmentioning

confidence: 99%

Sex-specific blood-brain barrier alterations and vascular biomarkers underlie chronic stress responses in mice and human depression

Dion‐Albert

Cadoret

Doney

et al. 2021

Preprint

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Prevalence, symptoms, and treatment of depression all point toward major sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice however it remains unknown if it contributes to this sexual dimorphism. Here, we report that chronic social and subchronic variable stress promoted sex-specific blood-brain barrier (BBB) molecular and morphological alterations in mood-related brain regions. Viral-mediated functional manipulation leading to a targeted disruption of the BBB induced anxiety- and depression-like behaviors including social avoidance and anhedonia. Endothelium cell-specific transcriptomic profiling revealed key pathways and novel genes involved in maladaptive stress responses vs resilience. We also confirmed BBB leakiness in the brain of stressed females which led us to explore and identify circulating vascular biomarkers of chronic stress that could inform on diagnosis and treatment. Importantly, these pre-clinical findings were validated in human blood and postmortem brain samples from depressed women, thus highlighting their translational value. By revealing a sex-specific causal role of BBB dysfunction in stress responses and depression, our results implicate vascular impairment as a major factor underlying mood disorders.

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“…The consequent clinical symptoms, both motor and cognitive, vary and are characteristic of the specific disorder. Moreover, neurodegenerative disorders can be age-related or non-age-related and sex-biased and be either familiar or sporadic [ 4 , 26 , 31 , 103 , 104 ]. LncRNAs play a significant role in the pathophysiology of these disorders due to their important regulatory functions within the cell, involvement in various signalling pathways and the functioning of mitochondria; hence, their dysregulation may lead to the death of neurons and brain atrophy ( Table 1 ) [ 26 , 105 , 106 ].…”

Section: Lncrnas In Neurological and Neurodegenerative Disordersmentioning

confidence: 99%

Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders

Aliperti

Skonieczna

Cerase

2021

ncRNA

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Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders.

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Sex differences in the blood–brain barrier and neurodegenerative diseases

Cited by 56 publications

References 185 publications

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

Sex-specific blood-brain barrier alterations and vascular biomarkers underlie chronic stress responses in mice and human depression

Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders

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