Sex/gender influences on the nervous system: Basic steps toward clinical progress

Brooks, Claudette E.; Clayton, Janine Austin

doi:10.1002/jnr.23902

Cited by 20 publications

(15 citation statements)

References 21 publications

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“…Our findings, while corroborating and complementing previous studies (39)(40)(41)(42)(43), link SRC with a sex biologic divergence of a circulating neuroaxonal injury marker, namely t-tau, demonstrating their association with adverse clinical outcomeslonger RTP. We interpret these results as emphasizing the need for increased awareness of sex-related SRC variability and clinical relevance, and for more extensive research to unearth and elucidate the neurobiological underpinnings of sex-differences in biomedicine, particularly following sports-concussions (44)(45)(46).…”

Section: Discussionmentioning

confidence: 92%

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

et al. 2020

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Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological processes and disease mechanisms. Such knowledge will help improve diagnosis, clinical management, and prognosis. Total-tau (t-tau) has recently emerged as a promising blood marker showing sex-associated differences in neurodegenerative diseases. Nonetheless, to date, little is known about the potential influence of sex on its injury-related concentration and dynamics after SRC. We hypothesized that measurements of circulating levels of t-tau over time would reflect a differential vulnerability signature, providing insights into the sex-related phenotypes and their relationship with clinical outcomes. To test this hypothesis, plasma levels of t-tau were measured using an ultrasensitive immunoassay up to 7 days after injury, in 46 concussed athletes (20 males, 26 females). We used trajectory analysis to generate two distinct temporal profiles of t-tau, which were then compared with gender and return to play (RTP). The majority of subjects (∼63%) started with low t-tau concentrations that further declined within the first 48 h; while the remaining ("maximal decliners") started with concentrations comparable to the baseline levels that also fell over time, but persisting markedly higher compared with the first profile. The maximal decliner group was primarily composed of female subjects (p = 0.007) and was significantly associated with poor outcome (RTP ≥ 10 days after concussion) (p = 0.011). Taken together, our data provide evidence for the existence of sex-related biosignatures following sports-related concussions, possibly indicating a differential effect as a result of distinct brain vulnerability and inherent injury response. Future studies will be required to further elucidate underlying sex-based biological and pathophysiological mechanisms, and determine the value of t-tau signatures for management and therapeutic decision-making in sports-related concussions.

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Section: Discussionmentioning

confidence: 92%

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

et al. 2020

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“…It was previously believed that sex-dependent differences in the brain are mainly related to brain functions in the context of reproduction. However, it has lately become clear that sex has an influence not only on areas regulating reproductive behavior, but also on general neurobiology and neurophysiology during brain development [19]. Already in utero, gonadal steroid hormones mediate sex differences on brain structure and function, including neurogenesis, synaptic pruning, dendritic branching, axonal growth, myelination, and apoptosis [20].…”

Section: Sex-dependent Effects On Physiological Brain Developmentmentioning

confidence: 99%

Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro-Psychiatric Disorders

Ardalan

Chumak

Vexler

et al. 2019

IJMS

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Individuals born preterm have higher rates of neurodevelopmental disorders such as schizophrenia, autistic spectrum, and attention deficit/hyperactivity disorders. These conditions are often sexually dimorphic and with different developmental trajectories. The etiology is likely multifactorial, however, infections both during pregnancy and in childhood have emerged as important risk factors. The association between sex- and age-dependent vulnerability to neuropsychiatric disorders has been suggested to relate to immune activation in the brain, including complex interactions between sex hormones, brain transcriptome, activation of glia cells, and cytokine production. Here, we will review sex-dependent effects on brain development, including glia cells, both under normal physiological conditions and following perinatal inflammation. Emphasis will be given to sex-dependent effects on brain regions which play a role in neuropsychiatric disorders and inflammatory reactions that may underlie early-life programming of neurobehavioral disturbances later in life.

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“…The evolutionary distance from humans might be a limitation, especially when studying complex conditions. Self-fertilization and the scarcity of males in wild type (WT) population make it difficult to study sex-specific differences, an approach currently promoted in neuroscience, including developmental neurotoxicology, and in other fields (Brooks and Clayton, 2017).…”

Section: C Elegans In Neurosciencementioning

confidence: 99%

C. elegans as a model in developmental neurotoxicology

Ruszkiewicz

Pinkas

Miah

et al. 2018

Toxicology and Applied Pharmacology

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Due to many advantages Caenorhabditis elegans (C. elegans) has become a preferred model of choice in many fields, including neurodevelopmental toxicity studies. This review discusses the benefits of using C. elegans as an alternative to mammalian systems and gives examples of the uses of the nematode in evaluating the effects of major known neurodevelopmental toxins, including manganese, mercury, lead, fluoride, arsenic and organophosphorus pesticides. Reviewed data indicates numerous similarities with mammals in response to these toxins. Thus, C. elegans studies have the potential to predict possible effects of developmental neurotoxicants in higher animals, and may be used to identify new molecular pathways behind neurodevelopmental disruptions, as well as new toxicants.

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Sex/gender influences on the nervous system: Basic steps toward clinical progress

Cited by 20 publications

References 21 publications

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro-Psychiatric Disorders

C. elegans as a model in developmental neurotoxicology

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