A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.
Huntington’s disease (HD) is a progressive, non-curative, autosomal dominant neurodegenerative disease characterized by prominent psychiatric problems, as well as progressive deterioration in both cognitive function and motor control. The success of therapeutic interventions in HD patients cannot be easily examined without reliable and practical measurements by using effective biomarkers. Many clinical trials have been held to evaluate biomarkers efficacies in disease-modifying treatment before the manifestation of the disease or its severity. Biofluid (wet) biomarkers have potential advantages of direct quantification of biological processes at the molecular level, imaging biomarkers, on the other hand, can quantify related changes at a structural level in the brain. The most robust biofluid and imaging biomarkers are being investigated for their clinical use and development of future treatment and can offer complementary information, providing a more comprehensive evaluation of disease stage and progression.
Multiple sclerosis (MS) is a central nervous system inflammatory illness that begins with immune system dysregulation and impairs information flow inside the brain as well as between the brain and the rest of the body. The cause of MS is yet unknown. The interplay of genetic predispositions with environmental/lifestyle factors, such as smoking, obesity, viral exposure, and insufficient sun exposure, has led to numerous theories. This is reinforced by a major discovery of gene–environment (GxE) interaction, which could provide information on the disease’s molecular pathways to aid in the identification of new therapy and preventative strategies, as well as steer disease exploration to new lifestyle suggestions. While some persons with the major susceptibility to MS have a human leukocyte antigen (HLA) Class II gene, according to genetic studies. We will cover recent studies relating to several genetic, environmental, and lifestyle factors, as well as their impact on MS, in this chapter.
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