Androgens Contribute to the Process of Neuronal Development: Implications in Explanation of Autism Pathogenesis

Abstract

Fetal testosterone significantly influences the brain development. It affects number of neurons and conformation of dendritic spines within the sexual dimorphic preoptic area in the hypothalamus. Excessive testosterone levels in utero possibly contribute to the masculinization of the brain. Evidences of these facts are plausible in the anatomic field as well as behavioral effects both in rat models and in humans. Rats exposed to excessive testosterone doses in utero show masculinized brain anatomy and behavior, such as better spatial visualization performance typical for males. In humans, congenital adrenal hyperplasia that causes elevated androgen level possibly results in masculinized behavior observed in these individuals. There are reasons for the theory of the connection existence between testosterone influence on the brain functions and the pathogenesis of neurodevelopmental disorders. In this review, pathogenesis of autism, the most genetic neurodevelopmental disease is discussed. Autism is a disease with broad genetic heterogeneity and polygenic inheritance. Autism associated genes are localized throughout the genome, with the chromosome 7q most frequently involved. One of these genes encodes reelin protein that is crucial for neuronal migration in the developing brain. The connection between androgens, neuronal migration and neurodevelopmental disorder pathophysiology is also discussed.

Anthropometric measures do not explain the 2D:4D ratio sexual dimorphism in 7‐year‐old children

“…Thus, as 2D:4D might provide an insight in fetal milieu, publications have focused on 2D:4D as a predictor for diseases of fetal origin. For example, association between low 2D:4D and presence of neuro developmental disorders (NDDs) (Al‐Zaid et al, 2015; De et al, 2007; Manning et al, 2001), impairments thought to partly arise from androgenic effect on fetal neurodevelopment (Kelemenova & Ostatnikova, 2008). Similarly, 2D:4D have also been utilized in investigations regarding correlation with other human traits like depression (Bailey & Hurd, 2005) and cardiovascular risk factors (Oyeyemi et al, 2014).…”

Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases

“…In the adult brain, it is mainly secreted by a subset of cortical GABA-ergic interneurons, cerebellar granule cells, and hippocampal interneurons [21,22] and modulates synaptic plasticity [14,23], migration of neuroblasts [24], as well as dendrite [25] and dendritic spine [26] formation. Reelin expression in the central nervous system (CNS) has been implicated in a wide range of neurodegenerative diseases, such as Alzheimer's disease (AD), cognitive disorders, such as autism spectrum disorder, and neuropsychiatric disorders, 2 of 17 such as schizophrenia and bipolar disorder [15,[27][28][29][30][31][32][33][34][35][36][37][38][39]. The nascent Reelin protein consists of a signal peptide, succeeded by an F-spondin-like domain, eight Reelin repeats featuring an epidermal growth factor (EGF)-like cysteine pattern that separates each repeat into subdomains A and B, and finally, a positively charged C terminus [40,41].…”