Steroids, sex and the cerebellar cortex: implications for human disease

Abstract

Neurosteroids play an important role in the development of the cerebellum. In particular, estradiol and progesterone appear capable of inducing increases in dendritic spine density during development, and there is evidence that both are synthesized de novo in the cerebellum during critical developmental periods. In normal neonates and adults, there are few differences in the cerebellum between the sexes and most studies indicate that hormone and receptor levels also do not differ significantly during development. However, the sexes do differ significantly in risk of neuropsychological diseases associated with cerebellar pathology, and in animal models there are noticeable sex differences in the response to insult and genetic mutation. In both humans and animals, males tend to fare worse. Boys are more at risk for autism and Attention Deficit Hyperactivity Disorder than girls, and schizophrenia manifests at an earlier age in men. In rats males fare worse than females after perinatal exposure to polychlorinated biphenyls, and male mice heterozygous for the staggerer and reeler mutation show a more severe phenotype. Although very recent evidence suggests that differences in neurosteroid levels between the sexes in diseased animals may play a role in generating different disease phenotypes, the reason this hormonal difference occurs in diseased but not normal animals is currently unknown.

Early methyl donor deficiency alters cAMP signaling pathway and neurosteroidogenesis in the cerebellum of female rat pups

“…These alterations of the neurosteroidogenesisrelated proteins may participate in the previously documented impaired locomotor coordination involving cerebellar functions in the same animal model of methyl donor deficiency (5). In addition, the cerebellum is also involved in cognitive tasks through the coordination of the cortico-thalamic-cerebellarcortical circuit (10), and our observations may also account for the impaired learning capacities and memory documented previously in deficient rat pups (5).…”

Maternal Prenatal Weight Gain and Autism Spectrum Disorders

“…Steroid hormones in the fetal environment are environmental factors that directly affect fetal gene transcription and expression through DNA binding during vulnerable periods of embryonic development. [5][6][7][8] Termed the "maternofetoplacental unit," mother, fetus, and placenta collectively create the in utero steroid environment through the complex exchange of steroid precursors. 9 A disturbance in this steroid production, hereafter referred to as "in utero steroid dysregulation," may be a potentially modifiable ASD environmental risk factor.…”

Gender Differences in Human Brain: A Review

“…Dorsal raphe nucleus (DRN) is the largest of all raphe nuclei in rat brain stem, and a part of serotonergic system [206]. Studies have also indentified many areas of the brain that are altered during development due to exposure to sex steroids, not only areas closely connected with reproduction, but also in the areas important for emotional responses such as amygdala and even other areas such as hippocampus and cerebellum [207,208]. Substantial evidence indicates that sex hormones influence learning and memory processes [209], and interact with stress hormones to do so.…”