Flowers for Algernon: steroid dysgenesis, epigenetics and brain disorders.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 6
Abstract
While a recent study has reported that early citalopram exposure alters cortical network function and produces autistic-like behaviors in male rats, when evaluating antidepressant animal models of autism spectrum disorder (ASD) it is important to note that some selective serotonin (5-HT) reuptake inhibitors alter 3α-hydroxysteroid dehydrogenase activity, and thus steroidogenesis. At least one study has examined the effect of repeated citalopram administration on the serum and brain concentration of testosterone (T) and its metabolites and shown that citalopram increases serum T. Several in vitro studies also suggest that sex steroid can alter 5-HT homeostasis. While research efforts have demonstrated that transgenic mice expressing the most common of multiple gain-of-function 5-HT reuptake transporter (SERT) coding variants, SERT Ala56, previously identified in children with ASD, exhibit autistic-like behaviors, elevated p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia, a few studies provide some evidence that 5-HT may alter gonadal steroidogenesis. T, 17β-estradiol and synthetic estrogens are known inhibitors of AKR1C21 (BRENDA, E.C. 1.1.1.209), the epitestosterone (epiT) producing enzyme in rodents. EpiT is a naturally occurring steroid in mammals, including man. An analysis of the literature suggests that epiT may be the central mediator in the epigenetic regulation of gene expression. Over thirty years ago, it was shown that rat brain epiT production is higher in females than in males. A similar finding in humans could explain the sex differences in the incidence of autism and other brain disorders. Despite this, the role of epiT in brain development remains a long neglected area of research.
Authors and Affiliations
Bryan Sanders
Keywords
Related Articles
- EP ID EP135729
- DOI -
- Views 113
- Downloads 0
Influence of 5-(3-chlorophenyl)-4-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione on the anticonvulsant action of 4 classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
Background: The aim of this study was to determine the effects of 5-(3-chlorophenyl)-4-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP10) on the protective action of 4 classical antiepileptic drugs - carbamaz...
Magnesium ions and opioid agonists in vincristine-induced neuropathy.
Neuropathic pain is difficult to treat. Classic analgesics (i.e., opioid receptor agonists) usually possess low activity. Therefore other agents such as antidepressants, anticonvulsants, and corticosteroids are used. It...
Imidazoline receptors in relaxation of acetylcholine-constricted isolated rat jejunum.
Since 20 years the concept of specific imidazoline receptors has remained controversial. The problem with imidazoline receptors is mostly due to their functional similarity to alpha-adrenoceptors. In this work, a pharmac...
Contribution of NO, ATP-sensitive K+ channels and prostaglandins to adenosine receptor agonists-induced relaxation of the rat tail artery.
The mechanism of relaxation in the rat tail artery induced by the adenosine A(1) receptor-selective agonist N(6)-cyclohexyladenosine (CHA, 10 nM-300 microM) and the adenosine A1/A(2a) receptor agonist 5'-N-ethylcarboxami...
Atherosclerosis and angiogenesis: what do nerves have to do with it?
Neuropeptide Y (NPY) is a sympathetic neurotransmitter and a stress mediator with pleiotropic activities mediated by multiple receptors, Y1-Y5. Originally known as an appetite stimulant and a vasoconstrictor, NPY has rec...