Sleep Disorder Kleine-Levin Syndrome (KLS) Joins the List of Polygenic Brain Disorders Associated with Obstetric Complications.

Kleine-Levin Syndrome is a rare neurological disorder with onset typically during adolescence that is characterized by recurrent episodes of hypersomnia, behavioral changes, and cognitive abnormalities, in the absence of structural changes in neuroimaging. As for many functional brain disorders, the exact disease mechanism in Kleine-Levin Syndrome is presently unknown, preventing the development of specific treatment approaches or protective measures. Here we review the pathophysiology and genetics of this functional brain disorder and then present a specific working hypothesis.

New aspects for the brain in Hartnup disease based on mining of high-resolution cellular mRNA expression data for SLC6A19.

Hartnup disease is an autosomal recessive, metabolic disorder caused by mutations of the neutral amino acid transporter, SLC6A19/B0AT1. Reduced absorption in the intestine and kidney results in deficiencies in neutral amino acids and their down-stream metabolites, including niacin, associated with skin lesions and neurological symptoms. The effects on the nervous system such as ataxia have been related to systemic deficiencies of tryptophan (and other neutral amino acids) as no expression of the B0AT1 transporter was found in the brain.

Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain.

Obstetric complications (OCs) can induce major adverse conditions for early brain development and predispose to mental disorders, including schizophrenia (SCZ). We previously hypothesized that SCZ candidate genes respond to ischemia-hypoxia as part of OCs which impacts neurodevelopment. We here tested for an overlap between SCZ genes from genome-wide association study (GWAS) (n=458 genes from 145 loci of the most recent GWAS dataset in SCZ) and gene sets for ischemia-hypoxia response.

Methionine sulfoxide reductase (Msr) dysfunction in human brain disease.

Extensive research has shown that oxidative stress is strongly associated with aging, senescence and several diseases, including neurodegenerative and psychiatric disorders. Oxidative stress is caused by the overproduction of reactive oxygen species (ROS) that can be counteracted by both enzymatic and nonenzymatic antioxidants. One of these antioxidant mechanisms is the widely studied methionine sulfoxide reductase system (Msr).

Involvement of hemoglobins in the pathophysiology of Alzheimer's disease.

Hemoglobins (Hbs) are heme-containing proteins binding oxygen, carbon monoxide, and nitric oxide. While erythrocytes are the most well-known location of Hbs, Hbs also exist in neurons, glia and oligodendroglia and they are primarily localized in the inner mitochondrial membrane of neurons with likely roles in cellular respiration and buffering protons. Recently, studies have suggested links between hypoxia and neurodegenerative disorders such as Alzheimer Disease (AD) and furthermore suggested involvement of Hbs in the pathogenesis of AD.