Vertebrate-specific glutaredoxin is essential for brain development

Cellular functions and survival are dependent on a tightly controlled redox potential. Currently, an increasing amount of data supports the concept of local changes in the redox environment and specific redox signaling events controlling cell function. Specific protein thiol groups are the major targets of redox signaling and regulation. Thioredoxins and glutaredoxins catalyze reversible thiol-disulfide exchange reactions and are primary regulators of the protein thiol redox state. Here, we demonstrate that embryonic brain development depends on the enzymatic activity of glutaredoxin 2. Zebrafish with silenced expression of glutaredoxin 2 lost virtually all types of neurons by apoptotic cell death and the ability to develop an axonal scaffold. As demonstrated in zebrafish and in a human cellular model for neuronal differentiation, glutaredoxin 2 controls axonal outgrowth via thiol redox regulation of collapsin response mediator protein 2, a central component of the semaphorin pathway. This study provides an example of a specific thiol redox regulation essential for vertebrate embryonic development.     

Anti-NMDA receptor encephalitis after TdaP–IPV booster vaccination: cause or coincidence?

Journal of Neurology -     

Genetic analysis of tuberous-sclerosis genes 1 and 2 in nonlesional focal epilepsy

Germline mutations of TSC1 (harmartin) and TSC2 (tuberin) are known to cause tuberous sclerosis (TSC), an autosomal dominant disorder with severe neurological and systemic manifestations. In addition, increasing data indicate aberrant patterns of allelic variants in patients with lesion-associated epilepsy, but absence of other stigmata of TSC. Animal models of TSC suggested that mutations in the TSC2 gene, even in absence of manifest neuropathological changes, induce aberrant neuronal activity. On this basis, we have carried out a mutational analysis of TSC1 and TSC2 in patients with pharmarcoresistant focal epilepsy without evidence of epileptogenic lesions on neuroradiological and histopathological examination (n=10). SSCP analysis revealed an allelic variant of TSC2 to be significantly increased (exon 41: 50.0% vs controls 14%, P=0.0132), which previously was reported to be increased in gangliogliomas and mineralized focal cortical dysplasia as well. Our data suggest allelic imbalances of TSC2 in nonlesional focal epileptic tissue.     

Neurodevelopmental disruption in early-onset temporal lobe epilepsy: evidence from a voxel-based morphometry study

Childhood onset of epilepsy has long been associated with an adverse impact on brain development and cognition. In this study it is proposed that earlier (vs later) onset of temporal lobe epilepsy (TLE) has a negative developmental impact on distant brain structures. One hundred ten patients with TLE were assigned to early (≤14 years, N=58) and late (>15 years, N=52) age at onset of epilepsy groups. Voxel-based morphometry revealed onset-dependent abnormalities (in terms of a gray matter excess in the early-onset group), which were found mainly in frontal regions. An excess of gray matter is not a usual finding in TLE. However, within a neurodevelopmental framework, retained gray matter is discussed as reflecting neurodevelopmental disruption. The findings indicate the importance of quantitative MRI for the detection of subtle secondary abnormalities in focal TLE and once more underline the importance of early seizure management in children with intractable TLE.     

Aortic dissection associated with cogans's syndrome: deleterious loss of vascular structural integrity is associated with GM-CSF overstimulation in macrophages and smooth muscle cells

Background  

Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory ocular disease and vestibuloauditory symptoms. Systemic vasculitis is found in about 10% of cases.