White and grey matter abnormalities in patients with SPG11 mutations.

BACKGROUND: Mutations in SPG11 are the most frequent known cause of autosomal recessive hereditary spastic paraplegia. Corpus callosum thinning is a hallmark of the condition but little is known about damage to other structures in the CNS. OBJECTIVE: To evaluate in vivo cerebral damage in patients with SPG11 mutations. METHODS: 5 patients and 15 age and sex matched healthy controls underwent high resolution diffusion tensor imaging (32 directions) and a T1 volumetric (1 mm slices) acquisition protocol in a 3 T scanner (Philips Achieva). These sequences were then analysed through voxel based morphometry (VBM) and tract based spatial statistics (TBSS). RESULTS: Mean age of the patients was 23.6±4.5 years (range 14-45) and mean duration of disease was 12 years (range 5-15). All patients presented with progressive spastic paraplegia and three were already wheelchair bound when first evaluated. Mutations found were: c.529_533delATATT, c.704_705delAT, c.733_734delAT, c.118C>T and c.7256A>G. VBM identified significant grey matter atrophy in both the thalamus and lentiform nuclei. TBSS analyses revealed reduced fractional anisotropy involving symmetrically subcortical white matter of the temporal and frontal lobes, the cingulated gyrus, cuneus, striatum, corpus callosum and brainstem. CONCLUSIONS: Widespread white matter damage in patients with SPG11 mutations has been demonstrated. Grey matter atrophy was prominent in both the thalamus and basal ganglia but not in the cerebral cortex. These findings suggest that neuronal damage/dysfunction is more widespread than previously recognised in this condition.

Partial reversibility of hypothalamic dysfunction and changes in brain activity after body mass reduction in obese subjects.

OBJECTIVE: Inflammation and dysfunction of the hypothalamus are common features of experimental obesity. However, it is unknown whether obesity and massive loss of body mass can modify the immunologic status or the functional activity of the human brain. Therefore, the aim of this study was to determine the effect of body mass reduction on brain functionality. RESEARCH DESIGN AND METHODS: In humans, changes in hypothalamic activity after a meal or glucose intake can be detected by functional magnetic resonance imaging (fMRI). Distinct fMRI analytic methods have been developed to explore changes in the brain's activity in several physiologic and pathologic conditions. We used two analytic methods of fMRI to explore the changes in the brain activity after body mass reduction. RESULTS: Obese patients present distinct functional activity patterns in selected brain regions compared with lean subjects. On massive loss of body mass, after bariatric surgery, increases in the cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 are accompanied by changes in fMRI patterns, particularly in the hypothalamus. CONCLUSIONS: Massive reduction of body mass promotes a partial reversal of hypothalamic dysfunction and increases anti-inflammatory activity in the CSF.

Transcription of succinate dehydrogenase subunit 4 (sdh4) gene in potato: detection of extensive RNA editing and co-transcription with cytochrome oxidase subunit III (cox3) gene.

The potato (Solanum tuberosum L.) mitochondrial cox3/ sdh4 gene cluster was previously identified by heterologous hybridization using a Marchantia polymorpha sdh4 probe. In this work, this potato gene cluster was cloned, sequenced and its expression was evaluated. The gene sequence and gene locus organization were found to be similar to the corresponding gene cluster in other dicot species, where known. Northern hybridizations with potato and cauliflower (Brassica oleraceae) mtRNA and RT-PCR analyses using potato mtRNA indicated that cox3 and sdh4 are co-transcribed in both species, generating a complex transcription pattern, where several transcripts from 1.1 kb to 4.4 kb are found. The potato transcript from this cluster displayed 14 and 13 RNA-editing sites, in the cox3 and sdh4 genes respectively, which changed the codon identity to amino acids and created a sdh4 partially edited stop codon. Forty-three cDNA clones were analyzed for editing process and revealed different partial-editing with no apparent sequential processing in the sdh4 gene.