03), CA2 sector of the hippocampus (P = 0.01) and entorhinal cortex (P = 0.04) in PD cases with disturbed sleep. Pathological changes in these structures, residing in the brain circuitry relating to sleep physiology, strongly predict the presence of sleep disturbances in PD. “
“As 4-day-old mice of the severe spinal muscular atrophy (SMA) model (dying at 5–8 days) display pronounced neuromuscular changes in the diaphragm but not the soleus muscle, we wanted to gain more insight into the relationship between muscle development and the emergence of pathological changes

and additionally to analyse intercostal muscles which are affected in human SMA. Structures of muscle fibres and neuromuscular junctions (NMJs) of the diaphragm, intercostal and calf muscles of prenatal (E21) and postnatal (P0 and P4) healthy and SMA mice Epigenetics Compound Library supplier were analysed by light and transmission electron microscopy. NMJ innervation was studied by whole mount immunofluorescence Autophagy Compound Library manufacturer in diaphragms of P4 mice. During this period, the investigated muscles still show a significant neck-to-tail developmental

gradient. The diaphragm and calf muscles are most and least advanced, respectively, with respect to muscle fibre fusion and differentiation. The number and depth of subsynaptic folds increases, and perisynaptic Schwann cells (PSCs) acquire a basal lamina on their outer surface. Subsynaptic folds are connected to an extensive network of tubules and beaded caveolae, reminiscent of the T system in adult muscle. Interestingly, intercostal muscles from P4 SMA mice show weaker pathological involvement (that is, vacuolization of PSCs and perineurial cells) than those previously described by us for the diaphragm, whereas calf muscles show no selleck kinase inhibitor pathological changes. SMA-related alterations appear to occur only when the muscles have reached a certain developmental maturity.

Moreover, glial cells, in particular PSCs, play an important role in SMA pathogenesis. “
“Frontotemporal lobar degeneration (FTLD) and Motor Neuron Disease are linked by the possession of a hexanucleotide repeat expansion in C9ORF72, and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are TDP-43 negative but immunoreactive for p62 and dipeptide repeat proteins (DPR), these being generated by a non-ATG RAN translation of the expanded region of the gene. Twenty two cases of FTLD from Newcastle were analyzed for an expansion in C9ORF72 by repeat primed PCR and Southern blot. Detailed case note analysis was performed, and blinded retrospective clinical impressions were achieved by review of clinical histories. Sections from all major brain regions were immunostained for TDP-43, p62 and DPR. The extent of TDP-43 and DPR pathology in expansion bearers was compared to that in 13 other previously identified cases from the Manchester Brain Bank with established disease. Three Newcastle patients bearing an expansion in C9ORF72 were identified.