Cognitive deficits are present in a substantial number of Multiple Sclerosis (MS) patients, particularly in those with the chronic-progressive type of the disorder. We assessed cognitive decline and its relationship with T2-weighted images on magnetic resonance imaging (MRI). We submitted a group of 26 patients with progressive MS to both MRI and a battery of neuropsychological tests. Cognitive impairment did not correlate with duration of illness or severity of neurological disability, but rather with the presence of extensive periventricular demyelination on MRI, evaluated as area of confluent lesions. These results suggest that cognitive deficits in MS represent a symptom of disease and not a parallel occurrence.

Adult↗

PubMedDate not supplied

Antidegenerative effects of Mg(2+)-valproate in cultured cerebellar neurons.

We have investigated in the present study the effect of Mg(2+)-valproate on necrotic degeneration induced by an excitotoxic insult in primary culture of cerebellar neurons, that is an homogeneous population of glutamatergic neurons. Mg(2+)-valproate protected cultures against glutamate-induced neurotoxicity, acting as an indirect N-methyl-D-aspartate (NMDA) receptor antagonist, thus reducing free radical formation and affecting the biochemical parameters (i.e. 45Ca(2+)-influx, cyclic GMP formation, inositol phospholipid hydrolysis and protein kinase C translocation) that undergo modifications following NMDA receptor activation in cerebellar granule cells.

Animals↗

PubMedDate not supplied

HPLC analysis of cyclic adenosine diphosphate ribose and adenosine diphosphate ribose: determination of NAD+ metabolites in hippocampal membranes.

Cyclic adenosine diphosphate-ribose (cADPR) and ADPR were separated by high-performance liquid chromatography (HPLC) on a CarboPac PA-1 column at strong basic pH and quantitated by a pulsed amperometric detector. Although this HPLC method was quite sensitive and highly reproducible, it did not allow the separation of cADPR from guanosine monophosphate (GMP) which, when present, could be removed by ion-affinity chromatography, using gel-immobilized Fe3+ columns. Crude synaptic membranes from rat hippocampi were incubated with nicotinamide adenine dinucleotide (NAD) and acidic extracts were subject to HPLC analysis after neutralization. Incubation led to a time-dependent formation of ADPR, which was amplified when membranes were incubated in the presence of guanosine trisphosphate (GTP), guanosine-5'-0-(3-thiotrisphosphate) (GTP-gamma-S) or AlF3. cADPR did not accumulate in detectable amounts and only a minimal proportion (< 5%) of radioactivity originating from [3H]NAD co-eluted with authentic cADPR in extracts from hippocampal membranes. The simultaneous detection of cADPR and ADPR we have described may help the search for inhibitors of cADPR metabolism, which will allow to measure the cADPR that accumulates under basal conditions or in response to extracellular signals.

Adenosine Diphosphate Ribose↗