Abstract— The sodium‐dependent high affinity choline uptake into synaptosomes from rat brain has been studied after in vivo treatments which would alter the activity of cholinergic neurons. We utilized a number of treatments to reduce the activity of cholinergc neurons in the brain. Administration of pentobarbital (65 mg/kg), chloral hydrate (40 mg/kg) and γbutyrelactone (750 mg/kg) caused a 50‐80% reduction in sodium‐dependent high affinity choline uptake in several brain regions (30 min). This depression was not found 24 h after injection. Interruption of the cholinergic septal‐hippocampal or habenuleinterpeduncular tracts by lesions (10 min‐1 h) also caused a similar, large reduction in sodium‐dependent high affinity choline uptake in the hippocampus and the interpeduncular nucleus respectively. We reversed the inactivity after pentobarbital administration by direct electrical stimulation of the cholinergic septal‐hippocampal tract. Stimulation (40 Hz) for 10‐15 min completely reversed the depression in sodium‐dependent high affinity choline uptake. Stimulation at lower frequencies or for shorter times caused a partial reversal. Administration of pentylenetetrazol (75 mg/kg), a convulsant, was utilized to increase the activity of central cholinergic neurons. After drug administration, we found a large (60%) increase in sodium‐de‐pendent high affinity choline uptake. This increase was not found in the hippocampus when cholinergic afferents were interrupted by septal lesion prior to drug administration. We also examined the uptake after administration of cholinergic drugs. Oxotremorine (0.75 mg/kg), a muscarinic agonist which reduces acetylcholine release and turnover, caused a reduction in uptake. On the other hand, administration of scopolamine (5 mg/kg), a cholinergic antagonist which increases acetylcholine turnover, caused an increase in sodium‐dependent high affinity choline uptake. Addition of any drug utilized, drectly to uptake samples, did not alter uptake. We examined the conversion of [3H]choline to [3H]acetylcholine in hippocampal synaptosomes after septal lesion, pentylenetetrazol administration and in untreated controls. In all cases, 60‐70% of the total sodium‐dependent tritium content was present as [3H]acetylcholine. Evidence was presented that homoexchange is not or is less involved in choline uptake than in GABA uptake. A kinetic analysis of sodium‐dependent high affinity choline uptake was performed after all treatments. We found changes in Vmax, after all treatments, which were consistently in the same direction as the alterations in activity. The proposal is made that the sodium‐dependent high affinity choline uptake is coupled to cholinergic activity in such a way as to regulate the entry of choline for the maintenance of acetylcholine synthesis. The findings also lead us to propose that sodium‐dependent high affinity choline uptake in vitro be utilized as a rapid, relative measure of the activity of cholinergic nerve terminals in vivo.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

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