Valproic acid and bicuculline affect the formation of glycerolipid in rat brain.

To ascertain the effects of bicuculline and of sodium valproate on the incorporation of glycerol into rat brain lipid, rats were divided into 5 groups: (a) controls; (b) treated with sodium valproate (400 mg/kg body wt); (c) treated with bicuculline (12.5 ?mol/kg body wt); (d) treated with sodium valproate as in (b) + bicuculline as in (c); and (e) treated with bicuculline (25 ?mol/kg body wt). Only rats of group (c) had seizures, which lasted until the end of the experiment. Each animal received 20 ?Ci of [2-(3)H]glycerol by intraventricular route and was sacrificed 12 min afterwards. Hippocampi and cerebella were taken and lipid extracted and separated by chromatography. The type of treatment influenced very much the fate of injected, labeled glycerol. Indeed, total recovered radioactivity increased following either convulsions or the administration of valproate, whereas both treatments decreased the amount of radioactivity incorporated into lipid. These effects were more evident in cerebella than in hippocampi. The distribution of radioactivity among lipid classes (diglyceride, triglyceride and total phospholipid) was also affected by seizures, which decreased the labeling ratio phospholipid/neutral lipid. The distribution of radioactivity among phospholipid classes was influenced by bicuculline (both at convulsant and non-convulsant doses) and these effects were sometimes antagonized by valproate. We conclude that some effects of bicuculline are exerted through the systemic modifications due to seizures and that other effects are probably connected to neuronal hyperfiring. The data reported in this paper are consistent with both mechanisms of action proposed for valproate, i.e. increased membrane permeability and modifications of GABAergic systems.

Neuropsychological correlates of L-deprenyl therapy in idiopathic parkinsonism.

1. Monoaminergic neurotransmitter systems are known to play an important role in neuropsychological functions and they are impaired in dementia of DAT and PD. 2. L-deprenyl is a monoamine-enhancing drug which at low doses selectively inhibits MAO-B, an enzyme whose brain activity has been reported to increase in normal aging and neurodegenerative dementing disorders. 3. The authors studied the effects of L-deprenyl, 10 mg/day, on several cognitive domains in idiopathic parkinsonians without dementia. Ten out-patients, treated with levodopa plus DDI, were tested before receiving L-deprenyl and retested six months after they had been treated with the drug. A control group of ten parkinsonian out-patients treated with only levodopa plus DDI, matched for age, educational level, severity and duration of extrapyramidal disease, was tested by the same neuropsychological battery and retested after a comparable time interval. 4. Statistically significant changes were noted in the verbal and visuospatial learning performances of PD patients treated with the combination of L-deprenyl and levodopa.

Neuropsychological effects of L-deprenyl in Alzheimer's type dementia.

The monoaminergic neurotransmission defect seen in dementia of the Alzheimer type (DAT) is linked to a known increased activity of type B cerebral monoamine oxidases (MAO-Bs). The use of drugs that are able to block this abnormal activity could therefore be useful in the treatment of some cognitive deficits that characterize DAT. Twenty patients with a clinical diagnosis of DAT and with a slight-moderate mental deterioration were treated with 10 mg/day of L-deprenyl, a selective MAO-B inhibitor, according to a double-blind crossover design vs. placebo. Initial treatment (drug or placebo) was randomly assigned. The patients' cognitive functions were evaluated at baseline and then after 3 and 6 months of treatment with drug or placebo. The patients crossed over treatment after 3 months, without a washout interval. The results of the study show the higher and statistically significant effects of L-deprenyl on memory and attention that seem to be due to an improved function of the monoaminergic systems involved in the process of neuronal degeneration.

L-deprenyl therapy improves verbal memory in amnesic Alzheimer patients.

Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type (DAT). DAT is not, however, a homogenous phenomenon inasmuch as two forms are distinguishable: early onset (EO) and late onset (LO). Moreover, focal patterns of neuropsychological deterioration fall into various subgroups. According to our hypothesis, DAT patients, who at the onset of the disease mainly manifest memory disorders, also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways. In a 6-month randomized, double-blind, cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients. Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test. The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills. We suggest that L-deprenyl, through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems, positively influences cognitive functions and behaviour founded on memory efficiency.

The synthesis in vivo of choline and ethanolamine phosphoglycerides in different brain areas during aging.

The biosynthesis of choline and ethanolamine phosphoglycerides was tested in vivo in different brain areas of the rat during aging. Mixtures of [2-3H] glycerol and [Me-14C] choline or [2-3H] glycerol and [2-14C] ethanolamine were injected into lateral ventricle of the brain as lipid precursors and their incorporation into corresponding phospholipid was examined. A significant decrease of synthesis of both phosphoglycerides takes place in cerebral cortex and in the striatum, and is already apparent at 9 months of age with no further decrease or change thereafter. No significant change takes place in the cerebellum. The unchanged absorption of injected water-soluble precursors, together with the lack of any significant change of phospholipid/protein ratio in all examined brain areas, suggests that the incorporation of both glycerol and nitrogen bases are affected by aging.

Individual differences in cerebral organization: influence of sex and familial sinistrality in the language lateralization of strongly right-handed subjects.

Sixty right-handed subjects, divided into four groups of 15 according to sex and familial sinistrality (FS), performed a test of language lateralization. A verbal-manual dual-task paradigm was employed. Results suggest that the pattern of cerebral organization may differ among right-handers in relation to both sex and FS. However, it is not merely the separate influence of these two factors, but rather their interaction which determines the pattern. It is stressed that identification of individual predictors of language laterality may provide some information on prognosis and management of aphasic patients.

[Therapy of insomnia]. / La terapia dell'insonnia.

The authors review the neurochemical and electrophysiological features of insomnia, together with the results obtained by various substances. The literature data show that the benzodiazepines (BZ) should be administered for short periods of time, in order to avoid addiction and withdrawal symptoms. For this reason, the authors suggest that, before starting a therapy with such substances, an accurate clinical evaluation should be made and a good knowledge of the pharmacokinetics of the various BZ is essential.

[Treatment of progressive supranuclear palsy]. / La terapia della paralisi sopranucleare progressiva.

The neuropharmacological and neurochemical features of Progressive Supranuclear Palsy (PSP) are reviewed, together with the results obtained by various therapeutic trials. PSP is a neurodegenerative disease which often causes Parkinsonian symptoms but dopaminomimetic drugs have given rise to poor improvement, in spite of dopamine decrease observed in PSP patients' nigrostriatal region. The uselessness of L-DOPA therapy in PSP patients may explain the numerous failures encountered in PSP patients misdiagnosed as Parkinsonian. On the basis of the recent discovery of striatal dopaminergic receptor abnormalities and of interaction between various neurotransmitters, the authors suggest some possible therapeutic substances that might improve the outcome of the disease.