Some studies report reduced levels of the dopamine metabolite HVA in CSF in depression. In the present study including 24 depressed patients and 10 controls, we found significantly increased concentrations of total CSF dopamine in depressed patients. This finding suggests a dysfunction in central dopamine turnover in depression. No differences in CSF levels of noradrenaline or the amine metabolites homovanillic acid and 3-methoxy-4-hydroxy-phenylglycol were seen when comparing depressed patients with controls.

Adult↗

PubMedDate not supplied

5-HT and 5-HIAA in cerebrospinal fluid in depression.

CSF 5-HT and 5-HIAA were measured in endogenously depressed patients (ICD-9) (n = 23) and controls (n = 11). Distribution of sex, age and body height was similar in the two groups. Non-parametric statistics were used. In depressed patients CSF 5-HT concentrations were found to be higher (P less than or equal to 0.01) than in controls. A further classification of the depressed patients by the Newcastle Scale showed that the highest values were found in the endogenous group compared to the non-endogenous group (P less than or equal to 0.02). CSF 5-HIAA was found to be equal in the two groups, even when pairs matched for height were compared. No relation between clinical recovery due to drug treatment and changes in CSF 5-HT was seen. Our data support a possible involvement of 5-HT in the biology of depression, but the anatomical and functional levels of a serotonin derangement are still unknown.

Amitriptyline↗

PubMedDate not supplied

Effects of chronic ethanol exposure on fatty acids of rat brain glycerophospholipids.

The lipid composition was analysed in forebrain subcellular fractions from rats treated with ethanol for three weeks and control rats. Increased proportions of oleic acid and a decrease in palmitic acid were consistently found in total glycerophospholipid fractions after ethanol exposure. The fatty acid compositions of individual phospholipids were also significantly changed. The proportion of docosahexaenoic acid was decreased in brain phosphatidylserine. In contrast to the decrease in the degree of unsaturation in phosphatidylserine, there was an opposite change in phosphatidylcholine wherein the degree of unsaturation was increased. No changes were produced in total cholesterol or phospholipid concentrations. These results point to a high degree of complexity of the mechanisms behind ethanol-induced changes in membrane lipid composition. The decrease in unsaturation in phosphatidylserine is probably an adaptive effect in order to counteract the fluidizing effect of ethanol. There are two possible explanations for the increase in unsaturation in brain phosphatidylcholine. The change may be due to adaptation to other biophysical effects, e.g., expansion of the membrane surface or be secondary to a change in liver lipid metabolism.

Animals↗

PubMedDate not supplied

Ethanol effects on bradykinin-stimulated phosphoinositide hydrolysis in NG 108-15 neuroblastoma-glioma cells.

The effect of short-and long-term ethanol exposure on bradykinin-stimulated hydrolysis of phosphatidylinositol 4.5-bisphosphate (PIP2) was investigated in neuroblastoma X glioma hybrid cells (NG 108-15). Acute exposure of 50-150 mM ethanol neither influenced the bradykinin-stimulated accumulation of [3H]-inositol phosphates (IP1, IP2, IP3) nor the hydrolysis of PIP2 in cells labelled with [3H]-inositol. Furthermore, ethanol (100 mM) added in the absence of agonist did not influence these parameters. However, in cells cultivated for 4 days in 100 mM ethanol, PIP2 hydrolysis and IP1, IP2 and IP3 formation after stimulation by 10(-6)-10(-5) M bradykinin was markedly inhibited while there was no effect on the basal levels or on the levels found after stimulation with low concentrations of bradykinin. The inhibitory effect of ethanol on IP accumulation became significant after 2-3 days of ethanol.

Bradykinin↗

PubMedDate not supplied

Serum fatty acid pattern in chronic alcoholics after acute abuse.

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Adult↗

PubMedDate not supplied

Effects of chronic ethanol treatment on lipid composition and prostaglandins in rats fed essential fatty acid deficient diets.

Rats of the third generation fed on a diet with 0.3 energy-% (low-essential fatty acids (EFA) or 3 energy-% (normal-EFA) essential fatty acids were given once-daily intraperitoneal injections of ethanol 3 g/kg or isocaloric glucose for 23 days. At the end of the experiment, organs were removed and their weight and lipid composition were determined. The postmortem accumulation of the prostaglandins PGE2, PGF2 alpha and 6-keto-PGF1 alpha was used to assess prostaglandin (PG) precursor availability in the organs. Ethanol was found to amplify the biochemical indicators of EFA-deficiency. The fatty acids 20:3 n-9 in brain phosphatidylethanolamine and phosphatidylinositol and 22:5 n-6 in brain phosphatidylethanolamine and phosphatidylserine were significantly higher in the ethanol group compared to the control group. In the kidney, the 20:3 n-9/20:4 n-6 ratio in phosphatidylinositol and phosphatidylserine was significantly higher in the ethanol group compared to the control group. The low-EFA animals had a lower output of urinary PGF2 alpha than the normal EFA animals. Chronic ethanol treatment gave a pronounced increase of urinary PGF2 alpha in both groups. Kidney levels of PGs were lower in the low EFA-animals. Chronic ethanol treatment gave a further decrease in kidney PGs. PG levels were the same in brains from low-EFA and normal-EFA animals with no effects of ethanol. The data are consistent with an increased utilization of EFA during chronic ethanol intoxication leading to a depletion of PG precursor stores in some but not all organs.

Alcoholism↗

PubMedDate not supplied

Brain and plasma proteins in spinal fluid as markers for brain damage and severity of stroke.

Forty well-defined acute stroke patients were investigated for some cerebro-spinal fluid (CSF) markers of cerebral damage. Myelin-basic protein (MBP), tau-fraction, albumin, IgG and transferrin were analyzed on two early occasions after onset of clinical symptoms. Patients with transitory ischaemic attack (TIA) had normal values for MBP both at first and second lumbar puncture. Patients with cerebral infarction and haemorrhage had mean MBP concentrations higher than normal at both lumbar punctures. In cerebral infarction there was a significant increase in MBP from the first to the second lumbar puncture. Patients with intracerebral haemorrhage showed the highest mean MBP values and MBP was markedly elevated already at the first lumbar puncture, suggesting different mechanisms of destruction of nervous tissue in cerebral infarction and bleeding. The amount of MBP was also significantly correlated to the visibility of the cerebral lesion at CT-scan and to the short-term outcome of the patients. The tau-fraction, indicating damage to grey matter, was higher than normal in the majority of patients with cerebral infarction and TIA. The concentration of MBP increases with the extent of brain lesion and a high value indicates a poor short-term prognosis for the patient. This study shows that the brain specific MBP in CSF is a useful marker of cerebral damage in acute cerebrovascular disease.

Acute Disease↗

PubMedDate not supplied

Comparative studies of intracerebroventricularly administered cysteamine and pantethine in different behavioral tests and on brain catecholamines in rats.

In a passive avoidance test, intracerebroventricular administration (post-trial treatment) of the somatostatin-depleting compound cysteamine decreased the avoidance latency of the rats in a dose-related manner, while the effect of pantethine (which is metabolized to cysteamine) was less pronounced. In open-field studies, both compounds decreased the motor activity (ambulation, rearing) of the animals 15 min after the injection followed by a subsequent recuperation of the locomotor depression. Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr). Cysteamine decreased the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid content in the hypothalamus, whereas the effects of pantethine were less expressed. Both compounds slightly decreased the striatal noradrenaline and increased the dihydroxyphenyl acetic acid levels at 15 and 60 min after administration. However, contrary to pantethine, 4 hr after treatment with cysteamine, there was a decrease in dihydroxyphenyl acetic acid concentration in this brain region. These findings suggest that both pantethine and cysteamine attenuate passive avoidance latency after intracerebroventricular treatment. The different efficiency of pantethine and its metabolite cysteamine might be connected to the low pantetheinase activity of the brain tissue; however, some direct effects of pantethine cannot be excluded. The different effects of the two compounds on the open-field activity are possibly associated with the diverse effects of the compounds on the striatal dopaminergic neurotransmission.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Cysteamine and pantethine effects on passive avoidance behavior, shuttle box learning, open-field activity, striatal catecholamines and somatostatin.

The effects of cysteamine and pantethine were compared on different behavioral tests and neurochemical parameters in rats. Cysteamine, administered in high dose (3.90 mM/kg s.c.), decreased the locomotor and rearing activities of rats, while it slightly but not significantly increased the avoidance latency in a passive avoidance test. Pantethine, 24 hr after its administration, significantly increased the dihydroxyphenyl acetic acid (DOPAC) levels in the striatum. Cysteamine slightly reduced the DOPAC level without influencing the catecholamine levels in this brain area. The striatal somatostatin concentration was reduced 24 hr after the administration of cysteamine, while pantethine did not influence it. After repeated daily injections of pantethine, the drug facilitated the shuttle box learning process and increased the intertrial and open-field activities of the animals. Cysteamine only slightly increased the locomotion and rearing and did not influence the shuttle box learning. Both pantethine and cysteamine slowed the rate of the "body weight increase" of the animals when compared to a saline-treated group. These findings suggest that the locomotor activation induced by pantethine 24 hr after its administration plays an important role in its behavioral effects. It might be that the striatal dopaminergic transmission, modified by administration of pantethine, plays some role in the higher locomotor activity induced by the substance.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Effects of pantethine, cysteamine and pantothenic acid on open-field behavior and brain catecholamines in rats.

Cysteamine (1.95 mM/kg) markedly decreased the locomotor, rearing and grooming activities, as well as the number of defecation boluses in an open-field test. An equimolar dose of pantethine reduced the locomotor activity to a lesser extent, but has the same potency in decreasing the number of defecation boluses, whereas pantothenic acid did not affect the behavior of the rats. Cysteamine, and to a lesser extent pantethine, reduced the noradrenaline and increased the dopamine and DOPAC concentrations in the hypothalamus. Pantothenic acid itself did not influence the hypothalamic catecholamine concentrations. These results suggest that the lower efficacy of pantethine compared to cysteamine on both behavioral and neurochemical parameters is probably due to a rate-limiting activity of the enzyme pantetheinase in the conversion of pantetheine to cysteamine.

3,4-Dihydroxyphenylacetic Acid↗