Search PubMed⌕ Search

Biomedical subjects

A Lajtha

Publications and source records attributed to A Lajtha.

At least 109 records · Page 6Linked to original sources
PubMed1990

Changes with aging in the levels of amino acids in rat CNS structural elements: III. Large neutral amino acids.

This paper reports the concentrations of valine, leucine, isoleucine, phenylalanine, and tyrosine as determined in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected by the punch technique. The levels of other amino acids in the same areas are reported in other papers of this series. The essential amino acids reported in this paper showed great regional heterogeneity, with concentrations in areas of the highest content being 9 to 12 times higher than levels in areas of the lowest content. The relative distributions of these amino acids were fairly similar in that in a number of areas the amino acids were all at very high levels and in some other areas they were all at low levels, with a few exceptions. With aging, levels of some amino acids increased and levels of some others did not change, but the predominant change was a significant decrease in levels with age. The results indicate high regional heterogeneity in amino acid levels and in the changes of these levels with age.

Aging↗
PubMed1990

Changes with aging in the levels of amino acids in rat CNS structural elements: IV. Methionine and basic amino acids.

This paper reports the distribution of methionine, histidine, lysine, arginine, and ornithine in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected by the punch technique. Like that of the other amino acids were reported in previous papers of this series, the distribution of methionine and the basic amino acids was regionally highly heterogeneous. The ratios of levels in the areas of highest concentrations to levels in the areas of lowest concentration varied from 10 to 15 for these amino acids, except that it was 23 for arginine. This heterogeneity is also illustrated by the finding that in some areas arginine was more than 5% of the total amino acid content and in others was less than 0.5%. The distribution of methionine differed from that of the basic amino acids, which were high in hypothalamic areas and low in the limbic system. With aging, methionine and basic amino acids, like the other amino acids studied in this series, mainly decreased in level, although in a few cases increases could be seen. Significant decreases were noted more than five times as often as increases.

Aging↗
PubMed1990

Calpain II activity and calpastatin content in brain regions of 3- and 24-month-old rats.

In previous studies, we found a significantly higher (100% or more) content of cathepsin D in the aging brain. In the present study, we determined activity of Ca2(+)-activated neutral protease requiring millimolar Ca2+ (calpain II, CANP II) and amount of its endogenous inhibitor, calpastatin, in extracts of various brain regions of 3-month-old and 24-month-old male Fischer-344 rats. Calpain II was separated from calpastatin in a single step (chromatography) and its activity was tested using as substrates [methyl-14C]alpha-casein, the cytoskeletal proteins desmin and actin, and a mixture of neurofilament triplet proteins and glial fibrillary acidic proteins (GFAP). We found no changes in calpain II activity in pons-medulla and spinal cord, but significant increases were detected in cortex (72%) and striatum (63%) of the 24-month-old rats using [methyl-14C]alpha-casein as substrate. The profile of desmin and actin breakdown showed regional variations somewhat different from those of [methyl-14C]alpha-casein. With desmin, the greatest increases with age were in the striatum (82%) and hypothalamus (46%), but there were no alterations in cortex, cerebellum, and pons-medulla. With actin, slightly enhanced activity in cortex and cerebellum was noticeable. Calpastatin content in brain regions was also increased, with the regional pattern of increase fairly similar to the pattern of enzyme activity increase. The causes and the physiological consequences of increased calpain and calpastatin content in the aged brain are being investigated. That changes with age are somewhat different with the various brain protein substrates indicates that some of the properties of the enzyme also undergo alteration with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1990

Cellular localization of puromycin-sensitive aminopeptidase isozymes.

We developed monoclonal antibodies (mAbs) against two isozymes of a cytosolic puromycin-sensitive aminopeptidase (PSA-I and PSA-II) purified from chicken brain. The isozymes could be distinguished using Ouchterlony double-immunodiffusion and Western immunoblot. Their distribution in neuronal and glial cells as visualized by indirect immunofluorescence with these mAbs was found to differ: PSA-I was confined mostly to glial lysosomes; PSA-II showed fibrillar distribution in both types of nerve cells, but in disparate patterns. These results and our findings of peptide structural differences suggest that the two PSA isozymes are expressed differently in the nervous system.

Aminopeptidases↗
PubMed1990

Effects of social isolation and the time of day on testosterone levels in plasma of C57BL/6By and BALB/cBy mice.

Adult male C57BL/6By and BALB/cBy mice were housed either in large groups (20 per cage) or individually, and levels of plasma testosterone were measured in samples taken in the morning (9 to 10 A.M.) and in the evening (9 to 10 P.M.). No significant strain differences were found in testosterone levels, but the mean testis weight was significantly higher in the BALB/cBy strain. Two-way analysis of variances of pooled plasma testosterone data showed that social isolation of males results in a significant increase in A.M. (but not P.M.) testosterone concentrations and increased testis weight in both strains. Our results suggest that differential housing of a social species can affect testicular function. Since testicular function can also be influenced by the time of day, the question is raised whether the expression of circadian variation in plasma testosterone level is dependent on population density.

Animals↗
PubMed1990

Spike-and-wave neocortical patterns in rats: genetic and aminergic control.

Spontaneously occurring and drug-induced high voltage spike-and-wave electroencephalogram patterns were examined in inbred rats of the Fischer 344 and Buffalo strains and of the random-bred Sprague-Dawley strain at different ages. In addition, tyrosine hydroxylase activity and dopamine D2 receptor density were determined in the substantia nigra, corpus striatum, olfactory tubercle and ponsmedulla areas of Fisher 344 and Buffalo animals. High voltage spike-and-wave episodes were present in 87.5% of the 3-month-old and in 100% of the older Fischer 344 rats. High voltage spike-and-wave episodes were completely absent in 3-month-old Buffalo and Sprague-Dawley animals but could be induced by systemic injection of pentylenetetrazol and at an older age they appeared in 58.3% (12-month) and 71.4% (greater than 26-month) of the subjects of these strains. The incidence and duration of high voltage spike-and-wave episodes were significantly higher/longer in Fischer 344 rats than in the age-matched Buffalo and Sprague-Dawley animals. The dopamine blocker acepromazine induced a several-fold increase of the incidence and duration of high voltage spike-and-wave episodes in 3-month-old Fischer 344 rats, but failed to induce high voltage spike-and-wave episodes in Buffalo animals at this age. However, acepromazine also triggered high voltage spike-and-wave episodes in Buffalo rats when they were pretreated with subthreshold doses of pentylenetetrazol. Tyrosine hydroxylase activity was significantly higher in the substantia nigra, corpus striatum and olfactory tubercle of the Fischer 344 strain than in Buffalo rats. The higher tyrosine hydroxylase activity was paralleled with significantly higher D2 binding values in the corpus striatum and olfactory tubercle of Fischer 344 rats. These findings suggest that the neocortical high voltage spike-and-wave phenotype is genetically mediated and that the inbred Fischer 344 and Buffalo rats with defined bilineal origin will facilitate future works aimed at the identification of genetic elements involved in the generation of neocortical high voltage spike-and-wave episodes. The significant genotype x age interaction supports the suggestion, however, that high voltage spike-and-wave episodes are likely to be influenced by more than one gene; some of them are probably related to the regulation of brain aminergic systems.

Aging↗
PubMed1989

The effect of nicotine on catecholaminergic storage vesicles.

The present study examined the action of nicotine on the accumulation of [3H]dopamine into synaptic vesicles prepared from mouse cerebral cortex or bovine striatum. Nicotine was shown to be a weak inhibitor of [3H]dopamine accumulation, with an IC50 of approximately 0.2-0.4 mM. In addition, repeated nicotine administration (1.2 mg (-)-nicotine di-(+)tartrate/kg s.c., twice daily for 10 days) in vivo in BALB/cBy male mice did not alter the potency of reserpine in inhibiting [3H]dopamine accumulation into synaptic vesicles, nor did it change the slight shift induced by nicotine in the potency of reserpine in inhibiting [3H]dopamine accumulation. The present results show that nicotine is an inhibitor of vesicular dopamine accumulation at high concentrations.

Animals↗
PubMed1989

Evidence for a common site of action of lidocaine and carbamazepine in voltage-dependent sodium channels.

The finding that the development of lidocaine-kindled seizures is blocked by carbamazepine suggests an interaction of carbamazepine with local anesthetic mechanisms. To study the site of interaction, the effects of lidocaine, carbamazepine and another anticonvulsant drug, phenytoin on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate to the sodium channel gating complex were examined in vitro in a rat brain hippocampus preparation. Lidocaine shifted the concentration inhibition curve of carbamazepine to the right and vice versa. Carbamazepine shifted the concentration inhibition curve of phenytoin to the right and vice versa. The experimentally determined apparent dissociation constants were in a good agreement with the dissociation constants calculated for a one-site model, suggesting that the interaction occurs because lidocaine shares a common binding site with carbamazepine and phenytoin in the voltage-dependent sodium channels.

Animals↗
PubMed1989

Metaphit, an isothiocyanate analog of PCP, induces audiogenic seizures in mice.

Metaphit induces audiogenic seizures in mice. The most severe clonic/tonic seizures occur 18-24 h after metaphit administration. After 48 h the incidence of the seizure episodes begin to diminish. These audiogenic seizures can be prevented by the administration of either PCP or MK-801 24 h after metaphit and 30 min prior to audio stimulation. These seizures may be due to a modulation of the PCP recognition site by metaphit which results in an enhanced probability that the NMDA/PCP ion channels are open.

Acoustic Stimulation↗
PubMed1989

Chronic L-deprenyl-induced up-regulation of the dopamine uptake carrier.

L-Deprenyl is an inhibitor of monoamine oxidase B and dopamine uptake. Chronic L-deprenyl (10 mg/kg i.p., twice weekly for 4 weeks) was shown to inhibit monoamine oxidase B activity by 89%, and also to induce an up-regulation of the [3H]mazindol binding site associated with the striatal dopamine uptake carrier. Scatchard analysis indicated a 56% increase in the maximal number of [3H]mazindol binding sites in chronic L-deprenyl animals, but no effect on the affinity of these binding sites. The ability of L-deprenyl to up-regulate the [3H]mazindol-associated dopamine uptake carrier appears to be a result of its role as a dopamine uptake inhibitor.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Action of nicotine on accumbens dopamine and attenuation with repeated administration.

The behavioral and physiological effects of repeated nicotine administration are complex; sedation and hypothermia are present early but become attenuated while locomotor activity increases. Maximal blood levels and behavioral changes occur within 10 min of s.c. injection. We examined the effects of 10 nicotine injections (0.8 mg/kg) in 14 days on the levels of brain amines following challenge with either saline or nicotine on the 15th day. Dopamine, DOPAC, HVA, 3-methoxytyramine, norepinephrine, 5-hydroxytyramine, and 5-HIAA were measured in the frontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen, substantia nigra and ventral tegmental area. Ten minutes after nicotine was given to rats that had previously received only saline the levels of dopamine and its metabolite DOPAC indicated an increase in dopamine turnover in the nucleus accumbens. Of the areas examined the accumbens was the most sensitive to nicotine, with few significant amine changes in other regions. Twenty-four hours after the last nicotine injection the levels of dopamine and its metabolites indicated a sustained decrease in dopamine turnover in the accumbens induced by repeated administration. Following repeated nicotine a nicotine challenge still induced an acute increase in dopamine turnover in the accumbens, but the response was less than in animals not previously given nicotine. The results confirm earlier studies indicating that the accumbens is a major site of nicotine action.

Animals↗
PubMed1989

Evidence for the involvement of Na+/Ca2+ exchange in the stimulation of inositol phospholipid hydrolysis by sodium channel activation and depolarization.

Amiloride, an inhibitor of the Na+/Ca2+ exchanger, blocked the hydrolysis of inositol phospholipids in mouse cerebrocortical slices induced by the sodium channel activator veratridine, by KCl, or by the sodium ionophore monensin; there was no inhibition by A 23187, a Ca2+ ionophore, or by serotonin. It is concluded that agents that increase intracellular Na2+ stimulate inositide hydrolysis by an indirect effect via Na+/Ca2+ exchange.

Amiloride↗
PubMed1989

A high performance liquid chromatography/electrochemical assay for glutamatergic neurotransmitters in the rat brain.

The release and content of the excitatory amino acid neurotransmitters glutamate and aspartate in rat striatum were determined by liquid chromatography/electrochemistry. This determination was based on precolumn off-line derivatization of the amino acids with o-phthaldialdehyde and 2-mercaptoethanol (OPT/2-MCE), and the adducts formed were separated under isocratic conditions and oxidized on a glassy carbon electrode at moderate potential (+0.6 V). The standard and the extracted glutamate when derivatized with OPT/2-MCE produced similar electrochemical and chromatographic characteristics. The detection limit of glutamate was 0.5 pmol. Depolarization induced by the high potassium medium (40 mmol/L) enhanced the release of glutamate and aspartate from superfused rat striatum, whereas the efflux of glutamine remained unchanged. Perfusion (for 60-70 min) removed 50-80% of the free amino acid content of striatal tissue. The method described here is useful in neurochemical investigations of the brain amino acid neurotransmitters.

Animals↗
PubMed1989

Effect of cocaine and cocaine congeners on veratridine-induced depolarization in mouse cerebrocortical synaptoneurosomes.

Structure-activity relationships were determined for cocaine congeners in counteracting the depolarization induced by the action of veratridine on voltage-dependent sodium channels of synaptoneurosomes from mouse brain cortex, and their potency was compared to those determined previously on Na+ uptake and batrachotoxinin binding. Cocaine, norcocaine, (+)-pseudococaine, (-)-pseudococaine, (+)-neopseudococaine, benzoyltropine, benzoylpseudotropine, ecgonine methylester, atropine, WIN-35,428, WIN-35,140, WIN-35,065-3, WIN-35,004, and procaine were tested for their potency in inhibiting depolarization as measured by the distribution of the lypophilic cation [3H]triphenylmethylphosphonium across the membrane. All of the tested compounds inhibited the veratridine-induced depolarization in a competitive manner. The structure-activity relationships were similar to those for inhibition of 22Na+ uptake in mouse brain homogenates, and the potency of these local anesthetics in inhibiting veratridine-induced uptake of [3H]triphenylmethylphosphonium correlated well with their potency in inhibiting [3H]batrachotoxinin A 20-alpha-benzoate binding in mouse brain synaptosomes.

Anesthetics, Local↗