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Biomedical subjects

A A Mathé

Publications and source records attributed to A A Mathé.

At least 19 recordsLinked to original sources
PubMed1995

Concurrent analysis of neuropeptides and biogenic amines in brain tissue of rats treated with electroconvulsive stimuli.

We developed a method for measuring neuropeptides and monoamines in the same rat brain tissue and applied this method to study the effects of electroconvulsive stimuli (ECS) on these compounds. Rats were treated with repeated ECS or sham ECS. After sacrifice by focused microwave irradiation, brains were dissected and immediately frozen. The tissues were extracted in acetic acid. After lyophilization the samples were reconstituted in phosphate buffer and divided in three fractions: (1) was further purified on a cation-exchange column before catecholamines were measured on a high-performance liquid chromatography (HPLC) system, (2) for measuring serotonin on the HPLC system, (3) for measuring peptide concentrations by specific radioimmunoassays. Confirming our previous findings, ECS significantly increased neuropeptide Y-like immunoreactivity (-LI) in hippocampus and frontal cortex and neurokinin A-LI in the hippocampus, while no changes in substance P- and neurotensin-LI were detected. New findings were a decrease in noradrenaline concentrations in the frontal and occipital cortex and hippocampus, an increase in dopamine concentrations in the frontal and occipital cortex and no serotonin change. In summary, we have developed methods to measure both peptides and monoamines in the same brain tissue specimens, and have shown that ECS leads to changes in both neuropeptides and classical neurotransmitters in distinct brain regions.

Animals↗
PubMed1995

Region-specific effects of chronic lithium administration on neuropeptide Y and somatostatin mRNA expression in the rat brain.

The aim of this study was to examine the effects of 4-week lithium (Li+) food supplementation on neuropeptide mRNA expression in the rat brain. In situ hybridisation was used to determine the effects on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA. Increases in NPY mRNA levels were seen in the hippocampus, layers II-III of the entorhinal cortex, nucleus accumbens shell and in the medial caudate-putamen. Increases in SS mRNA expression were seen in the layers IV-VI of the entorhinal cortex and in the lateral caudate putamen. Thus, Li+ appears to affect discrete populations of NPY and SS mRNA expressing neurons, with possible relevance to beneficial effects of Li+ in affective disorders.

Animals↗
PubMed1995

Chromatographic and immunochemical characterization of rat brain neuropeptide Y-like immunoreactivity (NPY-LI) following repeated electroconvulsive stimuli.

The present work investigates the possible existence of molecular heterogeneity of endogenous neuropeptide Y (NPY) in the rat brain and, if existing, whether it is affected by repeated electroconvulsive stimuli (ECS). Different column chromatographic techniques (gel-permeation chromatography, HPLC, ion-pair reverse-phase HPLC) were used combined with immunochemical methods based on antisera directed towards two different epitopes of NPY (antiserum N1, directed towards the midportion of NPY, and antiserum C1, directed towards the C-terminal end of NPY). Following repeated ECS increased concentrations of NPY were seen in the occipital cortex and hippocampus (P < 0.001) when analyzed by direct radioimmunoassays (RIA). Chromatographic characterization showed that the NPY mainly consisted of intact NPY (1-36) and sulphoxidated form of NPY, no short C-terminal homologues were found. This is of importance since it has been shown that NPY (1-36) has different biological properties compared to C-terminal homologues.

Animals↗
PubMed1995

A pilot Swedish twin study of affective illness including hospital- and population-ascertained subsamples: results of model fitting.

We investigated the heritability of liability to affective illness (AI) in twins ascertained through psychiatric hospitalization for AI from the Swedish Psychiatric Twin Registry and from the general population Swedish Twin Registry. Lifetime diagnoses were assessed by mailed questionnaire containing, in self-report format, DSM-III-R criteria for mania and major depression (MD). Jointly analyzing both subsamples using Mx, and assuming a multifactorial threshold model, the best-fitting twin model using narrow diagnostic criteria suggested that the liability to AI could be explained by additive genetic effects, with an estimated heritability of liability of 64%, and individual-specific environment. Using broad criteria, results were similar except that the estimated broad heritability of liability was higher (83%) and due largely to dominance genetic effects. Fitting sex-dependent models suggested that the same genetic and environmental factors influenced liability to AI in men and women to the same degree, although women had a lower threshold of manifestation. These results suggested that in Sweden, AI is a highly heritable syndrome and family resemblance is due largely or entirely to genetic factors.

Adult↗
PubMed1995

Limbic effects of repeated electroconvulsive stimulation on neuropeptide Y and somatostatin mRNA expression in the rat brain.

The aim of this study was to determine the effect of repeated electroconvulsive stimulation (ECS) on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA in the rat brain. For that purpose, quantitative in situ hybridization histochemistry and RNA blot analysis were used. In the hippocampal formation the prevalence of NPY mRNA positive neurons increased in the hilus of the dentate gyrus and the CA3 while a decrease was seen in layers II-III of the entorhinal cortex. In contrast, SS mRNA was increased in the granule cells of the dentate gyrus and in most neurons of the outer parts of the layer III in the entorhinal cortex with cell bodies of perforant pathway projections to the hippocampal CA1 region. Both NPY and SS mRNA expressing neurons were increased in numerical density in the prefrontal cortex with similar amounts of mRNA in individual NPY positive neurons after the stimulations while SS mRNA levels decreased in hybridization positive neurons. In the striatum the only observed significant effect was an increased prevalence of NPY mRNA positive neurons in the caudal nucleus accumbens. Our results provide an outline of a complex functional anatomy of ECS in the rat brain. This type of investigations contributes to map the neuronal systems involved in the action of ECT used in the treatment of affective and schizophrenic disorders.

Animals↗
PubMed1995

Seasonal mood variation among Japanese residents of Stockholm.

Depressive symptoms estimated by the Beck Depression Inventory (BDI) were examined in winter and summer in a total of 242 Japanese adults staying less than 2 years or longer than 10 years in Stockholm, where the length of daylight changes dramatically throughout the winter and summer seasons. In spite of the difference in the period of residency, both groups of subjects showed more mental and somatic depressive symptoms in the winter than in the summer. Moreover, the winter BDI score of long stayers was significantly higher than that of short stayers. Accordingly, our results suggest that, although seasonal mood variation is essentially produced by a chronobiological factor, Swedish lifestyle to which long stayers have been accustomed also influences the seasonal mood variation.

Acclimatization↗
PubMed1994

Increased concentration of calcitonin gene-related peptide in cerebrospinal fluid of depressed patients. A possible trait marker of major depressive disorder.

Cerebrospinal fluid (CSF) was collected under controlled conditions from subjects suffering from major depression (n = 63) or schizophrenia (n = 28) and from healthy controls (n = 20). Following Sep-pak extraction, calcitonin gene-related peptide immunoreactivity (CGRP-LI) was determined by radioimmunoassay in sample aliquots. CGRP-LI concentrations in CSF were increased in the depressed patients compared to the schizophrenic and control subjects (P < 0.001). No CGRP-LI differences were found between the latter two groups. CGRP-LI did not correlate to any of the technical (e.g. storage conditions) or patient (demographic, biochemical, or clinical) variables investigated. In view of the CGRP's discrete distribution and specific effects in brain and the above results, we hypothesize that increased CSF CGRP-LI might be a trait marker of major depression. Regardless of the mechanisms (altered synthesis/release/metabolism in brain or changed fate in CSF) leading to elevated CSF CGRP-LI, the identification of a possible disease trait marker should contribute to the early diagnosis of major depression and identification of family members at risk and may help in differential diagnosis in other disorders with affective symptomatology.

Adult↗
PubMed1994

Repeated electroconvulsive stimuli: changes in neuropeptide Y, neurotensin and tachykinin concentrations in time.

1. The effects of repeated electroconvulsive stimuli (ECS) on neuropeptide Y (NPY)-, neurokinin A (NKA)-, substance P (SP)- and neurotensin (NT)- like immunoreactivity (-LI) levels in specific rat brain regions were studied in order to establish changes in peptide tissue concentrations in time after the last ECS. 2. The rats were sacrificed 15 minutes, 60 minutes, 1 day, 7 days or 15 days after the sixth sham ECS or ECS, using focused microwave irradiation. 3. Following dissection of the brains, peptides were extracted and measured in extract aliquots by radioimmunoassays. 4. ECS increased NPY-LI in both right and left hippocampus, frontal cortex and occipital cortex at 15 min, 60 min and 1 day after the treatments. Seven days following the last treatment, NPY-LI concentrations were elevated in the left hippocampus and occipital cortex but not in the corresponding right structures. Fifteen days following the last ECS treatment no changes in NPY concentrations were seen. 5. Also NKA-LI was increased in both the right and left hippocampus; the duration of changes was identical to those of NPY-LI. 6. No effects on SP- or NT-LI were found. 7. These results are in line with our hypothesis that one of the ECT's mechanisms of action might involve its effects on NPY and NKA.

Animals↗
PubMed1994

Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium.

The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected.

Adult↗
PubMed1993

Endothelin concentrations in respiration-related structures of the medulla during the perinatal period of the rat.

Endothelin-like immunoreactivity (ET-LI) was quantified in the developing (foetal and postnatal) rat brain stem and cerebellum using radioimmunoassay. The brain stem structures chosen for this study were (a) dorsal medullary region (DMR) including the region of nucleus tractus solitarius where the peripheral chemoreceptor afferents are known to terminate, (b) ventral medullary region (VMR) where the central chemoreceptors are thought to be located and (c) cerebellum (CER), as a control area. Compared to the prenatal period, significantly elevated concentrations of ET-LI were detected in the early postnatal period and thereafter the concentrations decreased: DMR and VMR: in comparison to the prenatal concentrations, a two-fold increase was found on the day of birth which further increased significantly (P < 0.001) on postnatal day 1 only in the region of DMR; CER: low concentrations of ET-LI were found in the early postnatal period which were not significantly different from the prenatal values. No ET-LI could be detected in any of the three regions in the adult rats. The results are discussed in view of the hypothesis that (1) endothelin appears to play an important role in the perinatal period and (2) it is involved in the chemoreceptor pathway.

Animals↗
PubMed1993

In vivo release of somatostatin from rat hippocampus and striatum.

Rats were implanted with microdialysis probes in hippocampi and striata, and somatostatin-like immunoreactivity (SS-LI) was measured in outflows obtained from awake, freely moving animals 48 and 72 h post implantation. SS-LI was measurable in all dialysates under basal conditions; concentrations were stable and within a narrow range, about 3-6 fmol/ml. Cysteamine (300 mg/kg, s.c.) markedly reduced basal SS-LI concentrations in outflows from hippocampus (P < 0.00001). KCl (100 mM, 10 min) or veratridine (50 microM, 10 min) infusion elevated hippocampal SS-LI output by 55 and 106%, respectively (P's < 0.05). EGTA (10 mM) or tetrodotoxin (2 microM) infusion inhibited the SS-LI release elicited by KCl and veratridine, respectively, without affecting the basal SS-LI outflow. Thus, our results demonstrate that SS-LI is released from rat hippocampus and striatum in vivo, and provide evidence that the peptide may be released in hippocampus by both action potential dependent and independent processes.

Animals↗
PubMed1993

A pilot Swedish twin study of affective illness, including hospital- and population-ascertained subsamples.

OBJECTIVE: We sought to compare the probandwise concordance rate (PRC) for affective illness (AI) in monozygotic (MZ) and dizygotic (DZ) twins in samples ascertained through psychiatric hospitalization vs samples from the general population. METHODS: Twins were ascertained through psychiatric hospitalization for AI from the Swedish Psychiatric Twin Registry or as a matched sample from the population-based Swedish Twin Registry. Lifetime diagnoses were based on a mailed questionnaire containing, in self-report format, DSM-III-R criteria for mania and major depression. Returned questionnaires were obtained from 1484 individuals and both members of 486 pairs, of whom 154 were classified as MZ, 326 as DZ, and six of unknown zygosity. RESULTS: No evidence was found for violations of the equal environment assumption. Using either a narrow or broad diagnostic approach, the risk for AI in cotwins of proband twins was independent of the gender, polarity (ie, unipolar vs bipolar) and mode of ascertainment of the affected proband (ie, via hospitalization vs from the general population). Combining both subsamples, PRC for total AI using narrow diagnostic criteria was 48.2% in MZ and 23.4% in DZ twins. Using broad diagnostic criteria, the parallel figures were 69.7% and 34.9%. The risk for bipolar illness was substantially increased in the cotwins of probands with bipolar AI. CONCLUSIONS: Genetic factors play a major role in the etiology of AI in Sweden, as assessed by self-report questionnaire. Heritable factors appear to be equally important in AI as ascertained in clinical and epidemiological samples.

Bipolar Disorder↗
PubMed1993

Sinus node dysfunction during long-term lithium treatment.

BACKGROUND AND OBJECTIVE: Lithium has occasionally been reported to cause symptomatic sinus node bradyarrhythmias. The prevalence and mechanism of these arrhythmias during long-term treatment are unknown. The aims of this study were (a) to evaluate the systemic effects of lithium treatment on cardiac conduction in individuals who were free from cardiovascular disorders; (b) to assess the prevalence of lithium treatment in a group of patients with pacemakers; and (c) to evaluate the interaction between the parasympathetic limb of the autonomous nervous system and the sinus node cells during long-term lithium treatment. PATIENTS AND METHODS: 45 patients who had been treated with lithium for > 12 months were investigated in a long-term electrocardiography study. Only patients without cardiovascular disease, or concomitant chronotropic medication, or metabolic disorders known to cause rhythm disturbances were included. An age-stratified population was used as a reference group. 21 patients also underwent analysis of carotid sinus pressure and sinus cycle length before and after atropine to clarify whether neural mechanisms were involved. The prevalence of lithium treated patients was determined in 650 patients with pacemakers. RESULTS: (a) Signs of moderate sinus node dysfunction (sinus arrest > 1.5 s, minimum heart rate < 50 beats/min) were found in 56% and 78% respectively in the lithium-treated group compared with 30% and 30% respectively in the reference group (p < 0.01). Severe sinus node dysfunction was equally common in both groups. (b) The prevalence of chronic lithium treatment in the pacemaker population was 0.46%. (c) Sinus cycle variations were abnormal in the basal state in three (14%) patients and in 11 (52%) patients after atropine despite signs of intact and normal parasympathetic innervation. CONCLUSIONS: Depressed sinus node function was significantly more common in a lithium-treated population than in an age-stratified reference group. Clinically significant dysfunction, however, was uncommon. The effect of lithium on the sinus node seemed to be intrinsic and was not caused by increased parasympathetic tone.

Aged↗
PubMed1992

Electroconvulsive stimuli and brain peptides: effect of modification of seizure duration on neuropeptide Y, neurokinin A, substance P and neurotensin.

We studied the effects of modification of duration of seizures induced by electroconvulsive stimuli (ECS) on the changes in concentration of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and neurotensin (NT)-like immunoreactivity (-LI) in specific rat brain regions. Rats were divided into groups pretreated with saline, indomethacin, flurbiprofen or diazepam prior to either six sham ECSs or six ECSs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, occipital cortex, striatum, hippocampus, pituitary and hypothalamic sections. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Repeated ECS increased NPY-LI and NKA-LI in the hippocampus and the occipital cortex. No effect on SP-LI or NT-LI was found. Indomethacin and flurbiprofen had no effect on the tonic seizure time following ECS, and they did not affect the ECS-induced alterations of the brain peptides. Diazepam pretreatment decreased the tonic seizure time following ECS in a dose-dependent manner. However, diazepam did not modify the ECS-induced increase in NPY-LI and NKA-LI concentrations. The results firmly establish that ECS leads to specific peptide increases in discrete rat brain regions and raise the possibility that such changes may not entirely be a consequence of seizures per se.

Animals↗
PubMed1992

MK-801 prevents the enhanced behavioural response to apomorphine elicited by repeated electroconvulsive treatment in mice.

Repeated administration of electroconvulsive stimuli (ECS) to mice once daily for a period of 7 days results in an enhanced locomotor response induced by apomorphine (1.0 mg/kg, IP). Pretreatment (30 min) with the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (0.01-1.0 mg/kg IP), suppressed ECS-induced seizure activity in a dose-dependent manner. MK-801 (0.01 and 0.033 mg/kg, IP) given 30 min before each ECS dose-dependently decreased apomorphine-mediated responses. Administration of MK-801 (0.033 mg/kg IP) 30 min after each convulsion had the same effect. These results indicate that MK-801 can abolish the ECS-induced enhancement of dopamine-mediated behaviour possibly by interfering with postictal processes. Thus, NMDA receptors seem to be involved in the behavioural changes and presumably also in the neural adaptations produced by repeated ECS.

Animals↗
PubMed1992

Brain neuropeptides: changes by treatment with the convulsants pentylenetetrazole and bicuculline.

1. The effects of chemically induced convulsions, clinically similar to those elicited by electroconvulsive treatment (ECT), on brain regional distribution of neuropeptide Y-, neurokinin A-, substance P- and neurotensin-like immunoreactivities were studied in the rat. 2. Pentylenetetrazole (PTZ) and bicuculline (BIC) were used to induce grand mal seizures. Rats were divided into three groups receiving one of the following treatments: Saline, PTZ (45 mg/kg) or BIC (1.5 mg/kg). 3. After sacrifice by focused microwave irradiation, brains were dissected, peptides extracted and measured by specific radioimmunoassays. 4. Repeated grand mal convulsions induced by PTZ, in similarity to ECT, markedly increased NPY-LI concentrations in frontal cortex and hippocampus. In contrast to ECT, no changes in NKA- or SP-LI levels were seen. NT-LI was lowered in striatum. 5. Bicuculline effects were more circumscribed: some animals developed grand mal and died while convulsing (peptides not measured), others did not develop generalized seizures and were sacrificed after the fourth treatment. 6. The results demonstrate a similar effect of PTZ and ECT on regional NPY-LI concentrations and raise the possibility that grand mal, regardless of etiology, is necessary for effects on peptides.

Animals↗
PubMed1990

Effect of lithium on tachykinins, calcitonin gene-related peptide, and neuropeptide Y in rat brain.

The effects of lithium on brain regional concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities (-LI) were studied in rat. In the pilot study, rats were divided into three groups that were administered vehicle, or 1 or 4 mEq/kg lithium sulphate, respectively, intraperitoneally once/day for 9 days. In the second experiment, rats were divided into three groups receiving vehicle, or 1 or 2 mEq/kg lithium sulphate, respectively, intraperitoneally twice/day for 9 days. After sacrifice by focused microwave irradiation, brains were dissected, weighed, and frozen. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Marked regional differences (P less than .001) were found for each of the peptides measured. In the pilot study the higher lithium dose, 4 mEq/kg, significantly raised neuropeptide levels. However, animals receiving this dose also showed signs of toxicity. In the second experiment, lithium increased SP-LI concentrations in striatum and hypothalamus (72 and 29%, P's less than .001 and .05). NKA-LI was also elevated in striatum (44%, P less than .01). CGRP-LI, in parallel to SP-LI, was increased in striatum and hypothalamus (58 and 78%, P's less than .05 and .01). In contrast, lithium decreased CGRP-LI in the pituitary gland (56%, P less than .01). NPY-LI was increased in striatum, and frontal and occipital cortex (30, 66, and 60%, respectively; P's less than .01, .01, and .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗