Biomedical subjects

György Bagdy

Publications and source records attributed to György Bagdy.

8 recordsLinked to original sources

PubMed2007

The role of diacylglycerol lipase in constitutive and angiotensin AT1 receptor-stimulated cannabinoid CB1 receptor activity.

The cannabinoid CB1 receptor (CB1R) is a G protein-coupled receptor, which couples to the Gi/o family of heterotrimeric G proteins. The receptor displays both basal and agonist-induced signaling and internalization. Although basal activity of CB1Rs is attributed to constitutive (agonist-independent) receptor activity, studies in neurons suggested a role of postsynaptic endocannabinoid (eCB) release in the persistent activity of presynaptic CB1Rs. To elucidate the role of eCBs in basal CB1R activity, we have investigated the role of diacylglycerol lipase (DAGL) in this process in Chinese hamster ovary (CHO) cells, which are not targeted specifically with eCBs. Agonist-induced G protein activation was determined by detecting dissociation G protein subunits expressed in CHO cells with bioluminescence resonance energy transfer (BRET), after labeling the alpha and beta subunits with Renilla luciferase and enhanced yellow fluorescent protein (EYFP), respectively. Preincubation of the cells with tetrahydrolipstatin (THL), a known inhibitor of DAGLs, caused inhibition of the basal activity of CB1R. Moreover, preincubation of CHO and cultured hippocampal neurons with THL increased the number of CB1Rs on the cell membrane, which reflects its inhibitory action on CB1R internalization in non-simulated cells. In CHO cells co-expressing CB1R and angiotensin AT1 receptors, angiotensin II-induced Go protein activation that was blocked by both a CB1R antagonist and THL. These data indicate that cell-derived eCB mediators have a general role in the basal activity of CB1Rs in non-neural cells and neurons, and that this mechanism can be stimulated by AT1 receptor activation.

Animals↗

PubMed2006

Persistent cerebrovascular effects of MDMA and acute responses to the drug.

Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [(3)H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

Acute Disease↗

PubMed2006

Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: temporal, spatial, and cellular patterns.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") causes long-term disturbance of the serotonergic system. We examined the temporal, spatial, and cellular distribution of three molecular chaperones, Hsp27, Hsp72, and Hsp90, 3 and 7 days after treatment with 7.5, 15, and 30 mg/kg single intraperitoneal (i.p.) doses of MDMA in Dark Agouti rat brains. Furthermore, we compared the immunostaining patterns of molecular chaperones with serotonergic axonal-vulnerability evaluated by tryptophan-hydroxylase (TryOH) immunoreactivity and with astroglial-activation detected by GFAP-immunostaining. There was a marked reduction in TryOH-immunoreactive axon density after MDMA treatment in all examined areas at both time points. Three days after treatment, a significant dose-dependent increase in Hsp27-immunoreactive protoplasmic astrocytes was found in the cingulate, frontal, occipital, and pyriform cortex, and in the hippocampus CA1. However, there was no increase in astroglial Hsp27-immunoreactivity in the caudate putamen, lateral septal nucleus, or anterior hypothalamus. A significant increase in the GFAP immunostaining density of protoplasmic astrocytes was found only in the hippocampus CA1. In addition, numerous strong Hsp72-immunopositive neurons were found in some brain areas only 3 days after treatment with 30 mg/kg MDMA. Increased Hsp27-immunoreactivity exclusively in the examined cortical areas reveals that Hsp27 is a sensitive marker of astroglial response to the effects of MDMA in these regions of Dark Agouti rat brain and suggests differential responses in astroglial Hsp27-expression between distinct brain areas. The co-occurrence of Hsp27 and GFAP response exclusively in the hippocampus CA1 may suggest the particular vulnerability of this region. The presence of strong Hsp72-immunopositive neurons in certain brain areas may reflect additional effects of MDMA on nonserotonergic neurons.

Animals↗

PubMed2005

Subcellular distribution of components of the ubiquitin-proteasome system in non-diseased human and rat brain.

Our aim was to investigate and to compare the intracellular distribution of ubiquitin, 20S proteasome, and all six proteasomal regulatory ATPases in non-diseased human and rat brains. Ubiquitin and ATPases S4 and S7 show dominant nuclear immunostaining, whereas subunits S6a, S6b, and S10b show mainly cytoplasmic immunostaining in both species. However, S8 localization is inconsistent, prevailing nuclear in rat and cytoplasmic in human. In rat brain, small clastosome-like nuclear bodies demonstrate strong ubiquitin, 20S, and S6a immunoreactivity both in neurons and glial cells. Prominent nuclear immunolocalization of members of the ubiquitin-proteasome system provides morphological evidence for function of these proteins in transcription regulation and/or DNA repair.

Adenosine Triphosphatases↗

PubMed2005

[Effect of autogenic training with cognitive and symbol therapy on the treatment of patients with primary headache].

BACKGROUND: Only a minor part of headaches are associated with an organic abnormality in the nervous system. In case of migraine and tension headache, the main provoking factor is psychological stress. Furthermore, these syndromes often occur together with depression and anxiety disorders, and when these comorbid conditions are present headache attacks tend to be more frequent, longer and stronger, causing an increase in the consumption of antimigraine agents, and at the same time increase the consumption of antidepressant and anxiolytic agents. Further to drugs, modified versions of Schultz-type autogenic training is also frequently used for anxiolysis. The aim of our research was to study the effect of the cognitive and symbol therapy enhanced autogenic training on headache and related drug consumption in three different types of primary headaches. METHOD: Twenty five female patients with migraine, tension-type headache or mixed headache participated in an eight-month follow-up study. Headache frequency, analgesic, antimigraine and anxiolytic consumption were measured by means of a headache diary. During the first four months (observation phase) patients became familiar with using the diary, and in the second four months they participated in autogenic training. The data of the second, third and fourth months were considered as baseline data. RESULTS AND CONCLUSION: Our method decreased headache frequency and drug consumption in all three headache groups. This means that the cognitive and symbol therapy enhanced autogenic training is an effective alternative for medications in the treatment of primary headaches.

Adolescent↗

PubMed2004

[Nitroglycerin-induced headaches].

INTRODUCTION: Headache is the most prominent side effect of nitrate therapy. Lack of compliance is usually associated with headache which has a detrimental effect on quality of life. In spite of the high frequency of this adverse effect, the headache characteristics, timing and risk factors are less known. On the other hand, intravenously administered nitroglycerin-induced migraine attack is a common human research model in migraine. AIM OF THE PRESENT STUDY: to evaluate the headaches occurring after administration of therapeutic dose of sublingual nitroglycerin, in migraineurs and controls. METHOD: Twenty-eight female migraine patients without aura and 14 healthy controls received 0.5 mg nitroglycerin. Headache intensity and characteristics have been investigated for 24 hours. RESULTS: two types of headache developed after the nitroglycerin administration: (1) an immediate headache that does not fulfil the criteria for migraine, mild and disappears spontaneously within 1 hour; (2) a typical migraine attack without aura develops several hours after the nitroglycerin administration (mean latency: 250 min), moderate or severe, and warrants antimigraine therapy. The two types of headache developed independently. The nitroglycerin-induced headaches have not been determined solely by the previous migraine diagnosis, although both immediate (p = 0.0045) and typical migraine headache (p = 0.00047) were significantly more frequent among migraineurs compared to controls. Moreover, those control subjects who experienced migraine attacks had predispositions to migraine. Previous results of the authors supported that lower platelet serotonin concentration and higher plasma CGRP concentration, during the headache free period, are risk factors that express greater susceptibility to develop both spontaneous and nitroglycerin-induced migraine attack. CONCLUSION: Authors suggest an accurate exploration of the headache case-history before nitroglycerin treatment. This makes it possible to give proper information to migraine patients and possible migraine patients, and thus suitable treatment can be offered if needed.

Administration, Sublingual↗

PubMed2004

[Neurochemical background of the premenstrual syndrome: the role of the serotonergic system].

Current research focusing on the biological background of premenstrual syndrome suggests that both psychological and physiological factors exert their effect by means of the dysregulation of the serotonergic function. The results of several studies point to a variation in the function of the serotonergic system throughout the cycle, which is related to the plasma concentration of the gonadal steroid hormones. Certain parameters of serotonergic function show different values in the different phases of the cycle. The rise in oestrogen concentration is followed by an increase in the 5HT2A receptor expression in brain areas responsible for mood, emotion, cognition and neuroendocrine regulation. The role of serotonin is further supported by its role in depression, anxiety, aggression as well as the efficiency of serotonergic agents in the treatment of premenstrual syndrome. In our article we review the main theories concerning the biological background of the premenstrual syndrome, and we outline in detail the role of the serotonergic system. We review the research on the relationship between serotonergic function and gonadal steroid levels as well as the latest results concerning the state- and trait-like parameters of the serotonergic system. The studies reviewed provide evidence for the relationship between the gonadal steroid function and the serotonergic system. Further research is necessary in order to determine why the cycle-dependent variation in the function of the serotonergic system leads to the development of premenstrual syndrome only in vulnerable women.

Aggression↗

PubMed1998

Gender difference in m-CPP challenge test in healthy volunteers.

Challenge test with oral m-CPP and placebo were performed in 12 healthy, young volunteers (6 male, 6 female) in a double-blind, placebo-controlled, cross-over study to assess possible gender differences in serotonergic responsivity. Women but not men showed significant prolactin and anxiety increase after administration of 0.25 mg/kg oral m-CPPP. Core temperature increased in both sexes compared to placebo. m-CPP induced significant physical symptoms only in men. Gender differences in serotonergic functions may have clinical significance with regard to differences in rates of some psychiatric disorders between the sexes.

Journal Article↗