Clinical Neuroscience

[The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and β-actin genes in rat brain]

KÁLMÁN János, PÁKÁSKI Magdolna, SZŰCS Szabina, KÁLMÁN Sára, FAZEKAS Örsike, SÁNTHA Petra, SZABÓ Gyula, JANKA Zoltán, KÁLMÁN János

NOVEMBER 20, 2012

Clinical Neuroscience - 2012;65(11-12)

[Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer’s disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations - also affecting the metabolism of β-actin - can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], β-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n=16), CIS (n=10), 10 mg/kg sertindole (n=5) and 10 mg/kg sertindole + CIS (n=4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal β-actin (p<0.01), MAPK-1 and APP (p<0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in β-actin, MAPK-1 and APP expression (p<0.05). Ours is the first report about CIS induced β-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.]



Further articles in this publication

Clinical Neuroscience

[Vinpocetin in neurological diseases]

SZAPÁRY László, KÉSMÁRKY Gábor, TÓTH Kálmán, MISNYOVSZKY Melinda, TÓTH Tímea, BALOGH Ágnes, NAGY Krisztián, NÉMETH György, FEHÉR Gergely

[Introduction - Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused territories may be associated with benefitial clinical states. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. Aims - The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. Results - Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheological variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. Summary - Based on the above mentioned results vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.]

Clinical Neuroscience

[Rivaroxaban in prevention of stroke in patients with atrial fibrillation]


[Atrial fibrillation (AF) is well established risk factor for cardioembolic stroke. With thromboprophylatic treatment we can reduce the risk of stroke in patients with AF. Oral vitamin K antagonists (VKA) such as warfarin and acenocoumarol are effective for stroke prevention in patients with atrial fibrillation. VKAs are associated with several limitations including very narrow therapeutic range, several factors (diet, drugs, alcohol consumption) affecting the effect of VKA and excessive bleeding may occur if INR value not controlled successfully. New oral anticoagulant direct Xa factor inhibitor rivaroxaban has a good therapeutic efficacy in prevention (primary and secondary) of stroke in AF patients. Its advantages are including no need for monitoring, fixed oral dose, not affected by meal, age and body weight, all of them can improve patient adherence. In ROCKET AF trial in patients with AF, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group.]

Clinical Neuroscience

[Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis]


[Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsingremitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine- 1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.]

Clinical Neuroscience

[Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part I: Concept of resistance]

VADÁSZ Dávid, SZTRIHA K László, SAS Katalin, VÉCSEI László

[Aspirin and clopidogrel are well established as antiplatelet medication in the treatment of atherothrombotic vascular disease. However, despite treatment, a substantial number of patients experience recurrent ischemic episodes, referred to as aspirin or clopidogrel treatment failure. Various laboratory techniques are available with which to evaluate the effectiveness of antiplatelet drugs. Interestingly, the agreement between the results of the different tests may be poor. The term aspirin or clopidogrel resistance denotes those conditions in which an inadequate inhibitory efficacy of the given antiplatelet agent is detected by an in vitro assay of platelet function. It has been estimated that on average some 30% of patients treated with aspirin, and 20% on clopidogrel, do not achieve an appropriate level of efficacy as concerns platelet activity.]

Clinical Neuroscience

[Clinical experiences with Creutzfeldt-Jakob disease: three case studies]

SZŰCS Anna, VÁRALLYAY Péter, OSZTIE Éva, PAPP Erzsébet, SÓLYOM András, FINTA Lehel, VARGA Dániel, BARCS Gábor, HOLLÓ András, KAMONDI Anita

[The clinical picture, electroencephalographic, imaging and cerebrospinal fluid parameters as well as the molecular background of Creutzfeldt-Jakob disease have been well explored. The diagnostic criteria, offering clinicians a fair chance to identify these patients in vivo, have recently been updated. However, the diagnosis is still a challenge in everyday neurological routine. We report on three of our Creutzfeldt-Jakob patients for calling attention to the classical and the recently defined features of the disease. We conclude that based on the rapidly progressing neuropsychiatric syndrome Creutzfeldt-Jakob disease may be suspected; follow-up EEG may reveal the typical (pseudo)-periodic pattern with progressive deterioration of the background activity. In addition, diffusion-weighted brain MRI imaging (DWI) has high diagnostic value. Detection of 14-3-3 protein in the cerebrospinal fluid supports the in vivo diagnosis.]

All articles in the issue

Related contents

Lege Artis Medicinae

[The effects of angiotensin receptor blockers on the nervous system in hypertension and dementia]


[The renin-angiotensin system (RAS) is one of the most important mechanisms regarding the pathomechanism and treatment of hyprtension. The most of the elements of the RAS are found in the nervous system too. The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ARBs) is based on the inhibition of the RAS. ARBs might have a special role in the central nervous system because they do not decrease the production of angiotensin but inhibit its harmful effects mediated through the AT1 receptor while allowing the stimulation of AT2 receptors with resulting pleiotrophic actions. Hypertension is the most important risk factor for stroke and has a negative effect on cognitive functions. Antihypertensive treatment has an effect on the nervous system; in addition to the consequences of the reduced blood pressure, ARBs might provide additional advantages in stroke and dementia prevention.]

Clinical Neuroscience

[Inclusion body myositis - a rarely recognized disorder]


[Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-β failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.]

Clinical Neuroscience

[The role of β-amyloid and mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease]


[Alzheimer’s disease is the most common form of dementia in mid- and late life. The 7-10% of the population over 65 and the 50-60% of the population over 85 are affected by this disease. On the contrary of its prevalence the pathogenesis of the disease is not well defined and there is no effective neuroprotective therapeutic agent. Three predominant neuropathological features of the Alzheimer’s disease brain are intracellular neurofibrillary tangles consisting mainly of the hyperphosphorylated protein t; the extracellular amyloid deposits (neuritic plaques) consisting of amyloid b peptide; and the extensive neuronal cell loss in the hippocampus and in portions of the cerebral cortex. The possible reason of the extensive neuronal cell loss can be the mitochondrial dysfunction observed in Alzheimer’s disease. Beyond the unclarified pathogenesis the causality of these characteristic neuropathologic phenomena are still unknown. In this study we would like to deal with two actual hypotheses, with the amyloid cascade and with the mitochondrial cascade hypotheses. We try to give an overview of these two hypotheses and to depict their interrelationship.]

Clinical Neuroscience

[The effect of angiotensin receptor blockers in cerebrovascular disorders and dementia: Bonus in addition to the antihypertensive effect]


[Hypertension and dementia are frequent disorders or rather syndromes. Their incidence is growing with advancing age and hypertension is increasing the risk of cognitive impairment too, while treating hypertension (i.e. the use of antihypertensive medications) is decreasing it. In addition, hypertension is the most important risk factor for stroke. The renin-angiotensin system (RAS) has a special role in the development of hypertension and also involved in the pathogenesis of the most frequent dementia form, namely Alzheimer’s disease. The effect of angiotensin convertase inhibitors and angiotensin receptor blockers (ARB) is based on the inhibition of the RAS, but the ARBs do not inhibit angiotensin formation, just blocking its harmful effects on the AT1 receptor, while allowing the activation of AT2 receptors with pleiotropic effects. Preclinical, epidemiological and clinical therapeutic studies suggest this additional effect of ARBs and these are summarized in this review.]

Clinical Neuroscience

[Epidemiology of dementia in Hungary]

ÉRSEK Katalin, KÁRPÁTI Krisztián, KOVÁCS Tibor, CSILLIK Gabriella, GULÁCSI L. Ádám, GULÁCSI László

[Objective - To estimate the epidemiology and the distribution of disease severity of dementia in Hungary, using published data. To estimate the demented population of 2008 and to make a projection for 2050. Methodology - With an outlook for the international professional literature and the available Hungarian information we examine the epidemiology of dementia in Hungary by age-groups and disease severity (according to MMSE categories), then make our estimation for the entire population. Results - Based on the estimation of the number of demented people in Hungary there is a noticeable difference between the domestic and the internationally published data. According to previous Hungarian studies, the number of the demented subjects vary between 530 and 917 thousand patients. Multiplying the elderly age-group’s populations by the global prevalence data it results in 101 thousand of demented patients. Estimation by the domestic published data we remarkably overestimate the presumed value, whereas by using the global prevalence figures we underestimate. Conclusions - There is a strong need for a representative study to obtain exact figures on the prevalence of dementia in Hungary. Getting exact figures of the Hungarian prevalence of dementia it is a strong need an overall representative study. With the lack of it the health and social care systems are not able to prepare for providing the increasing number of patients.]