Publications (12)41.65 Total impact
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Article: Extraneuronal toxicity of Alzheimer's β-amyloid peptide: comparative study on vertebrate skeletal muscles.
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ABSTRACT: Alzheimer's β-amyloid peptide (βAP) is known to possess a wide range of toxic effects on neurons in vitro and in vivo; however, there is little information available regarding its impact on other excitable tissues such as skeletal muscles, which, apart from brain cells, are thought to also be targets of βAP. Utilizing the combination of electrophysiology and myography, we investigated whether βAP also impairs the functioning of myocytes in frogs and mice. Although application of βAP in the range of 10(-6) to 10(-8) M induced depolarization of muscle fibers in both species, it impaired contractility in frogs but not in mice, by reducing endplate potential amplitude and increasing the threshold potential. Unchanged contractility in the mouse in the presence of βAP is due to a higher safety factor of neuromuscular transmission in mammals compared with amphibians. Possible clinical implications are discussed.Muscle & Nerve 06/2011; 43(6):872-7. · 2.37 Impact Factor -
Article: The contribution of calcium/calmodulin-dependent protein-kinase II (CaMKII) to short-term plasticity at the neuromuscular junction.
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ABSTRACT: Calcium/calmodulin-dependent protein-kinase II (CaMKII) is a ubiquitous intracellular enzyme, which is implicated in learning and memory mechanisms in the central nervous system, however its contribution to peripheral cholinergic neurotransmission is not well characterized. This study evaluated the impact of CaMKII on the function of frog neuromuscular synapse using electrophysiological recordings. Application of the selective CaMKII inhibitor KN-93 (5 microM) did not significantly alter the parameters of evoked and spontaneous quantal acetylcholine release under low-frequency stimulation (0.03 Hz). KN-93, on the other hand, produced pronounced changes in short-term synaptic plasticity: particularly, KN-93 inhibits the second component of paired-pulse facilitation (interpulse intervals of 100 ms and longer) and strengthens the depression of synaptic transmission under high-frequency stimulation (50 Hz). These results imply that CaMKII plays an important role in presynaptic functions at the frog neuromuscular junction, and potentiates quantal acetylcholine release under high-frequency activity.Brain research bulletin 04/2010; 81(6):613-6. · 2.18 Impact Factor -
Article: Coronary artery bypass surgery provokes Alzheimer's disease-like changes in the cerebrospinal fluid.
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ABSTRACT: Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's type dementia is proposed.Journal of Alzheimer's disease: JAD 01/2010; 21(4):1153-64. · 3.74 Impact Factor -
Article: Alzheimer's beta-amyloid-induced depolarization of skeletal muscle fibers: implications for motor dysfunctions in dementia.
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ABSTRACT: Numerous findings obtained over the last decades suggest that accumulation of beta-amyloid peptide (betaAP) plays the central role in the pathogenesis of Alzheimer's disease. It is well established that betaAP has wide range of toxic effects on neurons in vitro and in vivo, however the influence of betaAP in the periphery and on various other types of excitable tissues, eg. skeletal muscle cells, is almost unknown despite the many non-cognitive and other extra-neuronal symptoms associated with Alzheimer's dementia. Here we utilized conventional electrophysiological technique to investigate the effects and mechanisms of betaAP action on the resting membrane potential of frog skeletal muscle fibers. betaAP in the range of concentrations from 10(-6) to 10(-8)M produced slow, significant, reversible depolarization of muscle fiber membranes. The impact developed and was washed out faster at higher concentrations of betaAP (10(-6)-0(-7)M). The effect of betaAP was completely absent when applied in Na+-free Tris+ solutions. betaAP-mediated depolarization was also prevented by tetrodotoxin (10(-5)M) pre-treatment and rescued by tetrodotoxin after-treatment. These findings suggest that betaAP-induced depolarization of skeletal muscle plasma membranes can significantly disturb the functioning of skeletal muscles and therefore contribute to motor dysfunction observed in Alzheimer's disease and other disorders associated with betaAP accumulation.Cellular Physiology and Biochemistry 02/2009; 23(1-3):109-14. · 2.86 Impact Factor -
Article: Ovalbumin‐induced sensitization affects non‐quantal acetylcholine release from motor nerve terminals and alters contractility of skeletal muscles in mice
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ABSTRACT: Skeletal muscles play key roles in the development of various pathologies, including bronchial asthma and several types of auto-immune disorders, e.g. polymyositis. Since most of these maladies have an immunological/allergic element, this paper is devoted to assessing the impact of immunobiological reorganization on the functional properties of isolated skeletal muscles in mice. A combination of two methods (myography and electrophysiology) was used to evaluate extensor digitorum longus (EDL) and diaphragmatic muscle (DM) in this regard. Conventional myographic technique showed that ovalbumin-induced sensitization (OS) produced different changes in the contractile properties of EDL and DM. The amplitudes of carbachol (CCh)-induced contractions increased in DM but decreased in EDL. Those changes were inversely related to OS-mediated changes of non-quantal acetylcholine (ACh) release intensity within the muscle endplate, as shown by the electrophysiologically measured H-effect. These results clearly show that OS-mediated changes of non-quantal ACh release alter the functional properties of postjunctional ACh receptors and therefore contribute to the disturbance of CCh-induced contractility of skeletal muscles. Other mechanisms of OS-mediated changes of skeletal muscle contractility are also proposed and discussed.Experimental physiology 01/2009; 94(2):264 - 268. · 3.17 Impact Factor -
Article: All-or-nothing type biphasic cytokine production of human lymphocytes after exposure to Alzheimer's beta-amyloid peptide.
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ABSTRACT: Neuro-inflammation, triggered by beta-amyloid peptide, is implicated as one of the primary contributors to Alzheimer's disease (AD) pathogenesis, and several cytokines were identified as key instigating factors. To reveal the inflammatory response of lymphocytes to the neuro-toxic beta-amyloid peptide, we evaluated the release of several cytokines from peripheral blood mononuclear cells with immuno-assays (ELISA). From hyper-acute to chronic effects of beta-amyloid peptide were assessed at a wide range of concentrations. The pro-inflammatory interleukin (IL)-1beta, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and Rantes (acronym for regulated on activation, normal T-cell expressed and secreted) as well as the pleiotropic IL-6 showed a biphasic release pattern over time in both low and high doses of amyloid treatment: after an initial increase, their concentration gradually fell to the baseline. The suppressors IL-4 and IL-10 had a sinus-like secretion panel: an acute increase in their levels turned to a depression and later followed by their over-secretion. Interestingly, beta-amyloid below 10(-8) mol/L produced no effect at all, but any molarity above this threshold caused the very same cytokine secretion pattern, the mark of an all-or-nothing response of beta-amyloid peptide. These results delineate a highly organized pro- and anti-inflammatory response of cells to the neuro-toxic peptide. This is the first study to describe how the beta-amyloid-induced inflammatory processes in Alzheimer's dementia are regulated.Biological psychiatry 09/2008; 64(10):891-5. · 8.93 Impact Factor -
Article: All-or-Nothing Type Biphasic Cytokine Production of Human Lymphocytes After Exposure to Alzheimer's β-Amyloid Peptide
Biological Psychiatry - BIOL PSYCHIAT. 01/2008; 64(10):891-895. -
Article: Modulation of neurotransmitter release by carbon monoxide at the frog neuro-muscular junction.
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ABSTRACT: Carbon monoxide (CO) is an endogenous gaseous messenger, which regulates numerous physiological functions in a wide variety of tissues. Using extracellular microelectrode recording from frog neuro-muscular preparation the mechanisms of exogenous and endogenous CO action on evoked quantal acetyl-choline (Ach) release were studied. It was shown that CO application increases Ach-release in dose-dependent manner without changes in pre-synaptic Na+ and K+ currents. The effect of exogenous CO on Ach-release was decreased by prior application of guanylate cyclase inhibitor ODQ and prevented by application of a cyclic guanylate monophosphate (cGMP) analog 8Br-cGMP. Pre-treatment of the preparation with adenylate cyclase inhibitor MDL-12330A has completely abolished the effect of CO, whereas elevation of intracellular level of cyclic adenosine monophosphate (cAMP) mimicked and eliminated CO action. Application of cGMP-activated phosphodiesterase-2 inhibitor EHNA did not prevent CO action, whereas inhibition of cGMP-inhibited phosphodiesterase-3 by quazinone has partially blocked the effect of CO. Utilizing immuno-histochemical methods CO-producing enzyme heme-oxygenase-2 (HO-2) was shown to be expressed in skeletal muscle fibers, mostly in sub-sarcolemmal region, karyolemma and sarcoplasmic reticulum. Zn-protoporphirin-IX, the selective HO-2 blocker, has depressed Ach-release, suggesting the tonic activating effect of endogenous CO on pre-synaptic function. These results suggest that facilitatory effect of CO on Ach-release is mediated by elevation of intracellular cAMP level due to activation of adenylate cyclase and decrease of cAMP breakdown. As such, endogenous skeletal muscle-derived CO mediates tonic retrograde up-regulation of neuro-transmitter release at the frog neuro-muscular junction.Current Drug Metabolism 03/2007; 8(2):177-84. · 5.11 Impact Factor -
Article: Different effects of ATP on the contractile activity of mice diaphragmatic and skeletal muscles.
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ABSTRACT: Apart from acetyl-choline (Ach), adenosine-5'-trisphosphate (ATP) is thought to play a role in neuromuscular function, however little information is available on its cellular physiology. As such, effects of ATP and adenosine on contractility of mice diaphragmatic and skeletal muscles (m. extensor digitorum longa-MEDL) have been investigated in in vitro experiments. Application of carbacholine (CCh) in vitro in different concentrations led to pronounced muscle contractions, varying from 9.15+/-4.76 to 513.13+/-15.4 mg and from 44.65+/-5.01 to 101.46+/-9.11 mg for diaphragm and MEDL, respectively. Two hundred micromolars of CCh in both muscles caused the contraction with the 65% (diaphragm) to 75% (MEDL) of maximal contraction force-this concentration was thus used in further experiments. It was found that application of ATP (100 microM) increased the force of diaphragmatic contraction caused by CCh (200 microM) from 335.2+/-51.4 mg (n=21) in controls to 426.5+/-47.8 mg (n=10; P<0.05), but decreased the contractions of MEDL of CCh from 76.6+/-6.5mg (n=26) in control to 40.2+/-9.0mg (n=8; P<0.05). Application of adenosine (100 microM) had no effect on CCh-induced contractions of these muscles. Resting membrane potential (MP) measurements using sharp electrodes were done at 10, 20 and 30 min after the application of ATP and adenosine. Diaphragm showed depolarization from 75+/-0.6 down to 63.2+/-1.05, 57.2+/-0.96 and 53.6+/-1.1 mV after 10, 20 and 30 min of exposition, respectively (20 fibers from 4 muscles each, P<0.05 in all three cases). Adenosine showed no effect on diaphragmatic MP. Both agents were ineffective in case of MEDL. The effects of ATP in both tissues were abolished by suramin (100 microM), a P2-receptor antagonist, and chelerythrin (50 microM), a specific protein-kinase C (PKC) inhibitor, but were not affected by 1H-[1,2,4]-oxadiazolo-[4,3-alpha]-quinoxalin-1-one (ODQ, 1 microM), a guanylyl-cyclase inhibitor, or by adenosine-3,5-monophosphothioate (Rp-cAMP, 1 microM), a protein-kinase A (PKA) inhibitor. Besides the action on contractile activity, ATP (100 microM) led to a significant (P<0.001) depolarization of diaphragm muscle fibers from 74.5+/-2.3 down to 64+/-2.1, 58.2+/-2.2 and 54.3+/-2.4 mV after 10, 20 and 30 min of incubation, respectively. Incubation of MEDL with the same ATP concentration showed no significant change of MP. Denervation of the muscles for 28 days led to a decrease of CCh-induced contractions of diaphragm down to 171.1+/-34.5mg (n=11, P<0.05), but increased the contractile force of MEDL up to 723.9+/-82.3mg (n=9, P<0.01). Application of ATP elevated the contractility of denervated diaphragm caused by CCh up to normal values (311.1+/-79.7 mg, n=6, P>0.05 versus control), but did not significantly affect of contractility of MEDL, which became 848.1+/-62.7 mg (n=6). These results show that the effects of ATP on both diaphragmatic and skeletal muscles are mediated through P2Y receptors coupled to chelerytrin-sensitive protein-kinase C.Neurochemistry International 12/2006; 49(8):756-63. · 2.86 Impact Factor -
Article: Paired-pulse facilitation of transmitter release at different levels of extracellular calcium concentration.
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ABSTRACT: High-frequency synaptic activity can cause facilitation of transmitter release due to accumulation of "residual Ca(2+)" at the nerve terminal. However, the mechanism of this phenomenon is still under debate. Here we show that, using extracellular recording from frog cutaneous pectoris muscle, paired-pulse facilitation (PPF) at the frog neuro-muscular junction decays in two or three-exponential manner depending upon the extracellular Ca(2+) concentration ([Ca(2+)](e)). First, second and "early" PPF components are analyzed and described in this study. Considering the dependence of PPF on [Ca(2+)](e), existence of several specific high-affinity intra-terminal Ca(2+)-binding sites that underlie the facilitation of transmitter release at the frog neuro-muscular junction is proposed.Neurochemical Research 09/2006; 31(8):1055-8. · 2.24 Impact Factor -
Article: Evidences for calcium-dependent inactivation of calcium current at the frog motor nerve terminal.
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ABSTRACT: Assessment of calcium-dependent inactivation of calcium current in nerve terminals is not feasible due to technical reasons. Perineural measurement of calcium-flow, however, might be utilized as indirect means to evaluate synaptic currents. Using perineural recording from frog neuromuscular junction, supra-threshold stimuli applied to motor nerve in paired-pulse manner with varying inter-pulse intervals (5-50 ms) are demonstrated in this study to cause paired-pulse depression (PPD) of Ca(2+)-current. PPD of Ca(2+)-flow was reduced at lower extracellular Ca(2+) concentrations, in BAPTA-AM and EGTA-AM treated preparations and after replacing extracellular Ca(2+) with Sr(2+). Using perineural measurement of calcium current as an indirect model to investigate synaptic ionic activity, our findings demonstrate that PPD may be attributed to calcium-dependent inactivation of Ca(2+)-current, which may serve as negative feedback in response to massive Ca(2+) entry to motor nerve terminals. A putative sensor of Ca(2+)-current is also proposed in this study.Brain Research Bulletin 06/2006; 69(6):652-5. · 2.82 Impact Factor -
Article: The influence of hypothermia on P2 receptor-mediated responses of frog skeletal muscle.
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ABSTRACT: The contractile responses of isolated Rana ridibunda frog sartorius muscle contractions evoked by electrical field stimulation (EFS) were studied at three temperature conditions of 17, 22 and 27 degrees C. Temperature-dependent increase of muscle contractility was found. ATP (10-100 microM) concentration dependently inhibited the electrical field stimulation-evoked contractions of sartorius muscle at all three temperatures; this effect was significantly more prominent at a temperature of 17 degrees C than at other two temperatures. Adenosine (100 microM) also caused inhibition of electrical field stimulation-evoked contractions which was statistically identical at all three temperature conditions tested. A P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) reduced the inhibitory effect of ATP at all three temperatures but did not affect inhibitory action of adenosine. In contrast, 8-(p-sulfophenyl)theophylline (8-SPT, 100 microM), a nonselective P1 receptor antagonist, abolished inhibitory effects of adenosine at all three temperature conditions but did not antagonize inhibition caused by ATP. In electrophysiological experiments, ATP (100 microM) and adenosine (100 microM) temperature dependently reduced end-plate currents recorded in sartorius neuromuscular junction by voltage-clamp technique. The inhibitory effects of both agonists were enhanced with the decrease of temperature. 8-SPT (100 microM) abolished the inhibitory effect of adenosine but not ATP on end-plate currents. Suramin (100 microM), a nonselective P2 receptor antagonist, inhibited the action of ATP but not adenosine, while PPADS (10 microM) had no influence on the effects of either ATP or adenosine. It is concluded from this study that the effectiveness of P2 receptor-mediated inhibition of frog skeletal muscle contraction in contrast to that of adenosine is dependent on the temperature conditions.European Journal of Pharmacology 03/2005; 509(2-3):187-93. · 2.52 Impact Factor -
Article: Alzheimer’s β-Amyloid-Induced Depolarization of Skeletal Muscle Fibers: Implications for Motor Dysfunctions in Dementia
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ABSTRACT: Numerous findings obtained over the last decades suggest that accumulation of β-amyloid peptide (βAP) plays the central role in the pathogenesis of Alzheimers disease. It is well established that βAP has wide range of toxic effects on neurons in vitro and in vivo, however the influence of βAP in the periphery and on various other types of excitable tissues, eg. skeletal muscle cells, is almost unknown despite the many non-cognitive and other extra-neuronal symptoms associated with Alzheimers dementia. Here we utilized conventional electrophysiological technique to investigate the effects and mechanisms of βAP action on the resting membrane potential of frog skeletal muscle fibers. βAP in the range of concentrations from 10-6 to 10-8M produced slow, significant, reversible depolarization of muscle fiber membranes. The impact developed and was washed out faster at higher concentrations of βAP (10-6 10-7M). The effect of βAP was completely absent when applied in Na+-free Tris+ solutions. βAP-mediated depolarization was also prevented by tetrodotoxin (10-5M) pre-treatment and rescued by tetrodotoxin after-treatment. These findings suggest that βAP-induced depolarization of skeletal muscle plasma membranes can significantly disturb the functioning of skeletal muscles and therefore contribute to motor dysfunction observed in Alzheimers disease and other disorders associated with βAP accumulation.Cellular Physiology and Biochemistry 08/1970; 23(1-3):109-114. · 2.86 Impact Factor
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Institutions
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1970–2011
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Kazan State Medical University
Kazan’, Respublika Tatarstan, Russia
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2008
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Federal University of Minas Gerais
- Departamento de Bioquímica e Imunologia
Belo Horizonte, Estado de Minas Gerais, Brazil
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