Publications by authors named "Maria Rychkova"

13 Publications

  • Page 1 of 1

Psychiatric and cognitive characteristics of older adults admitted to a Video-EEG monitoring (VEM) unit.

Epilepsy Behav 2021 Jul 9;120:107987. Epub 2021 May 9.

Department of Medicine (RMH), The University of Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Parkville, Australia; Melbourne School of Psychological Sciences, The University of Melbourne, Australia.

Objective: To compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit.

Method: This was a retrospective case-control study involving patients admitted for VEM over a two-year period (from April 2018 to April 2020) at two comprehensive epilepsy units. Patients were categorized into an older (≥60 years) and a younger (<60 years) group. Younger patients were individually matched to older adults to form a matched younger group. Diagnosis was determined by a consensus opinion of epileptologists, neurologists, and neuropsychiatrists. The main diagnostic categories were epilepsy, psychogenic nonepileptic seizures (PNES), and 'other' diagnosis (non-diagnostic and other nonepileptic diagnoses). Clinical psychiatric diagnoses were obtained from neuropsychiatric reports. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Subjective cognitive function was assessed using the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) cognitive subscales.

Results: Five-hundred and thirty three patients (71 older, 462 younger) aged 16-91 years were admitted to the VEM unit during the study period. There was a diagnosis of focal epilepsy in 55% of the older group and 48% of the younger group, generalized epilepsy in 3% of the older group and 10% of the younger group, and 'other' in 32% of the older group and 19% of the younger group. Ten percent (2 males and 5 females) of the older group were diagnosed with PNES compared to 22% of the younger group (p = 0.016). A depressive disorder was diagnosed in 34% of the older group and 24% of the younger group (p = 0.20). An anxiety disorder was diagnosed in 15% of the older group and 25% of the younger group (p = 0.15). Mild neurocognitive disorder was more common in the older group (34%) compared to the matched younger group (34% vs 3%, p < 0.001). The older group had lower mean NUCOG scores compared to the matched younger group (79.49 vs 87.73, p = <0.001). There was no evidence for a relationship between mean NUCOG score and overall subjective cognitive difficulties for the older group (r = 0.03, p = 0.83). Among older adults, those diagnosed with PNES had more experiences of childhood trauma. Measures of dissociation, depression, or general anxiety did not differ between PNES and non-PNES diagnoses in the older group.

Conclusion: Psychiatric comorbidities are common among older adults admitted for VEM. The psychological impact of epilepsy and risk factors for PNES seen in younger patients are also applicable in the older group. The older group demonstrated more cognitive impairments than the younger group, although these were usually unrecognized by individuals. Older adults admitted to VEM will benefit from psychiatric and neuropsychological input to ensure a comprehensive care approach to evaluation and management.
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http://dx.doi.org/10.1016/j.yebeh.2021.107987DOI Listing
July 2021

Clinical predictors of discordance between screening tests and psychiatric assessment for depressive and anxiety disorders among patients being evaluated for seizure disorders.

Epilepsia 2021 May 18;62(5):1170-1183. Epub 2021 Mar 18.

Department of Neurology, Alfred Health, Prahran, Victoria, Australia.

Objective: This study was undertaken to identify factors that predict discordance between the screening instruments Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Generalized Anxiety Disorder scale (GAD-7), and diagnoses made by qualified psychiatrists among patients with seizure disorders. Importantly, this is not a validation study; rather, it investigates clinicodemographic predictors of discordance between screening tests and psychiatric assessment.

Methods: Adult patients admitted for inpatient video-electroencephalographic monitoring completed eight psychometric instruments, including the NDDI-E and GAD-7, and psychiatric assessment. Patients were grouped according to agreement between the screening instrument and psychiatrists' diagnoses. Screening was "discordant" if the outcome differed from the psychiatrist's diagnosis, including both false positive and false negative results. Bayesian statistical analyses were used to identify factors associated with discordance.

Results: A total of 411 patients met inclusion criteria; mean age was 39.6 years, and 55.5% (n = 228) were female. Depression screening was discordant in 33% of cases (n = 136/411), driven by false positives (n = 76/136, 56%) rather than false negatives (n = 60/136, 44%). Likewise, anxiety screening was discordant in one third of cases (n = 121/411, 29%) due to false positives (n = 60/121, 50%) and false negatives (n = 61/121, 50%). Seven clinical factors were predictive of discordant screening for both depression and anxiety: greater dissociative symptoms, greater patient-reported adverse events, subjective cognitive impairment, negative affect, detachment, disinhibition, and psychoticism. When the analyses were restricted to only patients with psychogenic nonepileptic seizures (PNES) or epilepsy, the rate of discordant depression screening was higher in the PNES group (n = 29, 47%) compared to the epilepsy group (n = 70, 30%, Bayes factor for the alternative hypothesis = 4.65).

Significance: Patients with seizure disorders who self-report a variety of psychiatric and other symptoms should be evaluated more thoroughly for depression and anxiety, regardless of screening test results, especially if they have PNES and not epilepsy. Clinical assessment by a qualified psychiatrist remains essential in diagnosing depressive and anxiety disorders among such patients.
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http://dx.doi.org/10.1111/epi.16871DOI Listing
May 2021

Short- and long-term outcomes of immediate and delayed treatment in epilepsy diagnosed after one or multiple seizures.

Epilepsy Behav 2021 04 9;117:107880. Epub 2021 Mar 9.

Department of Neurosciences, Central Clinical School, Monash University, Alfred Hospital, The Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC 3050, Australia; School of Public Health and Preventive Medicine, Monash University, 533 St Kilda Road, Melbourne, VIC 3004, Australia. Electronic address:

Objectives: To compare the outcomes between immediate and deferred treatments in patients diagnosed after one or multiple (two or more) seizures.

Methods: Our observational study investigated seizure recurrence and 12-month seizure remission in patients with newly diagnosed epilepsy, comparing immediate to deferred treatment in patients diagnosed after one seizure or after two or more seizures.

Results: Of 598 patients (62% male, median age 39 years), 347 (58%) were treated at diagnosis and 251 (42%) received deferred or no treatment. Seizure recurrence was higher with deferred treatment both in patients diagnosed after two or more seizures (n = 363; adjusted hazard ratio [aHR] = 2.38, 95% confidence interval [CI]: 1.79-3.14, p < 0.001) and after one seizure (n = 235; aHR = 1.41, 95% CI: 0.995-1.99, p = 0.05). Cumulative seizure recurrence rates at two years in patients diagnosed after two or more seizures were 73% with deferred treatment and 49% with immediate treatment (risk-factor-corrected number-needed-to-treat [NNT] = 4), and in those diagnosed after one seizure the rates were 60% and 51% (NNT = 8). Of 380 patients with eligible follow-up (median 4.3 years), 287 (76%) had been in seizure remission for at least one year and 211 (56%) remained in remission at last follow-up. Long-term remission rates were similar between immediate and deferred treatments, and between patients diagnosed after one seizure and those with two or more seizures.

Significance: Immediate rather than deferred treatment was less likely to influence seizure recurrence in patients diagnosed with epilepsy after a single seizure than in those diagnosed after two or more seizures, and showed no differences in long-term seizure freedom.
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http://dx.doi.org/10.1016/j.yebeh.2021.107880DOI Listing
April 2021

Adverse events related to antiepileptic drugs.

Epilepsy Behav 2021 02 22;115:107657. Epub 2020 Dec 22.

Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia; Department of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH), The University of Melbourne, Parkville, Australia.

Objective: Adverse events (AEs) related to antiepileptic drugs (AEDs) may interfere with adequate dosing and patient adherence, leading to suboptimal seizure control, and relatedly, increased injuries, hospitalizations, and mortality. This study investigated the clinicodemographic factors associated with AEs related to AEDs as reported by the Liverpool Adverse Events Profile (LAEP), and explored the ability of LAEP to discriminate between epilepsy and psychogenic nonepileptic seizures (PNES). We hypothesized that female sex, mood disorders, AED-polytherapy, duration, and severity of epilepsy are associated with increased endorsement of AEs related to AEDs, and that endorsement of AEs related to AEDs would significantly differ between epilepsy and PNES patients.

Methods: We prospectively enrolled adult patients admitted to two inpatient video-electroencephalogram monitoring units. Clinicodemographic variables and psychometric measures of depression, anxiety, and cognitive function were recorded. Patient-reported AE endorsement was obtained using the LAEP, which was reduced to four latent domains using exploratory structural equation modeling. General linear models identified variables associated with each domain. Logistic regression determined the ability of LAEP scores to differentiate between epilepsy and PNES.

Results: 311 patients met inclusion criteria. Mean age was 38 years and 56% of patients were female. Network analysis demonstrated strong relationships between depression and anxiety with physical, sleep, psychiatric, and dermatological AE endorsement. Depression, female sex, and AED polytherapy were associated with greater AE endorsement. Epilepsy, compared to PNES, was associated with lower AE endorsement. Fewer prescribed AEDs and greater reported physical AE endorsement were associated with PNES diagnosis.

Significance: There is a strong relationship between patient-reported AEs and psychiatric symptomatology. Those with PNES paradoxically endorse greater physical AEs despite receiving fewer AEDs. Patients who endorse AEs in clinical practice should be screened for comorbid depression or anxiety and treated accordingly.
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http://dx.doi.org/10.1016/j.yebeh.2020.107657DOI Listing
February 2021

Development and validation of a screening questionnaire for psychogenic nonepileptic seizures.

Epilepsy Behav 2020 11 28;112:107482. Epub 2020 Sep 28.

The Epilepsy Unit, Alfred Health, Melbourne, Australia; Department of Neurology, The Royal Melbourne Hospital, Melbourne, Australia; Clinical Outcomes Research Unit (CORe), Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Australia; Department of Medicine (The Royal Melbourne Hospital), The University of Melbourne, Australia; Melbourne School of Psychological Sciences, The University of Melbourne, Australia.

Objective: Epilepsy and psychogenic nonepileptic seizures (PNES) are serious conditions, associated with substantial morbidity and mortality. Although prompt diagnosis is essential, these conditions are frequently misdiagnosed, delaying appropriate treatment. We developed and validated the Anxiety, Abuse, and Somatization Questionnaire (AASQ), a quick and clinically practical tool to differentiate PNES from epilepsy.

Method: We retrospectively identified psychological variables that differentiated epilepsy from PNES in a discovery cohort of patients admitted to a video-electroencephalography monitoring (VEM) unit from 2002 to 2017. From these findings, we developed the AASQ and prospectively validated it in an independent cohort of patients with gold-standard VEM diagnosis.

Results: One thousand two hundred ninety-one patients were included in the retrospective study; mean age was 39.5 years (range: 18-99), 58% were female, 67% had epilepsy, and 33% had PNES. Psychometric data for 192 instrument items were reviewed, receiver operating characteristic curves were computed, and a 20-item AASQ was created. Prospective validation in 74 patients showed that a one-point increase in the AASQ score was associated with 11 times increase in the odds of having PNES compared with epilepsy. Low scores on the AASQ were associated with a low probability of PNES with a negative predictive value of 95%.

Significance: The AASQ is quick, inexpensive, and clinically useful for workup of seizure disorders. The AASQ excludes PNES with a high degree of confidence and can predict PNES with significance when combined with basic clinicodemographic variables. Future research will investigate diagnostic performance of the AASQ in relevant clinical subgroups, such as patients with comorbid epilepsy and PNES.
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http://dx.doi.org/10.1016/j.yebeh.2020.107482DOI Listing
November 2020

The costs of epilepsy in Australia: A productivity-based analysis.

Neurology 2020 12 15;95(24):e3221-e3231. Epub 2020 Sep 15.

From the Department of Neuroscience, Central Clinical School (E.F., Z.C., M.R., T.J.O., P.K.), and School of Public Health and Preventive Medicine (Z.C., E.Z., D.L., P.K., Z.A.), Monash University, Melbourne; Department of Neurology (E.F., M.R., T.J.O., P.K.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., M.R., T.J.O., P.K.), Alfred Health, Melbourne; Department of Medicine (Z.C., M.R., T.J.O., D.L., G.D.J., P.K.), The University of Melbourne, Parkville; Department of Medicine (P.C.), Monash University; Eastern Health (P.C.), Florey Institute of Neuroscience and Mental Health (P.C., G.D.J.), Melbourne; and Department of Neurology (G.D.J.), Austin Hospital, Heidelberg, Australia.

Objective: To determine the health economic burden of epilepsy for Australians of working age by using life table modeling and to model whether improved seizure control may result in substantial health economic benefits.

Methods: Life table modeling was used for working age Australians aged 15-69 years with epilepsy and the cohort was followed until age 70 years. Published 2017 population and epilepsy-related data regarding epilepsy prevalence, mortality, and productivity were used. This model was then re-simulated, assuming the cohort no longer had epilepsy. Differences in outcomes between these cohorts were attributed to epilepsy. Scenarios were also simulated in which the proportion of seizure-free patients increased from baseline 70% up to 75% and 80%.

Results: In 2017, Australians of working age with epilepsy followed until age 70 years were predicted to experience over 14,000 excess deaths, more than 78,000 years of life lost, and over 146,000 productivity-adjusted life years lost due to epilepsy. This resulted in lost gross domestic product (GDP) of US $22.1 billion. Increasing seizure freedom by 5% and 10% would reduce health care costs, save years of life, and translate to US $2.6 billion and US $5.3 billion GDP retained for seizure freedom rates of 75% and 80%, respectively.

Conclusions: Our study highlights the considerable societal and economic burden of epilepsy. Relatively modest improvements in overall seizure control could bring substantial economic benefits.
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http://dx.doi.org/10.1212/WNL.0000000000010862DOI Listing
December 2020

Treatment initiation decisions in newly diagnosed epilepsy-A longitudinal cohort study.

Epilepsia 2020 03 4;61(3):445-454. Epub 2020 Feb 4.

Department of Neurosciences, Central Clinical School, Alfred Hospital, Monash University, Melbourne, Victoria, Australia.

Objective: To examine the factors and reasons influencing treatment initiation decisions in patients with newly diagnosed epilepsy.

Methods: We assessed antiseizure medication initiation decisions in adults with newly diagnosed epilepsy seen at first seizure clinics in Western Australia between 1999 and 2016 and followed to 2018.

Results: Of 610 patients (median age 40 years, 61.0% male), 426 (69.8%) were diagnosed after two or more seizures and 184 (30.2%) after a single seizure with risk factors for recurrence. Treatment was commenced in 427 patients (70.0%) at diagnosis, 112 (18.4%) during follow-up, mostly after further seizures, whereas 71 (11.6%) remained untreated at last follow-up. Elders (≥65 years, odds ratio [OR] = 3.06, 95% confidence interval [CI]: 1.62-5.80), more seizures (OR = 3.48, 95% CI: 2.03-5.96), and epileptogenic lesions on neuroimaging (OR = 2.15, 95% CI: 1.26-3.68) had a higher likelihood of treatment at diagnosis. Patients with less than one seizure per year within the preceding year (OR = 0.40, 95% CI: 0.21-0.73) and of higher socioeconomic status (OR = 0.985, 95% CI: 0.977-0.994) were less likely to be treated. For 93 patients (15.2%), treatment was not recommended at diagnosis, most commonly because only a single seizure had occurred. Ninety patients (14.8%) declined recommended treatment, mostly because they were unconvinced of the need for treatment or the diagnosis.

Significance: Thirty percent of adults with newly diagnosed epilepsy were not immediately treated. Treatment initiation in this real-world cohort was influenced by age, number of seizures prior to diagnosis, imaging findings, patient preferences, and socioeconomic status.
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http://dx.doi.org/10.1111/epi.16439DOI Listing
March 2020

The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities.

Int J Mol Sci 2019 Jul 29;20(15). Epub 2019 Jul 29.

Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.

Insulin is a promising drug for the treatment of diseases associated with brain damage. However, the mechanism of its neuroprotective action is far from being understood. Our aim was to study the insulin-induced protection of cortical neurons in oxidative stress and its mechanism. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. The insulin neuroprotection was shown to depend on insulin concentration in the nanomolar range. Insulin decreased the reactive oxygen species formation in neurons. The insulin-induced modulation of various protein kinase activities was studied at eight time-points after neuronal exposure to prooxidant (hydrogen peroxide). In prooxidant-exposed neurons, insulin increased the phosphorylation of GSK-3beta at Ser (thus inactivating it), which resulted from Akt activation. Insulin activated ERK1/2 in neurons 5-30 min after cell exposure to prooxidant. Hydrogen peroxide markedly activated AMPK, while it was for the first time shown that insulin inhibited it in neurons at periods of the most pronounced activation by prooxidant. Insulin normalized Bax/Bcl-2 ratio and mitochondrial membrane potential in neurons in oxidative stress. The inhibitors of the PI3K/Akt and MEK1/2/ERK1/2 signaling pathways and the AMPK activator reduced the neuroprotective effect of insulin. Thus, the protective action of insulin on cortical neurons in oxidative stress appear to be realized to a large extent through activation of Akt and ERK1/2, GSK-3beta inactivation, and inhibition of AMPK activity increased by neuronal exposure to prooxidant.
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http://dx.doi.org/10.3390/ijms20153702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696072PMC
July 2019

α-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress.

Int J Mol Sci 2017 Jan 21;18(1). Epub 2017 Jan 21.

Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.

The aim of the present work is to study the mechanism of the α-tocopherol (α-T) protective action at nanomolar and micromolar concentrations against H₂O₂-induced brain cortical neuron death. The mechanism of α-T action on neurons at its nanomolar concentrations characteristic for brain extracellular space has not been practically studied yet. Preincubation with nanomolar and micromolar α-T for 18 h was found to increase the viability of cortical neurons exposed to H₂O₂; α-T effect was concentration-dependent in the nanomolar range. However, preincubation with nanomolar α-T for 30 min was not effective. Nanomolar and micromolar α-T decreased the reactive oxygen species accumulation induced in cortical neurons by the prooxidant. Using immunoblotting it was shown that preincubation with α-T at nanomolar and micromolar concentrations for 18 h prevented Akt inactivation and decreased PKCδ activation induced in cortical neurons by H₂O₂. α-T prevented the ERK1/2 sustained activation during 24 h caused by H₂O₂. α-T at nanomolar and micromolar concentrations prevented a great increase of the proapoptotic to antiapoptotic proteins (Bax/Bcl-2) ratio, elicited by neuron exposure to H₂O₂. The similar neuron protection mechanism by nanomolar and micromolar α-T suggests that a "more is better" approach to patients' supplementation with vitamin E or α-T is not reasonable.
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http://dx.doi.org/10.3390/ijms18010216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297845PMC
January 2017

GM1 ganglioside activates ERK1/2 and Akt downstream of Trk tyrosine kinase and protects PC12 cells against hydrogen peroxide toxicity.

Neurochem Res 2014 Nov 13;39(11):2262-75. Epub 2014 Sep 13.

Department of Comparative Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez Avenue, 44, Saint Petersburg, 194223, Russian Federation.

Ganglioside GM1 at micro- and nanomolar concentrations was shown to increase the viability of pheochromocytoma PC12 cells exposed to hydrogen peroxide and diminish the accumulation of reactive oxygen species and oxidative inactivation of Na(+),K(+)-ATPase, the effects of micromolar GM1 being more pronounced than those of nanomolar GM1. These effects of GM1 were abolished by Trk receptor tyrosine kinase inhibitor and diminished by MEK1/2, phosphoinositide 3-kinase and protein kinase C inhibitors. Hydrogen peroxide activates Trk tyrosine kinase; Akt and ERK1/2 are activated downstream of this protein kinase. GM1 was found to activate Trk receptor tyrosine kinase in PC12 cells. GM1 (100 nM and 10 µM) increased the basal activity of Akt, but did not change Akt activity in cells exposed to hydrogen peroxide. Basal ERK1/2 activity in PC12 cells was increased by GM1 at a concentration of 10 µM, but not at nanomolar concentrations. Activation of ERK1/2 by hydrogen peroxide was enhanced by GM1 at a concentration of 10 µM and to a lesser extent at a concentration of 100 nM. Thus, the protective and metabolic effects of GM1 ganglioside on PC12 cells exposed to hydrogen peroxide appear to depend on the activation of Trk receptor tyrosine kinase and downstream activation of Akt and ERK1/2.
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http://dx.doi.org/10.1007/s11064-014-1428-6DOI Listing
November 2014

α-Tocopherol at nanomolar concentration protects PC12 cells from hydrogen peroxide-induced death and modulates protein kinase activities.

Int J Mol Sci 2012 14;13(9):11543-68. Epub 2012 Sep 14.

Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia; E-Mails: (I.O.Z.); (T.V.S.); (L.V.B.); (Y.A.V.); (M.P.R.).

The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H(2)O(2)-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H(2)O(2)-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3-18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H(2)O(2) to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H(2)O(2). Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H(2)O(2)-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H(2)O(2)-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H(2)O(2) in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective.
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http://dx.doi.org/10.3390/ijms130911543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472762PMC
October 2015

Protective and antioxidative effects of GM1 ganglioside in PC12 cells exposed to hydrogen peroxide are mediated by Trk tyrosine kinase.

Neurochem Res 2010 Jan 21;35(1):85-98. Epub 2009 Jul 21.

Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 St. Petersburg, Russian Federation.

GM1 ganglioside was found to increase the survival of PC12 cells exposed to H(2)O(2), its action was blocked by Trk tyrosine kinase inhibitor K-252a. Thus, the inhibition of H(2)O(2) cytotoxic action by GM1 constituted 52.8 +/- 4.3%, but in the presence of 1.0 microM K-252a it was only 11.7 +/- 10.8%, i.e. the effect of GM1 became insignificant. Exposure to GM1 markedly reduced the increased accumulation of reactive oxygen species (ROS) and diminished the inactivation of Na(+),K(+)-ATPase induced in PC12 cells by H(2)O(2), but in the presence of K-252a GM1 did not change these metabolic parameters. The inhibitors of extracellular signal-regulated protein kinase, phosphatidyl inositol 3-kinase and protein kinase C decreased the effects of GM1. A combination of these protein kinase inhibitors reduced inhibition of H(2)O(2) cytotoxic action by GM1 to the larger extent than each of the inhibitors and practically abolished the ability of GM1 to decrease H(2)O(2)-induced ROS accumulation. The protective and antioxidative effects of GM1 in PC12 cells exposed to H(2)O(2) appear to be mediated by activation of Trk receptor tyrosine kinase and the protein kinases downstream from this enzyme.
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http://dx.doi.org/10.1007/s11064-009-0033-6DOI Listing
January 2010

Neuroprotective effect of ganglioside GM1 on the cytotoxic action of hydrogen peroxide and amyloid beta-peptide in PC12 cells.

Neurochem Res 2007 Aug 31;32(8):1302-13. Epub 2007 Mar 31.

Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, St. Petersburg, Russia.

Ganglioside GM1 was shown to increase the viability of PC12 cells exposed to hydrogen peroxide or amyloid beta-peptide (Abeta(25-35)). The PC12 cells transfected with mutant gene (expressing APP(SW)) were found to be more sensitive to oxidative stress than the cells transfected with wild type gene (expressing APP(WT)) or vector-transfected cells, GM1 being effective in enhancing the viability of the cells transfected with mutant gene. The exposure to hydrogen peroxide or Abeta(25-35) results in a partial inactivation of Na(+),K(+)-ATPase in PC12 cells, H(2)O(2) increases MDA accumulation in these cells. But these effects could be partially prevented or practically abolished by GM1 ganglioside. In the presence of the inhibitor of tyrosine kinase of Trk receptors (K-252a) the protective and metabolic effects of GM1 on PC12 cells in conditions of oxidative stress caused by hydrogen peroxide are not observed or are markedly diminished.
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http://dx.doi.org/10.1007/s11064-007-9304-2DOI Listing
August 2007