The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Gary W. Arendash - One of the best experts on this subject based on the ideXlab platform.
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Electromagnetic treatment to old Alzheimer's mice reverses β-amyloid deposition, modifies cerebral blood flow, and provides selected Cognitive Benefit.
PLOS ONE, 2012Co-Authors: Gary W. Arendash, Maggie Dorsey, Rich Gonzalez, Naoki Tajiri, Takashi Mori, Cesario V. BorlonganAbstract:Few studies have investigated physiologic and Cognitive effects of “long-term" electromagnetic field (EMF) exposure in humans or animals. Our recent studies have provided initial insight into the long-term impact of adulthood EMF exposure (GSM, pulsed/modulated, 918 MHz, 0.25–1.05 W/kg) by showing 6+ months of daily EMF treatment protects against or reverses Cognitive impairment in Alzheimer's transgenic (Tg) mice, while even having Cognitive Benefit to normal mice. Mechanistically, EMF-induced Cognitive Benefits involve suppression of brain β-amyloid (Aβ) aggregation/deposition in Tg mice and brain mitochondrial enhancement in both Tg and normal mice. The present study extends this work by showing that daily EMF treatment given to very old (21–27 month) Tg mice over a 2-month period reverses their very advanced brain Aβ aggregation/deposition. These very old Tg mice and their normal littermates together showed an increase in general memory function in the Y-maze task, although not in more complex tasks. Measurement of both body and brain temperature at intervals during the 2-month EMF treatment, as well as in a separate group of Tg mice during a 12-day treatment period, revealed no appreciable increases in brain temperature (and no/slight increases in body temperature) during EMF “ON" periods. Thus, the neuropathologic/Cognitive Benefits of EMF treatment occur without brain hyperthermia. Finally, regional cerebral blood flow in cerebral cortex was determined to be reduced in both Tg and normal mice after 2 months of EMF treatment, most probably through cerebrovascular constriction induced by freed/disaggregated Aβ (Tg mice) and slight body hyperthermia during “ON" periods. These results demonstrate that long-term EMF treatment can provide general Cognitive Benefit to very old Alzheimer's Tg mice and normal mice, as well as reversal of advanced Aβ neuropathology in Tg mice without brain heating. Results further underscore the potential for EMF treatment against AD.
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long term electromagnetic field treatment increases brain neuronal activity linkage to Cognitive Benefit and therapeutic implications for alzheimer s disease
Journal of Alzheimers Disease & Parkinsonism, 2011Co-Authors: Takashi Mori, Gary W. ArendashAbstract:Although a single exposure to high frequency electromagnetic fields (EMF) appears to increase neuronal activity based on PET/EEG monitoring, the "long-term" effects of daily EMF treatment on neuronal activity have not been evaluated in either humans or animals. In the present study, we report daily EMF treatment over a two-month period to enhance neuronal activity in entorhinal cortex of aged (23 - 28 month old) Alzheimer\'s transgenic mice and littermate normal mice, as indexed by the expression of c-Fos in neurons. Moreover, this enhanced neuronal activity was temporally linked to Cognitive Benefit in the same animals. In view of the impaired neuronal activity that occurs very early and progressively in Alzheimer\'s Disease, we suggest EMF treatment as a viable approach to counter this neuronal hypo-activity and possibly enhance/stabilize Cognitive function.
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long term electromagnetic field treatment enhances brain mitochondrial function of both alzheimer s transgenic mice and normal mice a mechanism for electromagnetic field induced Cognitive Benefit
Neuroscience, 2011Co-Authors: Natasa Dragicevic, Patrick C Bradshaw, Malgorzata Mamcarz, Xiaoyang Lin, Lilly Wang, Chuanhai Cao, Gary W. ArendashAbstract:We have recently reported that long-term exposure to high frequency electromagnetic field (EMF) treatment not only prevents or reverses Cognitive impairment in Alzheimer's transgenic (Tg) mice, but also improves memory in normal mice. To elucidate the possible mechanism(s) for these EMF-induced Cognitive Benefits, brain mitochondrial function was evaluated in aged Tg mice and non-transgenic (NT) littermates following 1 month of daily EMF exposure. In Tg mice, EMF treatment enhanced brain mitochondrial function by 50-150% across six established measures, being greatest in Cognitively-important brain areas (e.g. cerebral cortex and hippocampus). EMF treatment also increased brain mitochondrial function in normal aged mice, although the enhancement was not as robust and less widespread compared to that of Tg mice. The EMF-induced enhancement of brain mitochondrial function in Tg mice was accompanied by 5-10 fold increases in soluble Aβ1-40 within the same mitochondrial preparations. These increases in mitochondrial soluble amyloid-β peptide (Aβ) were apparently due to the ability of EMF treatment to disaggregate Aβ oligomers, which are believed to be the form of Aβ causative to mitochondrial dysfunction in Alzheimer's disease (AD). Finally, the EMF-induced mitochondrial enhancement in both Tg and normal mice occurred through non-thermal effects because brain temperatures were either stable or decreased during/after EMF treatment. These results collectively suggest that brain mitochondrial enhancement may be a primary mechanism through which EMF treatment provides Cognitive Benefit to both Tg and NT mice. Especially in the context that mitochondrial dysfunction is an early and prominent characteristic of Alzheimer's pathogenesis, EMF treatment could have profound value in the disease's prevention and treatment through intervention at the mitochondrial level.
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green tea epigallocatechin 3 gallate egcg reduces β amyloid mediated Cognitive impairment and modulates tau pathology in alzheimer transgenic mice
Brain Research, 2008Co-Authors: Kavon Rezaizadeh, Gary W. Arendash, Frank Fernandez, Maren Jensen, Melissa Runfeldt, Douglas R ShytleAbstract:Abstract We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (−)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased β-amyloid (Aβ) levels and plaques via promotion of the non-amyloidogenic α-secretase proteolytic pathway in “Swedish” mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces Aβ deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both Aβ 1–40 and 1–42 soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial arm water maze (RAWM) testing for working memory indicated that EGCG provided Cognitive Benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced Benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease.
Dieter Edbauer - One of the best experts on this subject based on the ideXlab platform.
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rna dependent intergenerational inheritance of enhanced synaptic plasticity after environmental enrichment
Cell Reports, 2018Co-Authors: Eva Benito, Cemil Kerimoglu, Binu Ramachandran, Tonatiuh Penacenteno, Gaurav Jain, Roman M Stilling, Rezaul Islam, Vincenzo Capece, Qihui Zhou, Dieter EdbauerAbstract:Physical exercise in combination with Cognitive training is known to enhance synaptic plasticity, learning, and memory and lower the risk for various complex diseases including Alzheimer's disease. Here, we show that exposure of adult male mice to an environmental enrichment paradigm leads to enhancement of synaptic plasticity and cognition also in the next generation. We show that this effect is mediated through sperm RNA and especially miRs 212/132. In conclusion, our study reports intergenerational inheritance of an acquired Cognitive Benefit and points to specific miRs as candidates mechanistically involved in this type of transmission.
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rna dependent intergenerational inheritance of enhanced synaptic plasticity after environmental enrichment
bioRxiv, 2017Co-Authors: Eva Benito, Cemil Kerimoglu, Binu Ramachandran, Gaurav Jain, Roman M Stilling, Vincenzo Capece, Qihui Zhou, Tonatiuh Pena, Susanne Burkhardt, Dieter EdbauerAbstract:Physical exercise in combination with Cognitive training is known to enhance synaptic plasticity, learning & memory and lower the risk for various complex diseases including Alzheimer disease. Here we show that exposure of adult male mice to an environmental enrichment paradigm leads to enhancement of synaptic plasticity and cognition also in the next generation. We show that the effect is mediated through sperm RNA and is explained by microRNAs 212/132. In conclusion, our study reports intergenerational inheritance of an acquired Cognitive Benefit and points to specific microRNAs as candidates mechanistically involved in this type of transmission.
F D R Hobbs - One of the best experts on this subject based on the ideXlab platform.
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a randomized controlled trial of the effect of thyroxine replacement on Cognitive function in community living elderly subjects with subclinical hypothyroidism the birmingham elderly thyroid study
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Jim Parle, Lesley Roberts, Scott G Wilson, Helen M Pattison, Andrea K Roalfe, M S Haque, C Heath, M C Sheppard, J A Franklyn, F D R HobbsAbstract:Context: Subclinical hypothyroidism (SCH) and Cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T4 replacement therapy in SCH confers Cognitive Benefit. Objective: Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves Cognitive function. Design and Setting: We conducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. Patients: Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. Intervention: T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 μg T4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T4 (31 female...
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a randomized controlled trial of the effect of thyroxine replacement on Cognitive function in community living elderly subjects with subclinical hypothyroidism the birmingham elderly thyroid study
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Jim Parle, Lesley Roberts, Helen M Pattison, Andrea K Roalfe, M S Haque, C Heath, M C Sheppard, J A Franklyn, Sue Wilson, F D R HobbsAbstract:Context: Subclinical hypothyroidism (SCH) and Cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T 4 replacement therapy in SCH confers Cognitive Benefit. Objective: Our objective was to determine whether administration of T 4 replacement to achieve biochemical euthyroidism in subjects with SCH improves Cognitive function. Design and Setting:Weconducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. Patients: Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. Intervention: T 4 or placebo was given at an initial dosage of one tablet of either placebo or 25 μg T 4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T 4 (31 females, 21 males; mean age 73.5 yr, range 65-94 yr); 42 subjects received placebo (26 females, 16 males; mean age 74.2 yr, 66-84 yr). Main Outcome Measures: Mini-Mental State Examination, Middlesex Elderly Assessment of Mental State (covering orientation, learning, memory, numeracy, perception, attention, and language skills), and Trail-Making A and B were administered. Results: Eighty-two percent and 84% in the T 4 group achieved euthyroidism at 6- and 12-month intervals, respectively. Cognitive function scores at baseline and 6 and 12 months were as follows: Mini-Mental State Examination T 4 group, 28.26, 28.9, and 28.28, and placebo group, 28.17, 27.82, and 28.25 [not significant (NS)]; Middlesex Elderly Assessment of Mental State T 4 group, 11.72, 11.67, and 11.78, and placebo group, 11.21, 11.47, and 11.44 (NS); Trail-Making A T 4 group, 45.72, 47.65, and 44.52, and placebo group, 50.29, 49.00, and 46.97 (NS); and Trail-Making B T 4 group, 110.57, 106.61, and 96.67, and placebo group, 131.46, 119.13, and 108.38 (NS). Linear mixed-model analysis demonstrated no significant changes in any of the measures of Cognitive function over time and no between-group difference in Cognitive scores at 6 and 12 months. Conclusions: This RCT provides no evidence for treating elderly subjects with SCH with T 4 replacement therapy to improve Cognitive function. Copyright © 2010 by The Endocrine Society.
Eva Benito - One of the best experts on this subject based on the ideXlab platform.
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rna dependent intergenerational inheritance of enhanced synaptic plasticity after environmental enrichment
Cell Reports, 2018Co-Authors: Eva Benito, Cemil Kerimoglu, Binu Ramachandran, Tonatiuh Penacenteno, Gaurav Jain, Roman M Stilling, Rezaul Islam, Vincenzo Capece, Qihui Zhou, Dieter EdbauerAbstract:Physical exercise in combination with Cognitive training is known to enhance synaptic plasticity, learning, and memory and lower the risk for various complex diseases including Alzheimer's disease. Here, we show that exposure of adult male mice to an environmental enrichment paradigm leads to enhancement of synaptic plasticity and cognition also in the next generation. We show that this effect is mediated through sperm RNA and especially miRs 212/132. In conclusion, our study reports intergenerational inheritance of an acquired Cognitive Benefit and points to specific miRs as candidates mechanistically involved in this type of transmission.
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rna dependent intergenerational inheritance of enhanced synaptic plasticity after environmental enrichment
bioRxiv, 2017Co-Authors: Eva Benito, Cemil Kerimoglu, Binu Ramachandran, Gaurav Jain, Roman M Stilling, Vincenzo Capece, Qihui Zhou, Tonatiuh Pena, Susanne Burkhardt, Dieter EdbauerAbstract:Physical exercise in combination with Cognitive training is known to enhance synaptic plasticity, learning & memory and lower the risk for various complex diseases including Alzheimer disease. Here we show that exposure of adult male mice to an environmental enrichment paradigm leads to enhancement of synaptic plasticity and cognition also in the next generation. We show that the effect is mediated through sperm RNA and is explained by microRNAs 212/132. In conclusion, our study reports intergenerational inheritance of an acquired Cognitive Benefit and points to specific microRNAs as candidates mechanistically involved in this type of transmission.
Alberto Pilotto - One of the best experts on this subject based on the ideXlab platform.
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Immunotherapy for Alzheimer's disease: from anti-β-amyloid to tau-based immunization strategies.
Immunotherapy, 2012Co-Authors: Francesco Panza, Vincenza Frisardi, Bruno P. Imbimbo, Giancarlo Logroscino, Davide Seripa, Andrea Santamato, V. Solfrizzi, Antonio Greco, Alberto PilottoAbstract:The exact mechanisms leading to Alzheimer’s disease (AD) are largely unknown, limiting the identification of effective disease-modifying therapies. The two principal neuropathological hallmarks of AD are extracellular b-amyloid (Ab), peptide deposition (senile plaques) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. During the last decade, most of the efforts of the pharmaceutical industry were directed against the production and accumulation of Ab. The most innovative of the pharmacological approaches was the stimulation of Ab clearance from the brain of AD patients via the administration of Ab antigens (active vaccination) or anti-Ab antibodies (passive vaccination). Several active and passive anti-Ab vaccines are under clinical investigation. Unfortunately, the first active vaccine (AN1792, consisting of preaggregate Ab and an immune adjuvant, QS - 21) was abandoned because it caused meningoencephalitis in approximately 6% of treated patients. Anti-Ab monoclonal antibodies (bapineuzumab and solanezumab) are now being developed. The clinical results of the initial studies with bapineuzumab were equivocal in terms of Cognitive Benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E e4 carriers), has raised concerns on the safety of these antibodies directed against the N - terminus of the Ab peptide. Solanezumab, a humanized anti-Ab monoclonal antibody directed against the midregion of the Ab peptide, was shown to neutralize soluble Ab species. Phase II studies showed a good safety profile of solanezumab, while studies on cerebrospinal and plasma biomarkers documented good signals of pharmacodynamic activity. Although some studies suggested that active immunization may be effective against tau in animal models of AD, very few studies regarding passive immunization against tau protein are currently available. The results of the large, ongoing Phase III trials with bapineuzumab and solanezumab will tell us if monoclonal anti-Ab antibodies may slow down the rate of deterioration of AD. Based on the new diagnostic criteria of AD and on recent major failures of anti-Ab drugs in mild-to-moderate AD patients, one could argue that clinical trials on potential disease-modifying drugs, including immunological approaches, should be performed in the early stages of AD.