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Stress Related Pathologies

M V Uthaug, K van Oorsouw, K P C Kuypers, M van Boxtel, N J Broers, N L Mason, S W Toennes, J Riba, J G Ramaekers
RATIONALE: Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects. OBJECTIVES: The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style...
August 13, 2018: Psychopharmacology
Irving E Vega, Andrew Umstead, Cassandra M Wygant, John S Beck, Scott E Counts
BACKGROUND: The lack of diagnostic tools and disease-modifying treatments against Alzheimer's disease (AD) and related disorders, collectively known as tauopathies, have led to a socioeconomic burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome changes that could help us understand the pathogenesis of tau-related pathological hallmarks and/or cellular stress responses associated with tauopathy. These studies, however, need to be conducted taking in consideration brain region specificity and stage of neurodegeneration in order to provide insights about the pathological role of the identified proteins...
August 13, 2018: Current Alzheimer Research
Amit Kumar, Nirmal Singh
AIM: The present study was designed to investigate the outcome of combination of Calcineurin (CaN) inhibitor (Tacrolimus) and Protein Kinase A (PKA) activator (Forskolin), in mouse models of experimental dementia. METHODS: Streptozotocin [STZ, 3mg/kg, injected intracerebroventricular (i.c.v.)] was used to induce memory deficits in NIH mice, while aged mice separately taken served as a natural model of dementia. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals...
August 13, 2018: Current Neurovascular Research
Sánchez Sofía Campos, Natalia P Alza, Gabriela A Salvador
Pathological α-synuclein (α-syn) overexpression and iron (Fe)-induced oxidative stress (OS) are involved in the death of dopaminergic neurons in Parkinson's disease (PD). We have previously characterized the role of triacylglycerol (TAG) formation in the neuronal response to Fe-induced OS. In this work we characterize the role of the α-syn variant A53T during Fe-induced injury and investigate whether lipid metabolism has implications for neuronal fate. To this end, we used the N27 dopaminergic neuronal cell line either untransfected (UT) or stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-A53T-α-syn (A53T α-syn)...
August 9, 2018: Archives of Biochemistry and Biophysics
Rachel Waller, Mark Murphy, Claire J Garwood, Luke Jennings, Paul R Heath, Annabelle Chambers, Fiona E Matthews, Carol Brayne, Paul G Ince, Stephen B Wharton, Julie E Simpson
Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer's disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and -II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging population-representative neuropathology cohort, and examined H2 O2 -modulation of MT transcription by human astrocytes...
August 10, 2018: Glia
Yujie Su, Huifeng Li, Chang Xu, Xiaodan Wang, Jia Xie, Jian G Qin, Liqiao Chen, Erchao Li
DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main active ingredient in an emerging water environment antifoulant, the toxicity and environmental impacts of which need to be further investigated. Thus, this study examined the toxicity of DCOIT on Nile tilapia (Oreochromis niloticus), including its effects on behavior, respiration and energy metabolism as well as the role of endoplasmic reticulum stress (ER stress) in mediating its toxicity and metabolic changes. The changes in fish behavior, respiration, neuronal signal transmission, energy metabolism, ER stress, and liver histology were examined via acute (4 days) and chronic (28 days) exposures to 0, 3, 15, 30 μg/L DCOIT in vivo...
July 11, 2018: Environmental Pollution
Yi-Heng Lee, Hao-Chieh Hsu, Pei-Chen Kao, Young-Ji Shiao, Skye Hsin-Hsien Yeh, Feng-Shiun Shie, Shu-Meng Hsu, Chih-Wen Yeh, Hui-Kang Liu, Shi-Bing Yang, Huey-Jen Tsay
Alzheimer's disease (AD), a progressive neurodegenerative disease is highly associated with metabolic syndromes. We previously demonstrated that glycemic dysregulation and obesity are augmented in high fat diet (HFD)-treated APPswe/PS1dE9 (APP/PS1) transgenic mice. In the current study, the underlying mechanism mediating exacerbated metabolic stresses in HFD APP/PS1 transgenic mice was further examined. APP/PS1 mice developed insulin resistance and, consequently, impaired glucose homeostasis after 10 weeks on HFD...
August 8, 2018: International Journal of Molecular Sciences
David A Prim, Mohamed A Mohamed, Brooks A Lane, Kelley Poblete, Mark A Wierzbicki, Susan M Lessner, Tarek Shazly, John F Eberth
The prevalence of diverse animal models as surrogates for human vascular pathologies necessitate a comprehensive understanding of the differences that exist between species. Comparative passive mechanics are presented here for the common carotid arteries taken from bovine, porcine, ovine, leporine, murine-rat, and murine-mouse specimens. Data is generated using a scalable biaxial mechanical testing device following consistent circumferential (pressure-diameter) and axial (force-length) testing protocols. The structural mechanical response of carotids under equivalent loading, quantified by the deformed inner radius, deformed wall thickness, lumen area compliance and axial force, varies significantly among species but generally follows allometric scaling...
2018: PloS One
Dagmara McGuinness, Suhaib Mohammed, Laura Monaghan, Paul A Wilson, David B Kingsmore, Oliver Shapter, Karen S Stevenson, Shana M Coley, Luke Devey, Robert B Kirkpatrick, Paul G Shiels
Chronic kidney disease and associated comorbidities (diabetes, cardiovascular diseases) manifest with an accelerated ageing phenotype, leading ultimately to organ failure and renal replacement therapy. This process can be modulated by epigenetic and environmental factors which promote loss of physiological function and resilience to stress earlier, linking biological age with adverse outcomes post-transplantation including delayed graft function (DGF). The molecular features underpinning this have yet to be fully elucidated...
August 9, 2018: Aging Cell
Kishore R Kumar, Gautam Wali, Ryan L Davis, Amali C Mallawaarachchi, Elizabeth E Palmer, Velimir Gayevskiy, Andre E Minoche, David Veivers, Marcel E Dinger, Alan Mackay-Sim, Mark J Cowley, Carolyn M Sue
Zellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different PEX genes. This includes PEX16 , an important regulator of peroxisome biogenesis. Using whole genome sequencing, we detected previously unreported, biallelic variants in PEX16 [NM_004813.2:c.658G>A, p.(Ala220Thr) and NM_004813.2:c.830G>A, p.(Arg277Gln)] in an individual with leukodystrophy, spastic paraplegia, cerebellar ataxia, and craniocervical dystonia with normal plasma very long chain fatty acids. Using olfactory-neurosphere derived cells, a population of neural stem cells, we showed patient cells had reduced peroxisome density and increased peroxisome size, replicating previously reported findings in PEX16 cell lines...
September 2018: Molecular Genetics and Metabolism Reports
Mari-Luz Moreno, Salvador Mérida, Francisco Bosch-Morell, María Miranda, Vincent M Villar
Retinitis pigmentosa (RP) is one of the most common clinical subtypes of retinal degeneration (RD), and it is a neurodegenerative disease that could cause complete blindness in humans because it ultimately affects the photoreceptors viability. RP afflicts an estimated 1.5 million patients worldwide. The retina is highly susceptible to oxidative stress which can impair mitochondrial function. Many retina pathologies, such as diabetic retinopathy and secondary cone photoreceptor death in RP, have been related directly or indirectly with mitochondrial dysfunction...
2018: Frontiers in Physiology
Isabel Paiva, Gaurav Jain, Diana F Lázaro, Kristina Gotovac Jerčić, Thomas Hentrich, Cemil Kerimoglu, Raquel Pinho, Èva M Szegő, Susanne Burkhardt, Vincenzo Capece, Rashi Halder, Rezaul Islam, Mary Xylaki, Lucas A Caldi Gomes, Anna-Elisa Roser, Paul Lingor, Julia M Schulze-Hentrich, Fran Borovečki, André Fischer, Tiago F Outeiro
Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms of PD, remains unclear. Here, we used transgenic mice overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional profiles of the two animal models. We found that A30P aSyn promotes strong transcriptional deregulation and increases DNA binding...
August 6, 2018: Neurobiology of Disease
Fabiana Morroni, Giulia Sita, Agnese Graziosi, Eleonora Turrini, Carmela Fimognari, Andrea Tarozzi, Patrizia Hrelia
Alzheimer's disease (AD) is a progressive pathology, where dementia symptoms gradually worsen over a number of years. The hallmarks of AD, such as amyloid β-peptide (Aβ) in senile plaque and neurofibrillary tangles, are strongly intertwined with oxidative stress, which is considered one of the common effectors of the cascade of degenerative events. The endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) is the "master regulator" of the antioxidant response and it is known as an indicator and regulator of oxidative stress...
August 2018: Aging and Disease
Elena Sidorova-Darmos, Rosa Sommer, James H Eubanks
Sirtuin enzymes are a family of highly seven conserved protein deacetylases, namely SIRT1 through SIRT7, whose enzymatic activities require the cofactor nicotinamide adenine dinucleotide (NAD+ ). Sirtuins reside in different compartments within cells, and their activities have been shown to regulate a number of cellular pathways involved in but not limited to stress management, apoptosis and inflammatory responses. Given the importance of mitochondrial functional state in neurodegenerative conditions, the mitochondrial SIRT3 sirtuin, which is the primary deacetylase within mitochondria, has garnered considerable recent attention...
2018: Frontiers in Cellular Neuroscience
Ruzanna Shkhyan, Siyoung Lee, Francesca Gullo, Lei Li, Maria Peleli, Mattias Carlstrom, Andrei S Chagin, Nicholas W Banks, Sean Limfat, Nancy Q Liu, Denis Evseenko
Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i...
August 7, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Kai Kaarniranta, Jakub Kajdanek, Jan Morawiec, Elzbieta Pawlowska, Janusz Blasiak
PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator of many genes involved in energy management and mitochondrial biogenesis. PGC-1α expression is associated with cellular senescence, organismal aging, and many age-related diseases, including AMD (age-related macular degeneration), an important global issue concerning vision loss. We and others have developed a model of AMD pathogenesis, in which stress-induced senescence of retinal pigment epithelium (RPE) cells leads to AMD-related pathological changes...
August 7, 2018: International Journal of Molecular Sciences
Martha M Liu, Christine J Boinett, Anson C K Chan, Julian Parkhill, Michael E P Murphy, Erin C Gaynor
Campylobacter jejuni is a pathogenic bacterium that causes gastroenteritis in humans yet is a widespread commensal in wild and domestic animals, particularly poultry. Using RNA sequencing, we assessed C. jejuni transcriptional responses to medium supplemented with human fecal versus chicken cecal extracts and in extract-supplemented medium versus medium alone. C. jejuni exposed to extracts had altered expression of 40 genes related to iron uptake, metabolism, chemotaxis, energy production, and osmotic stress response...
August 7, 2018: MBio
Mirjana Nacka-Aleksić, Marija Stojanović, Ivan Pilipović, Zorica Stojić-Vukanić, Duško Kosec, Gordana Leposavić
An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression...
2018: PloS One
Ana C Silveira, Jane Pires Dias, Vanessa M Santos, Pedro Fontes Oliveira, Marco G Alves, Luis Rato, Branca M Silva
Diabetes Mellitus (DM) and Alzheimer's disease (AD) are two prevalent diseases in modern societies, which are caused mainly by current lifestyle, aging and genetic alterations. It has already been demonstrated that these two diseases are associated since individuals suffering from DM are prone to develop AD. Conversely, it is also known that individuals with AD are more susceptible to DM, namely type 2 diabetes (T2DM). Therefore, these two pathologies, although completely different in terms of symptomatology, end up sharing several mechanisms at the molecular level, being the most obvious the increase of oxidative stress and inflammation...
August 3, 2018: Current Neuropharmacology
Jae-Hoon Jeong, Jung-Hoon Koo, Joon-Yong Cho, Eun-Bum Kang
Obesity induces oxidative stress by causing hyperglycemia and insulin resistance, while contributing to cognitive and memory decline by inducing insulin resistance in the brain and hyperphosphorylation of Tau proteins. We aimed to investigate the effects of treadmill exercise in improving these obesity-induced pathological phenomena. Sprague-Dawley rats aged 20 weeks were fed a high-fat diet (HFD) for 20 weeks to induce obesity. The rats were subsequently subjected to treadmill exercise (progressively increasing load intensity) for 8 weeks...
August 3, 2018: Brain Research Bulletin
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