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https://www.readbyqxmd.com/read/27143420/presenilin-1-promotes-trypsin-induced-neuroprotection-via-the-par2-erk-signaling-pathway-effects-of-presenilin-1-fad-mutations
#1
Angeliki M Nikolakopoulou, Anastasios Georgakopoulos, Nikolaos K Robakis
Mutants of presenilin 1 (PS1) increase neuronal cell death causing autosomal-dominant familial Alzheimer's disease (FAD). Recent literature shows that treatment of neuronal cultures with low concentrations of trypsin, a member of the serine family of proteases, protects neurons from toxic insults by binding to the proteinase-activated receptor 2 and stimulating survival kinase extracellular signal-regulated kinase (ERK 1/2). Other studies show that PS1 is necessary for the neuroprotective activity of specific neurotrophic factors, such as brain-derived neurotrophic factor, against excitotoxicity and oxidative stress...
June 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27028704/a-model-of-excitotoxic-brain-injury-in-larval-zebrafish-potential-application-for-high-throughput-drug-evaluation-to-treat-traumatic-brain-injury
#2
Victoria McCutcheon, Eugene Park, Elaine Liu, Youdong Wang, Xiao-Yan Wen, Andrew J Baker
Traumatic brain injury (TBI) is a leading cause of death and morbidity with no effective therapeutic treatments for secondary injury. Preclinical drug evaluation in rodent models of TBI is a lengthy process. In this regard, the zebrafish has numerous advantages to address the technical and time-dependent obstacles associated with drug evaluation. We developed a reproducible brain injury using glutamate excitoxicity in zebrafish larvae, a known initiator of delayed cell death in TBI. Glutamate challenge resulted in dose-dependent lethality over an 84-h observation period...
June 2016: Zebrafish
https://www.readbyqxmd.com/read/26547950/-homocysteine-induced-membrane-currents-calcium-responses-and-changes-of-mitochondrial-potential-in-rat-cortical-neurons
#3
P A Abushik, T V Karelina, D A Sibarov, J D Stepanenko, R Giniatullin, S M Antonov
Homocysteine, a sulfur-containing amino acid, exhibits neurotoxic effects and is involved in the pathogenesis of several major neurodegenerative disorders. In contrast to well studied excitoxicity of glutamate, the mechanism of homocysteine neurotoxicity is not clearly understood. By using whole-cell patch-clamp, calcium imaging (fluo-3) and measurements of mitochondrial membrane potential (rhodamine 123) we studied transmembrane currents, calcium signals and changes in mitochondrial membrane potential induced by homocysteine versus responses induced by NMDA and glutamate in cultured rat cortical neurons...
July 2015: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
https://www.readbyqxmd.com/read/26332830/neuroprotective-effects-of-multifaceted-hybrid-agents-targeting-mao-cholinesterase-iron-and-%C3%AE-amyloid-in-ageing-and-alzheimer-s-disease
#4
Orly Weinreb, Tamar Amit, Orit Bar-Am, Moussa B H Youdim
UNLABELLED: Alzheimer's disease (AD) is accepted nowadays as a complex neurodegenerative disorder with multifaceted cerebral pathologies, including extracellular deposition of amyloid β peptide-containing plaques, intracellular neurofibrillary tangles, progressive loss of cholinergic neurons, metal dyshomeostasis, mitochondrial dysfunction, neuroinflammation, glutamate excitoxicity, oxidative stress and increased MAO enzyme activity. This may explain why it is currently widely accepted that a more effective therapy for AD would result from the use of multifunctional drugs, which may affect more than one brain target involved in the disease pathology...
July 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/25822337/conantokin-g-attenuates-detrimental-effects-of-nmdar-hyperactivity-in-an-ischemic-rat-model-of-stroke
#5
Rashna Balsara, Alexander Dang, Deborah L Donahue, Tiffany Snow, Francis J Castellino
The neuroprotective activity of conantokin-G (con-G), a naturally occurring antagonist of N-methyl-D-aspartate receptors (NMDAR), was neurologically and histologically compared in the core and peri-infarct regions after ischemia/reperfusion brain injury in male Sprague-Dawley rats. The contralateral regions served as robust internal controls. Intrathecal injection of con-G, post-middle carotid artery occlusion (MCAO), caused a dramatic decrease in brain infarct size and swelling at 4 hr, compared to 26 hr, and significant recovery of neurological deficits was observed at 26 hr...
2015: PloS One
https://www.readbyqxmd.com/read/25678559/amyloid-%C3%AE-deposition-in-mild-cognitive-impairment-is-associated-with-increased-hippocampal-activity-atrophy-and-clinical-progression
#6
Willem Huijbers, Elizabeth C Mormino, Aaron P Schultz, Sarah Wigman, Andrew M Ward, Mykol Larvie, Rebecca E Amariglio, Gad A Marshall, Dorene M Rentz, Keith A Johnson, Reisa A Sperling
Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum...
April 2015: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/25206077/the-mechanism-of-degeneration-of-striatal-neuronal-subtypes-in-huntington-disease
#7
REVIEW
Azadeh A Rikani, Zia Choudhry, Adnan M Choudhry, Nasir Rizvi, Huma Ikram, Nusrat J Mobassarah, Sagun Tulli
The pattern of neurodegeneration in Huntington's disease (HD) is very characteristic of regional locations as well as that of neuronal types in striatum. The different striatal neuronal populations demonstrate different degree of degeneration in response to various pathological events in HD. In the striatum, medium spiny GABA neurons (MSN) are preferentially degenerate while others are relatively spared. Vulnerability of specific neuronal populations within the striatum to pathological events constitutes an important hallmark of degeneration in HD...
July 2014: Annals of Neurosciences
https://www.readbyqxmd.com/read/24961520/cannabinoids-well-suited-candidates-for-the-treatment-of-perinatal-brain-injury
#8
David Fernández-López, Ignacio Lizasoain, Maria Angeles Moro, José Martínez-Orgado
Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth, including neonatal asphyxia, neonatal hypoxia-ischemia and stroke-induced focal ischemia. Typical manifestations of these conditions are the presence of glutamate excitoxicity, neuroinflammation and oxidative stress, the combination of which can potentially result in apoptotic-necrotic cell death, generation of brain lesions and long-lasting functional impairment. In spite of the high incidence of perinatal brain injury, the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited...
2013: Brain Sciences
https://www.readbyqxmd.com/read/24934359/biomarkers-and-future-targets-for-development-in-amyotrophic-lateral-sclerosis
#9
REVIEW
Parvathi Menon, Matthew C Kiernan, Steve Vucic
Although the pathophysiological mechanisms underlying the development of amyotrophic lateral sclerosis (ALS) remain to be fully elucidated, there have been significant advances in the understanding of ALS pathogenesis, with evidence emerging of a complex interaction between genetic factors and dysfunction of vital molecular pathways. Glutamate- mediated excitoxicity is an important pathophysiological pathway in ALS, and was identified as an important therapeutic biomarker leading to development of the only pharmacologically based disease-modifying treatment currently available for ALS...
2014: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/24871660/s-allyl-l-cysteine-protects-the-retina-against-kainate-excitotoxicity-in-the-rat
#10
Hsiao-Ming Chao, Ing-Ling Chen, Jorn-Hon Liu
Excitotoxicity has been proposed to play a pivotal role in retinal ischemia. Retinal ischemia-associated ocular disorders are vision threatening. The aim was to also examine whether and how S-allyl L-cysteine (SAC) can protect the retina against kainate excitotoxicity. In vivo retinal excitotoxicity was induced by an intravitreous injection of 100 μM kainate into a Wistar rat eye for 1 day. The management and mechanisms involved in the processes were evaluated by electrophysiology, immunohistochemistry, histopathology, and various biochemical approaches...
2014: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/24699060/effects-of-lithium-and-valproic-acid-on-bdnf-protein-and-gene-expression-in-an-in-vitro-human-neuron-like-model-of-degeneration
#11
Nicoletta Croce, Aleksander A Mathé, Francesca Gelfo, Carlo Caltagirone, Sergio Bernardini, Francesco Angelucci
One of the common effects of lithium (Li) and valproic acid (VPA) is their ability to protect against excitotoxic insults. Neurodegenerative and neuropsychiatric diseases may be also associated with altered trophic support of brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin in the central nervous system. However, despite these evidences, the effect of Li-VPA combination on BDNF after excitoxic insult has been inadequately investigated. We address this issue by exposing a human neuroblastoma cell line (SH-SY5Y) to neurotoxic concentration of L-glutamate and exploring whether the neuroprotective action of Li-VPA on these cells is associated with changes in BDNF protein and mRNA levels...
October 2014: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/24646274/the-temporal-and-spatial-dynamics-of-glyoxalase-i-following-excitoxicity-and-brain-ischaemia
#12
REVIEW
Philipp Pieroh, Gerd Birkenmeier, Faramarz Dehghani
MG (methylglyoxal) is an inevitable metabolite derived from glycolysis leading to protein modification, mitochondrial dysfunction and cell death. The ubiquitous glyoxalase system detoxifies MG under GSH consumption by mean of Glo1 (glyoxalase I) as the rate-limiting enzyme. Neurons are highly vulnerable to MG, whereas astrocytes seem less susceptible due to their highly expressed glyoxalases. In neurodegenerative diseases, MG and Glo1 were found to be pivotal players in chronic CNS (central nervous system) diseases...
April 2014: Biochemical Society Transactions
https://www.readbyqxmd.com/read/24617747/the-role-of-pedunculopontine-nucleus-in-choice-behavior-under-risk
#13
Mona Leblond, Tatyana Sukharnikova, Chunxiu Yu, Mark A Rossi, Henry H Yin
The dopaminergic projections to the basal ganglia have long been implicated in reward-guided behavior and decision-making, yet little is known about the role of the posterior pedunculopontine nucleus (pPPN), a major source of excitatory input to the mesolimbic dopamine system. Here we studied the contributions of the pPPN to decision-making under risk, using excitoxic lesions and reversible inactivation in rats. Rats could choose between two options - a small but certain reward on one lever; or a large but uncertain reward on the other lever...
May 2014: European Journal of Neuroscience
https://www.readbyqxmd.com/read/24500615/impact-of-repeated-procedural-pain-related-stress-in-infants-born-very-preterm
#14
REVIEW
Jillian Vinall, Ruth E Grunau
The majority of infants born very preterm (24-32 wk gestational age) now survive; however, long-term neurodevelopmental and behavioral problems remain a concern. As part of their neonatal care, very preterm infants undergo repeated painful procedures during a period of rapid brain development and programming of stress systems. Infants born this early have the nociceptive circuitry required to perceive pain, however, their sensory systems are functionally immature. An imbalance of excitatory vs. inhibitory processes leads to increased nociceptive signaling in the central nervous system...
May 2014: Pediatric Research
https://www.readbyqxmd.com/read/24286859/neuroprotective-and-cognitive-enhancing-effects-of-a-multi-targeted-food-intervention-in-an-animal-model-of-neurodegeneration-and-depression
#15
COMPARATIVE STUDY
Yuliya E Borre, Theodora Panagaki, Pim J Koelink, Mary E Morgan, Hendrikus Hendriksen, Johan Garssen, Aletta D Kraneveld, Berend Olivier, Ronald S Oosting
Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated...
April 2014: Neuropharmacology
https://www.readbyqxmd.com/read/23907317/iqgap1-expression-in-spared-ca1-neurons-after-an-excitotoxic-lesion-in-the-mouse-hippocampus
#16
Min-Hee Yi, Sooil Kim, Enji Zhang, Joon Won Kang, Jin Bong Park, Young Ho Lee, Chun Kee Chung, Yong Min Kim, Dong Woon Kim
Repeated seizures induce permanent alterations in the hippocampal circuits in experimental models with intractable temporal lobe epilepsy. Sprouting and synaptic reorganization induced by seizures has been well-studied in the mossy fiber pathway. However, studies investigating sprouting and synaptic reorganization beyond the mossy fiber pathway are limited. The present study examined the biochemical changes of CA1 pyramidal neurons undergoing morphological changes after excitotoxicity-induced hippocampal CA3 neuronal death...
October 2013: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/23766625/cgs-19755-selfotel-a-novel-neuroprotective-agent-against-cns-injury
#17
Miguel A Pérez-Pinzón, Gary K Steinberg
The hypothesis that excitoxicity is a mechanism of damage following different types of cerebral injury including global and focal ischemia (34), and head and spinal cord trauma (6,7,9,25) has been supported by numerous findings. During ischemia for example, glutamate neurotoxicity is mediated in part through N-methyl-D-aspartate (NMDA) receptors, since selective antagonists to this receptor protect against hypoxic-ischemic injury (10,35,41). In the last few years, different NMDA antagonists have been developed and tested; they can be divided into competitive and noncompetitive antagonists...
September 1, 1996: CNS Drug Reviews
https://www.readbyqxmd.com/read/23483239/atrophy-of-pyramidal-neurons-and-increased-stress-induced-glutamate-levels-in-ca3-following-chronic-suppression-of-adult-neurogenesis
#18
Robert J Schloesser, Dennisse V Jimenez, Nicholas F Hardy, Daniel Paredes, Briony J Catlow, Husseini K Manji, Ronald D McKay, Keri Martinowich
Following their birth in the adult hippocampal dentate gyrus, newborn progenitor cells migrate into the granule cell layer where they differentiate, mature, and functionally integrate into existing circuitry. The hypothesis that adult hippocampal neurogenesis is physiologically important has gained traction, but the precise role of newborn neurons in hippocampal function remains unclear. We investigated whether loss of new neurons impacts dendrite morphology and glutamate levels in area CA3 of the hippocampus by utilizing a human GFAP promoter-driven thymidine kinase genetic mouse model to conditionally suppress adult neurogenesis...
May 2014: Brain Structure & Function
https://www.readbyqxmd.com/read/23354057/medial-prefrontal-cortex-lesions-impair-decision-making-on-a-rodent-gambling-task-reversal-by-d1-receptor-antagonist-administration
#19
Tracie A Paine, Samuel K Asinof, Geoffrey W Diehl, Anna Frackman, Joseph Leffler
Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using "gambling" tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT). In this task, rats have to decide between 1 of 4 possible options: 2 options are considered "advantageous" and lead to greater net rewards (food pellets) than the other 2 "disadvantageous" options...
April 15, 2013: Behavioural Brain Research
https://www.readbyqxmd.com/read/23057965/neuroprotection-afforded-by-adenosine-a2a-receptor-blockade-is-modulated-by-corticotrophin-releasing-factor-crf-in-glutamate-injured-cortical-neurons
#20
Jorge S Valadas, Vânia L Batalha, Diana G Ferreira, Rui Gomes, Joana E Coelho, Ana M Sebastião, Maria José Diógenes, Luísa V Lopes
In situations of hypoxia, glutamate excitotoxicity induces neuronal death. The release of extracellular adenosine is also triggered and is accompanied by an increase of the stress mediator, corticotrophin-releasing factor (CRF). Adenosine A(2A) receptors contribute to glutamate excitoxicity and their blockade is effective in stress-induced neuronal deficits, but the involvement of CRF on this effect was never explored. We now evaluated the interaction between A(2A) and CRF receptors (CRFR) function, upon glutamate insult...
December 2012: Journal of Neurochemistry
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