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https://www.readbyqxmd.com/read/29031088/probing-the-correlation-of-neuronal-loss-neurofibrillary-tangles-and-cell-death-markers-across-the-alzheimer-s-disease-braak-stages-a-quantitative-study-in-humans
#1
Panos Theofilas, Alexander J Ehrenberg, Austin Nguy, Julia M Thackrey, Sara Dunlop, Maria B Mejia, Ana T Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Claudia K Suemoto, Camila F Nascimento, Marcus Chin, Daniel Medina-Cleghorn, Ana Maria Cuervo, Michelle Arkin, William W Seeley, Bruce L Miller, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29031076/synthesis-and-evaluation-of-new-pyridyl-pyrazinyl-thiourea-derivatives-neuroprotection-against-amyloid-%C3%AE-induced-toxicity
#2
Jung-Eun Park, Ahmed Elkamhawy, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Sora Paik, Beoung-Geon Park, Eun Joo Roh
Herein, we report synthesis and evaluation of new twenty six small molecules against β amyloid (Aβ)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aβ-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Fifteen derivatives eliciting increased green to red fluorescence percentage less than 40.0% were evaluated for their impact on ATP production, cell viability and neuroprotection against Aβ-induced neuronal cell death...
September 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031072/recent-advances-in-discovery-and-development-of-natural-products-as%C3%A2-source-for-anti-parkinson-s-disease-lead-compounds
#3
REVIEW
Hongjia Zhang, Lan Bai, Jun He, Lei Zhong, Xingmei Duan, Liang Ouyang, Yuxuan Zhu, Ting Wang, Yiwen Zhang, Jianyou Shi
Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Although the cause remains unknown, several pathological processes and central factors such as oxidative stress, mitochondrial injury, inflammatory reactions, abnormal deposition of α-synuclein, and cell apoptosis have been reported. Currently, anti-PD drugs are classified into two major groups: drugs that affect dopaminergic neurons and anti-cholinergic drugs. Unfortunately, the existing conventional strategies against PD are with numerous side effects, and cannot fundamentally improve the degenerative process of dopaminergic neurons...
September 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031050/paraquat-affects-mitochondrial-bioenergetics-dopamine-system-expression-and-locomotor-activity-in-zebrafish-danio-rerio
#4
Xiao H Wang, Christopher L Souders, Yuan H Zhao, Christopher J Martyniuk
The dipyridyl herbicide paraquat induces oxidative stress in cells and is implicated in adult neurodegenerative diseases. However, less is known about paraquat toxicity in early stages of vertebrate development. To address this gap, zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 μM paraquat for 96 h. Paraquat did not induce significant mortality nor deformity in embryos and larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial respiration was related to earlier hatch times, oxygen consumption rate was measured in whole embryos...
October 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/29029315/7-8-dihydroxyflavone-rescues-lead-induced-impairment-of-vesicular-release-a-novel-therapeutic-approach-for-lead-intoxicated-children
#5
Xiao-Lei Zhang, Jennifer L McGlothan, Omid Miry, Kirstie H Stansfield, Meredith K Loth, Patric K Stanton, Tomás R Guilarte
Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits.In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling...
October 4, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29029290/nmda-receptor-mediated-ca2-influx-in-the-absence-of-mg2-block-disrupts-rest-activity-rhythms-in-drosophila
#6
Qian Song, Ge Feng, Jiaxing Zhang, Xuechun Xia, Min Ji, Lei Lv, Yong Ping
Introduction: The correlated activation of pre- and postsynaptic neurons is essential for the NMDA receptor-mediated Ca2+ influx by removing Mg2+ from block site and NMDA receptors have been implicated in phase resetting of circadian clocks. So we assessed rest:activity rhythms in Mg2+ block defective animals. Methods: Using Drosophila locomotor monitoring system, we checked circadian rest:activity rhythms of different mutants under constant darkness (DD) and light:dark (LD) conditions...
October 3, 2017: Sleep
https://www.readbyqxmd.com/read/29029261/selective-enhancement-of-domoic-acid-toxicity-in-primary-cultures-of-cerebellar-granule-cells-by-lowering-extracellular-na-concentration
#7
Anabel Pérez-Gómez, David Cabrera-García, Davide Warm, Ann M Marini, Javier Salas Puig, Maria Teresa Fernández-Sánchez, Antonello Novelli
Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was ̴ 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+...
September 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29028941/dysregulation-of-cortical-neuron-dna-methylation-profile-in-autism-spectrum-disorder
#8
Stefano Nardone, Dev Sharan Sams, Antonino Zito, Eli Reuveni, Evan Elliott
Autism Spectrum Disorder (ASD) is a complex neuropsychiatric syndrome whose etiology includes genetic and environmental components. Since epigenetic marks are sensitive to environmental insult, they may be involved in the development of ASD. Initial brain studies have suggested a dysregulation of epigenetic marks in ASD. However, due to cellular heterogeneity in the brain, these studies have not determined if there is a true change in the neuronal epigenetic signature. Here, we report a genome-wide methylation study on fluorescence-activated cell sorting-sorted neuronal nuclei from the frontal cortex of 16 male ASD and 15 male control subjects...
September 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29028940/optogenetic-activation-of-the-sensorimotor-cortex-reveals-local-inhibitory-and-global-excitatory-inputs-to-the-basal-ganglia
#9
Mitsunori Ozaki, Hiromi Sano, Shigeki Sato, Mitsuhiro Ogura, Hajime Mushiake, Satomi Chiken, Naoyuki Nakao, Atsushi Nambu
To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively...
September 22, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29028808/functional-characterization-of-gabaa-receptor-mediated-modulation-of-cortical-neuron-network-activity-in-microelectrode-array-recordings
#10
Benjamin M Bader, Anne Steder, Anders Bue Klein, Bente Frølund, Olaf H U Schroeder, Anders A Jensen
The numerous γ-aminobutyric acid type A receptor (GABAAR) subtypes are differentially expressed and mediate distinct functions at neuronal level. In this study we have investigated GABAAR-mediated modulation of the spontaneous activity patterns of primary neuronal networks from murine frontal cortex by characterizing the effects induced by a wide selection of pharmacological tools at a plethora of activity parameters in microelectrode array (MEA) recordings. The basic characteristics of the primary cortical neurons used in the recordings were studied in some detail, and the expression levels of various GABAAR subunits were investigated by western blotting and RT-qPCR...
2017: PloS One
https://www.readbyqxmd.com/read/29028351/a-hexamer-of-a-peptide-derived-from-a%C3%AE-16-36
#11
Adam G Kreutzer, Ryan K Spencer, Kate J McKnelly, Stan Yoo, Imane L Hamza, Patrick J Salveson, James S Nowick
The absence of high-resolution structures of amyloid oligomers constitutes a major gap in our understanding of amyloid diseases. Increasing evidence indicates that oligomers of the β-amyloid peptide Aβ are especially important in the progression of Alzheimer's disease. In many Aβ oligomers, the Aβ monomer components are thought to adopt a β-hairpin conformation. This paper describes the design and study of a macrocyclic β-hairpin peptide derived from Aβ16-36. SDS-PAGE and size exclusion chromatography studies show that the Aβ16-36 β-hairpin peptide assembles in solution to form hexamers, trimers, and dimers...
October 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29028209/digital-implementation-of-the-two-compartmental-pinsky-rinzel-pyramidal-neuron-model
#12
Elahe Rahimian, Soheil Zabihi, Mahmood Amiri, Bernabe Linares-Barranco
It is believed that brain-like computing system can be achieved by the fusion of electronics and neuroscience. In this way, the optimized digital hardware implementation of neurons, primary units of nervous system, play a vital role in neuromorphic applications. Moreover, one of the main features of pyramidal neurons in cortical areas is bursting activities that has a critical role in synaptic plasticity. The Pinsky-Rinzel model is a nonlinear two-compartmental model for CA3 pyramidal cell that is widely used in neuroscience...
October 12, 2017: IEEE Transactions on Biomedical Circuits and Systems
https://www.readbyqxmd.com/read/29028183/non-synaptic-signaling-from-cerebellar-climbing-fibers-modulates-golgi-cell-activity
#13
Angela K Nietz, Jada H Vaden, Luke T Coddington, Linda Overstreet-Wadiche, Jacques I Wadiche
Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/29027981/bace1-function-and-inhibition-implications-of-intervention-in-the-amyloid-pathway-of-alzheimer-s-disease-pathology
#14
REVIEW
Gerald Koelsch
Alzheimer's disease (AD) is a fatal progressive neurodegenerative disorder characterized by increasing loss in memory, cognition, and function of daily living. Among the many pathologic events observed in the progression of AD, changes in amyloid β peptide (Aβ) metabolism proceed fastest, and precede clinical symptoms. BACE1 (β-secretase 1) catalyzes the initial cleavage of the amyloid precursor protein to generate Aβ. Therefore inhibition of BACE1 activity could block one of the earliest pathologic events in AD...
October 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29027929/procyanidin-b2-protects-neurons-from-oxidative-nitrosative-and-excitotoxic-stress
#15
Taylor C Sutcliffe, Aimee N Winter, Noelle C Punessen, Daniel A Linseman
The aberrant generation of oxygen and nitrogen free radicals can cause severe damage to key cellular components, resulting in cell apoptosis. Similarly, excitotoxicity leads to protease activation and mitochondrial dysfunction, which subsequently causes cell death. Each of these factors play critical roles in the neuronal cell death underlying various neurodegenerative diseases. Procyanidin B2 (PB2) is a naturally occurring polyphenolic compound found in high concentrations in cocoa, apples, and grapes. Here, we examine the neuroprotective effects of PB2 in primary cultures of rat cerebellar granule neurons (CGNs) exposed to various stressors...
October 13, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-cav-channels
#16
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low-voltage activated (LVA, CaV3.1-3.3)...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29027903/functional-dichotomy-in-spinal-vs-prefrontal-projecting-locus-coeruleus-modules-splits-descending-noradrenergic-analgesia-from-ascending-aversion-and-anxiety-in-rats
#17
Stefan Hirschberg, Yong Li, Andrew Randall, Eric J Kremer, Anthony E Pickering
The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not known whether they can act independently of ascending LC projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in LC neurons with spinal (LC:(SC)) or prefrontal cortex (LC:(PFC)) projections...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/29027727/downregulated-apoptosis-and-autophagy-after-anti-a%C3%AE-immunotherapy-in-alzheimer-s-disease
#18
Claire Paquet, James Ar Nicoll, Seth Love, François Mouton-Liger, Clive Holmes, Jacques Hugon, Delphine Boche
Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35...
October 13, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29027701/cellular-and-molecular-characterization-of-idh1-mutated-diffuse-low-grade-gliomas-reveals-tumor-heterogeneity-and-absence-of-egfr-pdgfr%C3%AE-activation
#19
S Azar, N Leventoux, C Ripoll, V Rigau, C Gozé, F Lorcy, L Bauchet, H Duffau, P O Guichet, B Rothhut, J P Hugnot
Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment...
October 13, 2017: Glia
https://www.readbyqxmd.com/read/29027613/both-decreased-akt-expression-and-mtor-phosphorylation-are-related-to-decreased-neuronal-differentiation-in-the-hippocampal-alveus-of-aged-mice
#20
Bing Chun Yan, Dan Jiang, Jie Wang, Yuanyuan Zhang, Xiaolu Zhu, Pei Xu, Xing Yu, Moo-Ho Won, Pei Qing Su
BACKGROUND: Aging is an inevitable process which results in many changes. These changes are closely related to the hippocampus which is in charge of long-term learning and episodic memory. AIM: This study was to investigate age-related changes of the cell proliferation, neuroblast differentiation and Akt/mTOR signaling in the hippocampal alveus of aged mice. METHODS: In the present study, we compared the differences of neurogenesis in the hippocampal alveus between adult (postnatal month 6) and aged (postnatal month 24) mice using immunohistochemistry and western blot analysis...
October 13, 2017: Aging Clinical and Experimental Research
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