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https://www.readbyqxmd.com/read/29451229/m-aaa-proteases-mitochondrial-calcium-homeostasis-and-neurodegeneration
#1
REVIEW
Maria Patron, Hans-Georg Sprenger, Thomas Langer
The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected...
February 16, 2018: Cell Research
https://www.readbyqxmd.com/read/29449528/als-related-human-cortical-and-motor-neurons-survival-is-differentially-affected-by-sema3a
#2
Anastasya Birger, Miri Ottolenghi, Liat Perez, Benjamin Reubinoff, Oded Behar
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by cell death of upper and lower motor neurons (MNs). The cause of MN cell loss is not completely understood but involves both cell autonomous and non-cell autonomous mechanisms. Numerous molecules have been implicated to be involved in the death of MNs. One such candidate is semaphorin 3A (Sema3A). In ALS patients, Sema3A was shown to be significantly upregulated in the motor cortex and downregulated in the spinal cord. In the mouse, Sema3A was shown to be an axon repellent molecule for MNs...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445326/structure-function-studies-of-the-%C3%AE-4-subunit-reveal-evolutionary-loss-of-a-glyr-subtype-involved-in-startle-and-escape-responses
#3
Sophie Leacock, Parnayan Syed, Victoria M James, Anna Bode, Koichi Kawakami, Angelo Keramidas, Maximiliano Suster, Joseph W Lynch, Robert J Harvey
Inhibitory glycine receptors (GlyRs) are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1), cortical neuronal migration/autism spectrum disorder (GlyR α2), and inflammatory pain sensitization/rhythmic breathing (GlyR α3). However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene ( GLRA4 ) is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4). Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29444083/high-fat-diet-sensitizes-fibromyalgia-like-pain-behaviors-in-mice-via-tumor-necrosis-factor-alpha
#4
Dan Tian, Miao Tian, Leilei Zhang, Peng Zhao, Yunfeng Cui, Jinlong Li
Fibromyalgia (FM) and obesity are closely related. However, little is known about how obesity contributes to FM. Importantly, adequate evidence has shown that tumor necrosis factor alpha (TNF-α) plays a critical role in obesity. Thus, we hypothesized that obesity-induced TNF-α release may potentiate FM-associated pain. To test this hypothesis, we investigated the role of TNF-α in the development of FM-like pain in a mouse model of acid saline injection-induced FM. Consistent with previous reports, we showed that repeated acid saline injections induced bilateral mechanical hyperalgesia, and this effect lasted for at least 4 days after acid saline injections...
2018: PloS One
https://www.readbyqxmd.com/read/29440992/the-bcl-2-homology-3-domain-bh3-only-proteins-bid-dp5-hrk-and-bnip3l-are-upregulated-in-reactive-astrocytes-of-end-stage-mutant-sod1-mouse-spinal-cord
#5
Nathan Duval, Whitney A Sumner, Anna G Andrianakos, Josie J Gray, Ron J Bouchard, Heather M Wilkins, Daniel A Linseman
The molecular mechanisms leading to motor neuron death in amyotrophic lateral sclerosis (ALS) are unknown; however, several studies have provided evidence of a central role for intrinsic apoptosis. Bcl-2 homology-3 domain (BH3)-only proteins are pro-apoptotic members of the Bcl-2 family whose enhanced expression acts as a trigger for the intrinsic apoptotic cascade. Here, we compared the relative expression of BH3-only proteins in the spinal cord of end-stage G93A mutant SOD1 mice to age-matched wild-type (WT) mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29432416/sox2-regulates-common-and-specific-stem-cell-features-in-the-cns-and-endoderm-derived-organs
#6
Daniel W Hagey, Susanne Klum, Idha Kurtsdotter, Cecile Zaouter, Danijal Topcic, Olov Andersson, Maria Bergsland, Jonas Muhr
Stem cells are defined by their capacities to self-renew and generate progeny of multiple lineages. The transcription factor SOX2 has key roles in the regulation of stem cell characteristics, but whether SOX2 achieves these functions through similar mechanisms in distinct stem cell populations is not known. To address this question, we performed RNA-seq and SOX2 ChIP-seq on embryonic mouse cortex, spinal cord, stomach and lung/esophagus. We demonstrate that, although SOX2 binds a similar motif in the different cell types, its target regions are primarily cell-type-specific and enriched for the distinct binding motifs of appropriately expressed interacting co-factors...
February 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29430855/dynorphinergic-system-alterations-in-the-corticostriatal-circuitry-of-neuropathic-mice-supports-its-role-in-the-negative-affective-component-of-pain
#7
Palmisano Martina, Caputi Francesca Felicia, Mercatelli Daniela, Romualdi Patrizia, Candeletti Sanzio
The dynorphinergic system is involved in pain transmission at spinal level, where dynorphin exerts antinociceptive or pronociceptive effects, based on its opioid or non-opioid actions. Surprisingly, little evidence is currently available concerning the supraspinal role of the dynorphinergic system in pain conditions. The present study aimed to investigate whether neuropathic pain is accompanied by prodynorphin (Pdyn) and κ-opioid receptor (Oprk1) gene expression alterations in selected mouse brain areas. To this end, mice were subjected to chronic constriction injury of the right sciatic nerve and neuropathic pain behavioral signs were ascertained after 14 days...
February 12, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29425965/the-small-heat-shock-proteins-especially-hspb4-and-hspb5-are-promising-protectants-in-neurodegenerative-diseases
#8
REVIEW
Zhihui Zhu, Georg Reiser
Small heat shock proteins (sHsps) are a group of proteins with molecular mass between 12 and 43 kDa. Currently, 11 members of this family have been classified, namely HspB1 to HspB11. HspB1, HspB2, HspB5, HspB6, HspB7, and HspB8, which are expressed in brain have been observed to be related to the pathology of neurodegenerative diseases, including Parkinson's, Alzheimer's, Alexander's disease, multiple sclerosis, and human immunodeficiency virus-associated dementia. Specifically, sHsps interact with misfolding and damaging protein aggregates, like Glial fibrillary acidic protein in AxD, β-amyloid peptides aggregates in Alzheimer's disease, Superoxide dismutase 1 in Amyotrophic lateral sclerosis and cytosine-adenine-guanine/polyglutamine (CAG/PolyQ) in Huntington's disease, Spinocerebellar ataxia type 3, Spinal-bulbar muscular atrophy, to reduce the toxicity or increase the clearance of these protein aggregates...
February 6, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29424035/involvement-of-spinal-cannabinoid-receptors-in-the-antipruritic-effects-of-win-55-212-2-a-cannabinoid-receptor-agonist
#9
K A Bilir, G Anli, E Ozkan, O Gunduz, A Ulugol
BACKGROUND: Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids. AIM: To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2...
February 9, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29416499/a-metadata-analysis-of-oxidative-stress-etiology-in-preclinical-amyotrophic-lateral-sclerosis-benefits-of-antioxidant-therapy
#10
Leila Bond, Kamren Bernhardt, Priyank Madria, Katherine Sorrentino, Hailee Scelsi, Cassie S Mitchell
Oxidative stress, induced by an imbalance of free radicals, incites neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). In fact, a mutation in antioxidant enzyme superoxide dismutase 1 (SOD1) accounts for 20% of familial ALS cases. However, the variance among individual studies examining ALS oxidative stress clouds corresponding conclusions. Therefore, we construct a comprehensive, temporal view of oxidative stress and corresponding antioxidant therapy in preclinical ALS by mining published quantitative experimental data and performing metadata analysis of 41 studies...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29408351/in-vivo-two-photon-imaging-of-motoneurons-and-adjacent-glia-in-the-ventral-spinal-cord
#11
Luciana Politti Cartarozzi, Phillip Rieder, Xianshu Bai, Anja Scheller, Alexandre Leite Rodrigues de Oliveira, Frank Kirchhoff
BACKGROUND: Interactions between motoneurons and glial cells are pivotal to regulate and maintain functional states and synaptic connectivity in the spinal cord. In vivo two-photon imaging of the nervous system provided novel and unexpected knowledge about structural and physiological changes in the grey matter of the forebrain and in the dorsal white matter of the spinal cord. NEW METHOD: Here, we describe a novel experimental strategy to investigate the spinal grey matter, i...
February 3, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29407767/involvement-of-glycine-receptor-%C3%AE-1-subunits-in-cannabinoid-induced-analgesia
#12
Jieping Lu, Sijia Fan, Guichang Zou, Yiwen Hou, Tao Pan, Weiwei Guo, Lei Yao, Feng Du, Gregg E Homanics, Dan Liu, Li Zhang, Wei Xiong
Some cannabinoids have been shown to suppress chronic pain by targeting glycine receptors (GlyRs). Although cannabinoid potentiation of α3 GlyRs is thought to contribute to cannabinoid-induced analgesia, the role of cannabinoid potentiation of α1 GlyRs in cannabinoid suppression of chronic pain remains unclear. Here we report that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, significantly suppresses chronic inflammatory pain caused by noxious heat stimulation. This effect may involve spinal α1 GlyRs since the expression level of α1 subunits in the spinal cord is positively correlated with CFA-induced inflammatory pain and the GlyRs antagonist strychnine blocks the DH-CBD-induced analgesia...
February 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29406831/contribution-of-spinal-5-ht5a-receptors-to-the-antinociceptive-effects-of-systemically-administered-cannabinoid-agonist-win-55-212-2-and-morphine
#13
Ahmet Goktan Aksu, Ozgur Gunduz, Ahmet Ulugol
The antinociceptive effects of cannabinoids and opioids have been known for centuries. Serotonin and its receptors are also known to play important roles in nociception. However, the contribution of spinal 5-HT5A receptors in antinociceptive effects of cannabinoids and opioids has not been studied. We conducted this study to clarify spinal mechanisms of the actions of the antinociceptive effects of cannabinoids and opioids. Hot-plate and tail-flick tests were used to assess the antinociceptive activity in Balb/c mice...
February 6, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29405035/protective-effects-of-long-term-lithium-administration-in-a-slowly-progressive-sma-mouse-model
#14
Francesca Biagioni, Michela Ferrucci, Larisa Ryskalin, Federica Fulceri, Gloria Lazzeri, Maria Teresa Calierno, Carla L Busceti, Riccardo Ruffoli, Francesco Fornai
In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course...
December 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29402411/epigallocatechin-3-gallate-attenuates-acute-and-chronic-psoriatic-itch-in-mice-involvement-of-antioxidant-anti-inflammatory-effects-and-suppression-of-erk-and-akt-signaling-pathways
#15
Ran Guo, Feng-Ming Zhou, Cun-Jin Su, Teng-Teng Liu, Yan Zhou, Li Fan, Zhi-Hong Wang, Xu Liu, Ya Huang, Tong Liu, Jianping Yang, Li-Hua Chen
Chronic itch is a distressing symptom of many skin diseases and negatively impacts quality of life. However, there is no medication for most forms of chronic itch, although antihistamines are often used for anti-itch treatment. Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, exhibits anti-oxidative and anti-inflammatory properties. Our previous studies highlighted a key role of oxidative stress and proinflammatory cytokines in acute and chronic itch. Here, we evaluated the effects of green tea polyphenon 60 and EGCG on acute and chronic itch in mouse models and explored its potential mechanisms...
February 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29402285/-18-f-vc701-pet-and-mri-in-the-in-vivo-neuroinflammation-assessment-of-a-mouse-model-of-multiple-sclerosis
#16
Sara Belloli, Lucia Zanotti, Valentina Murtaj, Cristina Mazzon, Giuseppe Di Grigoli, Cristina Monterisi, Valeria Masiello, Leonardo Iaccarino, Andrea Cappelli, Pietro Luigi Poliani, Letterio Salvatore Politi, Rosa Maria Moresco
BACKGROUND: Positron emission tomography (PET) using translocator protein (TSPO) ligands has been used to detect neuroinflammatory processes in neurological disorders, including multiple sclerosis (MS). The aim of this study was to evaluate neuroinflammation in a mouse MS model (EAE) using TSPO-PET with18 F-VC701, in combination with magnetic resonance imaging (MRI). METHODS: MOG35-55 /CFA and pertussis toxin protocol was used to induce EAE in C57BL/6 mice. Disease progression was monitored daily, whereas MRI evaluation was performed at 1, 2, and 4 weeks post-induction...
February 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29395120/blockage-of-spinal-endothelin-a-receptors-attenuates-bone-cancer-pain-via-regulation-of-the-akt-erk-signaling-pathway-in-mice
#17
Ming-Ming Han, Cheng-Wei Yang, Chi-Wai Cheung, Juan Li
Bone cancer pain (BCP) is a common source of pain in patients with advanced stage and metastatic cancer; however, existing treatment for this kind of pain remains deficient. Being closely related to sensory change and inflammatory pain in both the central and peripheral nervous systems, endothelin A receptor (ETAR) plays an essential role in pain processing. As a result, ETAR antagonist has been reported to alleviate both neuropathic and inflammatory pain. Thus far, the role of ETAR in the process of BCP is still ambiguous...
January 26, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29394509/increase-of-hcn-current-in-the-aberrant-excitability-of-spinal-muscular-atrophy
#18
Hsing-Jung Lai, Chien-Lin Chen, Li-Kai Tsai
Objective The pathophysiology of spinal muscular atrophy (SMA) is still unclear. Methods The nerve excitability test in SMA patients and a mouse model of SMA was carried out to explore the pathophysiology of nodal and internodal currents, and quantitative PCR, Western blotting and whole-cell patch-clamp recording were used for the identified hypothesis. Results The nerve excitability test in SMA patients showed increased inward rectification in the current-threshold relationship and increased overshoot after hyperpolarizing threshold electrotonus, which indicates increased hyperpolarization-activated cyclic nucleotide-gated (HCN) current; these findings correlated with disease severity...
February 2, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29394243/effects-of-ovariectomy-in-an-hsod1-g93a-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis-als
#19
Lina Yan, Yaling Liu, Can Sun, Qian Zheng, Pengli Hao, Jingxu Zhai, Yuanyuan Liu
BACKGROUND Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive muscular dystrophy and paralysis; most ALS patients die from respiratory failure within 3 to 5 years, and there is currently no effective treatment. Some studies have indicated sex differences in the incidence of ALS, and evidence suggests a neuroprotective role for estrogen. MATERIAL AND METHODS We used human Cu/Zn superoxide dismutase (hSOD1-G93A) transgenic mice to determine the effects of ovariotomy on the onset of disease and behavior; we also used Western blotting to measure the expression of aromatase and estrogen receptors, as well as the inflammatory cytokines and apoptosis markers, in the lumbar spinal cord to determine the mechanism of estrogen-mediated neuroprotection...
February 2, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29391529/small-molecule-flunarizine-increases-smn-protein-in-nuclear-cajal-bodies-and-motor-function-in-a-mouse-model-of-spinal-muscular-atrophy
#20
Delphine Sapaly, Matthieu Dos Santos, Perrine Delers, Olivier Biondi, Gwendoline Quérol, Léo Houdebine, Kevinee Khoobarry, François Girardet, Philippe Burlet, Anne-Sophie Armand, Christophe Chanoine, Jean-François Bureau, Frédéric Charbonnier, Suzie Lefebvre
The hereditary neurodegenerative disorder spinal muscular atrophy (SMA) is characterized by the loss of spinal cord motor neurons and skeletal muscle atrophy. SMA is caused by mutations of the survival motor neuron (SMN) gene leading to a decrease in SMN protein levels. The SMN deficiency alters nuclear body formation and whether it can contribute to the disease remains unclear. Here we screen a series of small-molecules on SMA patient fibroblasts and identify flunarizine that accumulates SMN into Cajal bodies, the nuclear bodies important for the spliceosomal small nuclear RNA (snRNA)-ribonucleoprotein biogenesis...
February 1, 2018: Scientific Reports
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