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Experimental Neurology

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https://www.readbyqxmd.com/read/27894788/neurotoxic-mechanisms-of-paclitaxel-are-local-to-the-distal-axon-and-independent-of-transport-defects
#1
Erica L Gornstein, Thomas L Schwarz
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of paclitaxel and other chemotherapeutic agents. Paclitaxel binds and stabilizes microtubules, but the cellular mechanisms that underlie paclitaxel's neurotoxic effects are not well understood. We therefore used primary cultures of adult murine dorsal root ganglion neurons, the cell type affected in patients, to examine leading hypotheses to explain paclitaxel neurotoxicity. We address the role of microtubule hyperstabilization and its downstream effects...
November 26, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27889468/mitochondrial-cristae-remodelling-is-associated-with-disrupted-opa1-oligomerisation-in-the-huntington-s-disease-r6-2-fragment-model
#2
Tanja Hering, Kerstin Kojer, Nathalie Birth, Jaqueline Hallitsch, Jan-Willem Taanman, Michael Orth
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27889467/treadmill-exercise-decreases-amyloid-%C3%AE-burden-possibly-via-activation-of-sirt-1-signaling-in-a-mouse-model-of-alzheimer-s-disease
#3
Jung-Hoon Koo, Eun-Bum Kang, Yoo-Sung Oh, Dae-Seung Yang, Joon-Yong Cho
Accumulation of amyloid-β (Aβ) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces Aβ levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aβ production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RARβ, ultimately facilitating the non-amyloidogenic pathway...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27865736/ips-derived-neural-progenitor-cells-from-ppms-patients-reveal-defect-in-myelin-injury-response
#4
Alexandra M Nicaise, Erin Banda, Rosa M Guzzo, Kristen Russomanno, Wanda Castro-Borrero, Cory M Willis, Kasey M Johnson, Albert C Lo, Stephen J Crocker
Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) currently lacking any effective treatment. Promoting endogenous brain repair offers a potential strategy to halt and possibly restore neurologic function in PPMS. To understand how the microenvironment within white matter lesions plays a role in repair we have focused on neural progenitor cells (NPCs) since these are found in lesions in PPMS and have been found to influence oligodendrocyte progenitor cell maturation (OPCs)...
November 16, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27856287/the-inhibition-of-spinal-synaptic-plasticity-mediated-by-activation-of-amp-activated-protein-kinase-signaling-alleviates-the-acute-pain-induced-by-oxaliplatin
#5
Yun-Zhi Ling, Zhen-Yu Li, Han-Dong Ou-Yang, Chao Ma, Shao-Ling Wu, Jia-You Wei, Huan-Huan Ding, Xiao-Long Zhang, Meng Liu, Cui-Cui Liu, Zhen-Zhen Huang, Wen-Jun Xin
Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg)...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27856286/nox4-is-an-early-initiator-of-neuropathic-pain
#6
Christian Geis, Eva Geuss, Claudia Sommer, Harald H H W Schmidt, Christoph Kleinschnitz
Treatment of neuropathic pain remains challenging as the etiology is heterogeneous and pathomechanisms are incompletely understood. One possible mechanism is oxidative stress due to unphysiological reactive oxygen species (ROS) formation. The only know dedicated enzymatic source of ROS are NADPH oxidases of which the type 4 isoform (NOX4) has been suggested to be involved in the subacute and chronic phase of neuropathic pain. Here, we aim to translate this finding into a treatment strategy by examining the efficacy of the NOX1/4-specific inhibitor GKT136901 using the chronic constriction injury (CCI) mouse model of neuropathic pain...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27856285/neurotrophic-and-neuroprotective-effects-of-oxyntomodulin-in-neuronal-cells-and-a-rat-model-of-stroke
#7
Yazhou Li, Kou-Jen Wu, Seong-Jin Yu, Ian A Tamargo, Yun Wang, Nigel H Greig
Proglucagon-derived peptides, especially glucagon-like peptide-1 (GLP-1) and its long-acting mimetics, have exhibited neuroprotective effects in animal models of stroke. Several of these peptides are in clinical trials for stroke. Oxyntomodulin (OXM) is a proglucagon-derived peptide that co-activates the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). The neuroprotective action of OXM, however, has not been thoroughly investigated. In this study, the neuroprotective effect of OXM was first examined in human neuroblastoma (SH-SY5Y) cells and rat primary cortical neurons...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27851902/therapeutic-potential-of-mesenchymal-stem-cells-for-the-treatment-of-diabetic-peripheral-neuropathy
#8
Marianna Monfrini, Elisabetta Donzelli, Virginia Rodriguez-Menendez, Elisa Ballarini, Valentina Alda Carozzi, Alessia Chiorazzi, Cristina Meregalli, Annalisa Canta, Norberto Oggioni, Luca Crippa, Federica Avezza, Sara Silvani, Barbara Bonandrini, Marina Figliuzzi, Andrea Remuzzi, Carla Porretta-Serapiglia, Roberto Bianchi, Giuseppe Lauria, Giovanni Tredici, Guido Cavaletti, Arianna Scuteri
Type-1 Diabetes is generally treated with exogenous insulin administration. Despite treatment, a very common long term consequence of diabetes is the development of a disabling and painful peripheral neuropathy. The transplantation of pancreatic islets is an advanced alternative therapeutic approach, but its clinical application is still very limited, mainly because of the great number of islets required to complete the procedure and of their short-term survival. An intriguing method to improve the performance of pancreatic islets transplantation is the co-transplantation of Mesenchymal Stem Cells (MSCs), adult stem cells already known to support the survival of different cellular populations...
November 13, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27845037/novel-glp-1r-gipr-co-agonist-twincretin-is-neuroprotective-in-cell-and-rodent-models-of-mild-traumatic-brain-injury
#9
Ian A Tamargo, Miaad Bader, Yazhou Li, Seong-Jin Yu, Yun Wang, Konrad Talbot, Richard D DiMarchi, Chaim G Pick, Nigel H Greig
Several single incretin receptor agonists that are approved for the treatment of type 2 diabetes mellitus (T2DM) have been shown to be neuroprotective in cell and animal models of neurodegeneration. Recently, a synthetic dual incretin receptor agonist, nicknamed "twincretin," was shown to improve upon the metabolic benefits of single receptor agonists in mouse and monkey models of T2DM. In the current study, the neuroprotective effects of twincretin are probed in cell and mouse models of mild traumatic brain injury (mTBI), a prevalent cause of neurodegeneration in toddlers, teenagers and the elderly...
November 11, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27840071/inward-rectifier-k-channel-and-t-type-ca-2-channel-contribute-to-enhancement-of-gabaergic-transmission-induced-by-%C3%AE-1-adrenoceptor-in-the-prefrontal-cortex
#10
Fei Luo, Jian Zheng, Xuan Sun, Hua Tang
The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α1, α2, β1 or β2-adrenoceptor. Our recent study has revealed that β1-adrenoceptor (β1-AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β1-AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β1-AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats...
November 11, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27836728/altered-gene-expression-profile-in-a-mouse-model-of-scn8a-encephalopathy
#11
Ryan S Sprissler, Jacy L Wagnon, Rosie K Bunton-Stasyshyn, Miriam H Meisler, Michael F Hammer
SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures...
November 9, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27823926/cisplatin-induced-neuropathic-pain-is-mediated-by-upregulation-of-n-type-voltage-gated-calcium-channels-in-dorsal-root-ganglion-neurons
#12
Markus Leo, Linda-Isabell Schmitt, Martin Erkel, Margarita Melnikova, Jürgen Thomale, Tim Hagenacker
Cisplatin is important in the treatment of various types of cancer. Although it is highly effective, it also has severe side effects, with neurotoxicity in dorsal root ganglion (DRG) neurons being one of the most common. The key mechanisms of neurotoxicity are still controversially discussed; however, disturbances of the calcium homeostasis in DRG neurons have been suggested to mediate cisplatin neurotoxicity. By using the whole-cell patch-clamp technique, immunostaining and behavioral experiments with Sprague-Dawley rats, we examined the influence of short- and long-term exposure to cisplatin on voltage-gated calcium channel (VGCC) currents (ICa(V)) in small DRG neurons...
November 5, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27818188/complete-spinal-cord-injury-sci-transforms-how-brain-derived-neurotrophic-factor-bdnf-affects-nociceptive-sensitization
#13
Yung-Jen Huang, Kuan H Lee, James W Grau
Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF...
November 3, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27794423/neuroprotective-effect-of-lercanidipine-in-middle-cerebral-artery-occlusion-model-of-stroke-in-rats
#14
Sangeetha Gupta, Uma Sharma, Naranamangalam R Jagannathan, Yogendra Kumar Gupta
Oxidative stress, inflammation and apoptotic neuronal cell death are cardinal mechanisms involved in the cascade of acute ischemic stroke. Lercanidipine apart from calcium channel blocking activity possesses anti-oxidant, anti-inflammatory and anti-apoptotic properties. In the present study, we investigated neuroprotective efficacy and therapeutic time window of lercanidipine in a 2h middle cerebral artery occlusion (MCAo) model in male Wistar rats. The study design included: acute (pre-treatment and post-treatment) and sub-acute studies...
October 26, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27776252/the-role-of-spinal-interleukin-1%C3%AE-and-astrocyte-connexin-43-in-the-development-of-mirror-image-pain-in-an-inflammatory-pain-model
#15
Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27773720/the-role-of-spinal-interleukin-1%C3%AE-and-astrocyte-connexin-43-in-the-development-of-mirror-image-pain-in-an-inflammatory-pain-model
#16
Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27771352/functional-alterations-of-the-dopaminergic-and-glutamatergic-systems-in-spontaneous-%C3%AE-synuclein-overexpressing-rats
#17
Ezia Guatteo, Francesca Romana Rizzo, Mauro Federici, Alberto Cordella, Ada Ledonne, Laura Latini, Annalisa Nobili, Maria Teresa Viscomi, Filippo Biamonte, Kerstin K Landrock, Alessandro Martini, Daniela Aversa, Chiara Schepisi, Marcello D'Amelio, Nicola Berretta, Nicola B Mercuri
The presence of α-synuclein (α-syn) in Lewy bodies and Lewy neurites is an important characteristic of the neurodegenerative processes of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons in Parkinson's disease (PD) and other synucleinopathies. Here we report that Berlin-Druckrey rats carrying a spontaneous mutation in the 3' untranslated region of α-syn mRNA (m/m rats) display a marked accumulation of α-syn in the mesencephalic area, striatum and frontal cortex, accompanied to severe dysfunctions in the dorsolateral striatum...
October 20, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27771354/paradoxical-lower-sensitivity-of-locus-coeruleus-than-substantia-nigra-pars-compacta-neurons-to-acute-actions-of-rotenone
#18
Andrew G Yee, Peter S Freestone, Ji-Zhong Bai, Janusz Lipski
Parkinson's disease (PD) is not only associated with degeneration of dopaminergic (DAergic) neurons in the Substantia Nigra, but also with profound loss of noradrenergic neurons in the Locus Coeruleus (LC). Remarkably, LC degeneration may exceed, or even precede the loss of nigral DAergic neurons, suggesting that LC neurons may be more susceptible to damage by various insults. Using a combination of electrophysiology, fluorescence imaging and electrochemistry, we directly compared the responses of LC, nigral DAergic and nigral non-dopaminergic (non-DAergic) neurons in rat brain slices to acute application of rotenone, a mitochondrial toxin used to create animal and in vitro models of PD...
October 19, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27771353/g-csf-treatment-promotes-apoptosis-of-autoreactive-t-cells-to-restrict-the-inflammatory-cascade-and-accelerate-recovery-in-experimental-allergic-encephalomyelitis
#19
Wei Peng
G-CSF is a hematopoietic growth factor that regulates the proliferation, differentiation and survival of myeloid lineage cells, which has protective effects in autoimmune neuroinflammatory diseases such as EAE. Here we use EAE model treated by G-CSF to address the hypothesis that G-CSF inhibits the proliferative response of splenic T cells via the enhancement of apoptosis, and this priming effect of G-CSF depends on the cell cycle. Our results show that G-CSF administration reduced EAE frequency and severity of attacks...
October 19, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27769717/progressive-neuronal-activation-accompanies-epileptogenesis-caused-by-hippocampal-glutamine-synthetase-inhibition
#20
Benjamin Albright, Roni Dhaher, Helen Wang, Roa Harb, Tih-Shih W Lee, Hitten Zaveri, Tore Eid
Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE). However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats...
October 18, 2016: Experimental Neurology
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