Understanding resilience: New approaches for preventing and treating PTSD.
Abstract All individuals experience stressful life events, and up to 84% of the general population will experience at least one potentially traumatic event. In some cases, acute or chronic stressors lead to the development of posttraumatic stress disorder (PTSD) or other psychopathology; however, the majority of people are resilient to such effects. Resilience is the ability to adapt successfully in the face of stress and adversity. A wealth of research has begun to identify the genetic, epigenetic, neural, and environmental underpinnings of resilience, and has indicated that resilience is mediated by adaptive cha...
Source: Experimental Neurology - July 11, 2016 Category: Neurology Authors: Horn SR, Charney DS, Feder A Tags: Exp Neurol Source Type: research

Physiological cerebrovascular remodeling in response to chronic mild hypoxia: A role for activated protein C.
ner R Abstract Activated protein C (APC) is a serine protease that promotes favorable changes in vascular barrier integrity and post-ischemic angiogenic remodeling in animal models of ischemic stroke, and its efficacy is currently being investigated in clinical ischemic stroke trials. Interestingly, application of sub-clinical chronic mild hypoxia (CMH) (8% O2) also promotes angiogenic remodeling and increased tight junction protein expression, suggestive of enhanced blood-brain barrier (BBB) integrity, though the role of APC in mediating the influence of CMH has not been investigated. To examine this potential li...
Source: Experimental Neurology - July 10, 2016 Category: Neurology Authors: Burnier L, Boroujerdi A, Fernández JA, Welser-Alves JV, Griffin JH, Milner R Tags: Exp Neurol Source Type: research

Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures.
Abstract Temporal lobe epilepsy is the most common form of medically-intractable epilepsy. While seizures in TLE originate in structures such as hippocampus, amygdala, and temporal cortex, they propagate through a crucial relay: the midline/intralaminar thalamus. Prior studies have shown that pharmacological inhibition of midline thalamus attenuates limbic seizures. Here, we examined a recently developed technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), as a means of chemogenetic silencing to attenuate limbic seizures. Adult, male rats were electrically kindled from the amygdala, an...
Source: Experimental Neurology - July 9, 2016 Category: Neurology Authors: Wicker E, Forcelli PA Tags: Exp Neurol Source Type: research

Inhibiting cortical protein kinase a in spinal cord injured rats enhances efficacy of rehabilitative training.
In conclusion, blocking PKA in cortical neurons of spinal cord injured rats increases neurite outgrowth of the lesioned corticospinal tract fibres and the efficacy of rehabilitative training, likely via EPAC. PMID: 27401133 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - July 8, 2016 Category: Neurology Authors: Wei D, Hurd C, Galleguillos D, Singh J, Fenrich KK, Webber CA, Sipione S, Fouad K Tags: Exp Neurol Source Type: research

A mouse model for testing remyelinating therapies.
Abstract Used in combination with immunomodulatory therapies, remyelinating therapies are a viable therapeutic approach for treating individuals with multiple sclerosis. Studies of postmortem MS brains identified greater remyelination in demyelinated cerebral cortex than in demyelinated brain white matter and implicated reactive astrocytes as an inhibitor of white matter remyelination. An animal model that recapitulates these phenotypes would benefit the development of remyelination therapeutics. We have used a modified cuprizone protocol that causes a consistent and robust demyelination of mouse white matter and ...
Source: Experimental Neurology - July 3, 2016 Category: Neurology Authors: Bai CB, Sun S, Roholt A, Benson E, Edberg D, Medicetty S, Dutta R, Kidd G, Macklin WB, Trapp B Tags: Exp Neurol Source Type: research

Corticosterone dysregulation exacerbates disease progression in the R6/2 transgenic mouse model of Huntington's disease.
Abstract Huntington's disease (HD) is a genetic neurological disorder that causes severe and progressive motor, cognitive, psychiatric, and metabolic symptoms. There is a robust, significant elevation in circulating levels of the stress hormone, cortisol, in HD patients; however, the causes and consequences of this elevation are largely uncharacterized. Here, we evaluated whether elevated levels of corticosterone, the rodent homolog of cortisol, contributed to the development of symptomology in transgenic HD mice. Wild-type (WT) and transgenic R6/2 mice were given either 1) adrenalectomy with WT-level corticostero...
Source: Experimental Neurology - July 2, 2016 Category: Neurology Authors: Dufour BD, McBride JL Tags: Exp Neurol Source Type: research

Neuromodulation of the neural circuits controlling the lower urinary tract.
Abstract The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats.Here...
Source: Experimental Neurology - July 2, 2016 Category: Neurology Authors: Gad PN, Roy RR, Zhong H, Gerasimenko YP, Taccola G, Edgerton VR Tags: Exp Neurol Source Type: research

Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update.
Abstract Posttraumatic stress disorder (PTSD) is a trauma-evoked syndrome, with variable prevalence within the human population due to individual differences in coping and resiliency. In this review, we discuss evidence supporting the relevance of neuropeptide Y (NPY), a stress regulatory transmitter in PTSD. We consolidate findings from preclinical, clinical, and translational studies of NPY that are of relevance to PTSD with an attempt to provide a current update of this area of research. NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors. Studies in ...
Source: Experimental Neurology - July 1, 2016 Category: Neurology Authors: Schmeltzer SN, Herman JP, Sah R Tags: Exp Neurol Source Type: research

Autophagy modulators regulate survival motor neuron protein stability in motoneurons.
er RM PMID: 27373203 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 30, 2016 Category: Neurology Authors: Periyakaruppiah A, de la Fuente S, Arumugam S, Bahí N, Garcera A, Soler RM Tags: Exp Neurol Source Type: research

Subthalamic deep brain stimulation alters neuronal firing in canonical pain nuclei in a 6-hydroxydopamine lesioned rat model of Parkinson's disease.
We examined unilateral medial forebrain bundle 6-hydroxydopamine (6OHDA) rat model of PD to determine whether STN DBS alters neuronal firing rates in brain areas involved in ascending and descending pain processing. Specifically, single unit in vivo recordings were conducted in the anterior cingulate cortex (ACC), the periaqueductal grey (PAG), and the ventral posteriolateral nucleus of the thalamus (VPL), before, during and after stimulation was applied to the STN at 50 or 150Hz. RESULTS: Sham and 6OHDA lesioned animals have similar neuronal firing activity in the VPL, ACC and PAG before stimulation was applied (p>...
Source: Experimental Neurology - June 30, 2016 Category: Neurology Authors: Gee LE, Walling I, Ramirez-Zamora A, Shin DS, Pilitsis JG Tags: Exp Neurol Source Type: research

Pseudophosphorylation of tau at S422 enhances SDS-stable dimer formation and impairs both anterograde and retrograde fast axonal transport.
This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. Taken together, these findings identify a novel mechanistic basis by which pS422 confers upon tau a toxic effect that may directly contribute to axonal dysfunction in AD and other tauopathies. PMID: 27373205 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 30, 2016 Category: Neurology Authors: Tiernan CT, Combs B, Cox K, Morfini G, Brady ST, Counts SE, Kanaan NM Tags: Exp Neurol Source Type: research

Rodent spinal cord injury models for studies of axon regeneration.
PMID: 27374113 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 29, 2016 Category: Neurology Authors: Steward O, Willenberg R Tags: Exp Neurol Source Type: research

Role of CA3 theta-modulated interneurons during the transition to spontaneous seizures abbreviated title: Theta-modulated interneurons and seizures.
Abstract Multiple studies have observed heterogeneous neuronal firing patterns as a local network transitions to spontaneous seizures. We demonstrated that separately examining interneurons and pyramidal cells during this transition in a rat model of temporal lobe epilepsy elucidates some of this heterogeneity. Recently, it was demonstrated that classifying cells into specific theta-related subtypes further clarified the heterogeneity. Moreover, changes in neuronal synchrony with the local field potential were identified and determined to be specific to interneurons during the transition to seizures.To extend our ...
Source: Experimental Neurology - June 25, 2016 Category: Neurology Authors: Karunakaran S, Grasse DW, Moxon KA Tags: Exp Neurol Source Type: research

Increased miR-132-3p expression is associated with chronic neuropathic pain.
Sorkin LS Abstract Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or p...
Source: Experimental Neurology - June 24, 2016 Category: Neurology Authors: Leinders M, Üçeyler N, Pritchard RA, Sommer C, Sorkin LS Tags: Exp Neurol Source Type: research

Dysferlin function in skeletal muscle: Possible pathological mechanisms and therapeutical targets in dysferlinopathies.
Caviedes P Abstract Mutations in the dysferlin gene are linked to a group of muscular dystrophies known as dysferlinopathies. These myopathies are characterized by progressive atrophy. Studies in muscle tissue from dysferlinopathy patients or dysferlin-deficient mice point out its importance in membrane repair. However, expression of dysferlin homologous proteins that restore sarcolemma repair function in dysferlinopathy animal models fail to arrest muscle wasting, therefore suggesting that dysferlin plays other critical roles in muscle function. In the present review, we discuss dysferlin functions in the skelet...
Source: Experimental Neurology - June 24, 2016 Category: Neurology Authors: Cárdenas AM, González-Jamett AM, Cea LA, Bevilacqua JA, Caviedes P Tags: Exp Neurol Source Type: research

Endogenous hypothermic response to hypoxia reduces brain injury: Implications for modeling hypoxic-ischemic encephalopathy and therapeutic hypothermia in neonatal mice.
Herz J Abstract Hypothermia treatment (HT) is the only formally endorsed treatment recommended for hypoxic-ischemic encephalopathy (HIE). However, its success in protecting against brain injury is limited with a number to treat of 7-8. The identification of the target mechanisms of HIE in combination with HT will help to explain ineffective therapy outcomes but also requires stable experimental models in order to establish further neuroprotective therapies. Despite clinical and experimental indications for an endogenous thermoregulatory response to HIE, the potential effects on HIE-induced brain injury have large...
Source: Experimental Neurology - June 24, 2016 Category: Neurology Authors: Reinboth BS, Köster C, Abberger H, Prager S, Bendix I, Felderhoff-Müser U, Herz J Tags: Exp Neurol Source Type: research

Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE.
Abstract Experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis produced by immunization with myelin oligodendrocyte glycoprotein (MOG) and adjuvants, results from profound T-cell mediated CNS demyelination. EAE is characterized by progressive, ascending motor dysfunction and symptoms of ongoing pain and hypersensitivity, in some cases preceding or concomitant with the motor deficits. In this regard, the EAE model mimics major features of multiple sclerosis, where a central neuropathic pain state is common. Although the latter condition is presumed to arise from a CNS loss of inhibito...
Source: Experimental Neurology - June 22, 2016 Category: Neurology Authors: Frezel N, Sohet F, Daneman R, Basbaum AI, Braz JM Tags: Exp Neurol Source Type: research

Transcriptomic analyses of genes and tissues in inherited sensory neuropathies.
Abstract Inherited sensory neuropathies are caused by mutations in genes affecting either primary afferent neurons, or the Schwann cells that myelinate them. Using RNA-Seq, we analyzed the transcriptome of human and rat DRG and peripheral nerve, which contain sensory neurons and Schwann cells, respectively. We subdivide inherited sensory neuropathies based on expression of the mutated gene in these tissues, as well as in mouse TRPV1 lineage DRG nociceptive neurons, and across 32 human tissues from the Human Protein Atlas. We propose that this comprehensive approach to neuropathy gene expression leads to better und...
Source: Experimental Neurology - June 22, 2016 Category: Neurology Authors: Sapio MR, Goswami SC, Gross JR, Mannes AJ, Iadarola MJ Tags: Exp Neurol Source Type: research

Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy.
Abstract Synucleinopathy is characterized by abnormal accumulation of misfolded α-synuclein (α-Syn)-positive cytoplasmic inclusions and by neurodegeneration and cognitive impairments, but the pathogenesis mechanism of synucleinopathy remains to be defined. Using a transmission model of synucleinopathy by intracerebral injection of preformed A53T α-Syn fibrils, we investigated whether aberrant adenosine A2A receptor (A2AR) signaling contributed to pathogenesis of synucleinopathy. We demonstrated that intra-hippocampal injection of preformed mutant α-Syn fibrils triggered a striking and selec...
Source: Experimental Neurology - June 21, 2016 Category: Neurology Authors: Hu Q, Ren X, Liu Y, Li Z, Zhang L, Chen X, He C, Chen JF Tags: Exp Neurol Source Type: research

Effects of onabotulinumtoxinA on cardiac function following intradetrusor injections.
In conclusion, onabotulinumtoxinA intradetrusor injections do not seem to affect resting state cardiac function. Short-term changes such as total power might rather result from natural cardio-vascular responses to the procedure itself (e.g. discomfort, stress). Further detailed investigations also under physical stress and repeated injections are necessary to fully exclude systemic cardiac side effects of onabotulinumtoxinA intradetrusor injections. PMID: 27342082 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 21, 2016 Category: Neurology Authors: Mehnert U, de Kort LM, Wöllner J, Kozomara M, van Koeveringe GA, Kessler TM Tags: Exp Neurol Source Type: research

Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides.
Abstract The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, conti...
Source: Experimental Neurology - June 21, 2016 Category: Neurology Authors: Girard B, Peterson A, Malley S, Vizzard MA Tags: Exp Neurol Source Type: research

The glial scar is more than just astrocytes.
PMID: 27328838 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 18, 2016 Category: Neurology Authors: Silver J Tags: Exp Neurol Source Type: research

Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells.
In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12h or 5d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10d after HI. HI (n=7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P
Source: Experimental Neurology - June 15, 2016 Category: Neurology Authors: Li J, Yawno T, Sutherland A, Loose J, Nitsos I, Bischof R, Castillo-Melendez M, McDonald CA, Wong FY, Jenkin G, Miller SL Tags: Exp Neurol Source Type: research

Extended therapeutic window of a novel peptide inhibitor of TRPM2 channels following focal cerebral ischemia.
CONCLUSIONS: These data demonstrate the development of a new peptide inhibitor of TRPM2 channels that provides protection from ischemic stroke in young adult and aged male animals with a clinically relevant therapeutic window. PMID: 27317297 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 14, 2016 Category: Neurology Authors: Shimizu T, Dietz RM, Cruz-Torres I, Strnad F, Garske AK, Moreno-Garcia M, Venna VR, Quillinan N, Herson PS Tags: Exp Neurol Source Type: research

Dopaminergic neurons.
CONCLUSION: Our study showed the smo receptor function is not required for the maturation and survival of DA neurons during late development, aging or under stress challenge. However, smo function has an influence on behavior in young adult mice and in responses of mice to a drug that modulates DA neurochemistry through regulation of gene expression in DA neurons. Since young adult DAT-smo ko mice show hyperactivity and altered response to a psychostimulant drug (METH), this may indicate the involvement of the shh pathway in the development of functional changes that manifest as alterations in DA pathway dynamics. PMI...
Source: Experimental Neurology - June 14, 2016 Category: Neurology Authors: Zhou X, Pace J, Filichia E, Lv T, Davis B, Hoffer B, Selman W, Luo Y Tags: Exp Neurol Source Type: research

Epidermal innervation as a tool to study human axonal regeneration and disease progression.
PMID: 27317299 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 14, 2016 Category: Neurology Authors: Khoshnoodi MA, Ebenezer GJ, Polydefkis M Tags: Exp Neurol Source Type: research

Upregulation of the cannabinoid CB2 receptor in environmental and viral inflammation-driven rat models of Parkinson's disease.
This study indicates that these models may be useful for further investigation of the CB2 receptor as a target for anti-inflammatory disease modification in Parkinson's disease. PMID: 27317300 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 14, 2016 Category: Neurology Authors: Concannon RM, Okine BN, Finn DP, Dowd E Tags: Exp Neurol Source Type: research

Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia.
Abstract Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.e. sensorimotor gating, as reflected by disrupted prepulse inhibition (PPI), and attentional selectivity, as reflected by disrupted latent inhibition (LI). In additio...
Source: Experimental Neurology - June 11, 2016 Category: Neurology Authors: Bikovsky L, Hadar R, Soto-Montenegro ML, Klein J, Weiner I, Desco M, Pascau J, Winter C, Hamani C Tags: Exp Neurol Source Type: research

Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model.
CONCLUSION: ICH-induced PDGF-D accumulation contributed to post-ICH inflammation via PDGFR activation and enhanced macrophage infiltration. The inhibition of PDGFR had an anti-inflammatory effect. Plasmin is a possible upstream effector of PDGF-D. The targeting of PDGF-D may provide a novel way to decrease brain injury after ICH. PMID: 27302678 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 11, 2016 Category: Neurology Authors: Yang P, Manaenko A, Xu F, Miao L, Wang G, Hu X, Guo ZN, Hu Q, Hartman RE, Pearce WJ, Obenaus A, Zhang JH, Chen G, Tang J Tags: Exp Neurol Source Type: research

Intraspinal transplantation of subventricular zone-derived neural progenitor cells improves phrenic motor output after high cervical spinal cord injury.
Abstract Following spinal cord injury (SCI), intraspinal transplantation of neural progenitor cells (NPCs) harvested from the forebrain sub-ventricular zone (SVZ) can improve locomotor outcomes. Cervical SCI often results in respiratory-related impairments, and here we used an established model cervical SCI (C2 hemisection, C2Hx) to confirm the feasibility of mid-cervical transplantation of SVZ-derived NPCs and the hypothesis that that this procedure would improve spontaneous respiratory motor recovery. NPCs were isolated from the SVZ of enhanced green fluorescent protein (GFP) expressing neonatal rats, and then i...
Source: Experimental Neurology - June 11, 2016 Category: Neurology Authors: Sandhu MS, Ross HH, Lee KZ, Ormerod BK, Reier PJ, Fuller DD Tags: Exp Neurol Source Type: research

Targeting Kv1.3 channels to reduce white matter pathology after traumatic brain injury.
Abstract Axonal injury is present in essentially all clinically significant cases of traumatic brain injury (TBI). While no effective treatment has been identified to date, experimental TBI models have shown promising axonal protection using immunosuppressants FK506 and Cyclosporine-A, with treatment benefits attributed to calcineurin inhibition or protection of mitochondrial function. However, growing evidence suggests neuroprotective efficacy of these compounds may also involve direct modulation of ion channels, and in particular Kv1.3. The present study tested whether blockade of Kv1.3 channels, using Clofazimi...
Source: Experimental Neurology - June 11, 2016 Category: Neurology Authors: Reeves TM, Trimmer PA, Colley BS, Phillips LL Tags: Exp Neurol Source Type: research

Laquinimod decreases Bax expression and reduces caspase-6 activation in neurons.
Abstract Laquinimod is an immunomodulatory compound that has shown neuroprotective benefits in clinical trials for multiple sclerosis. Laquinimod ameliorates both white and gray matter damage in human patients, and prevents axonal degeneration in animal models of multiple sclerosis. Axonal damage and white matter loss are a common feature shared between different neurodegenerative diseases. Caspase-6 activation plays an important role in axonal degeneration on the molecular level. Increased activity of caspase-6 has been demonstrated in brain tissue from presymptomatic Huntington disease mutation carriers, and it ...
Source: Experimental Neurology - June 10, 2016 Category: Neurology Authors: Ehrnhoefer DE, Caron NS, Deng Y, Qiu X, Tsang M, Hayden MR Tags: Exp Neurol Source Type: research

Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth.
Pasquini JM Abstract Axonal growth cone collapse following spinal cord injury (SCI) is promoted by semaphorin3A (Sema3A) signaling via PlexinA4 surface receptor. This interaction triggers intracellular signaling events leading to increased hydrogen peroxide levels which in turn promote filamentous actin (F-actin) destabilization and, subsequent inhibition of axonal re-growth. In the current study, we demonstrated that treatment with galectin-1 (Gal-1), in its dimeric form, promotes a decrease in hydrogen peroxide (H2O2) levels and F-actin repolimerization in the growth cone and in the filopodium of neuron surfaces...
Source: Experimental Neurology - June 10, 2016 Category: Neurology Authors: Quintá HR, Wilson C, Blidner AG, González-Billault C, Pasquini LA, Rabinovich GA, Pasquini JM Tags: Exp Neurol Source Type: research

The history of myelin.
Abstract Andreas Vesalius can be attributed the discovery of white matter in the 16th century but Van Leeuwenhoek is arguably the first to have observed myelinated fibers in 1717. A globular myelin theory followed claiming all elements of the nervous system, except for Fontana primitive cylinder with outer sheath in 1781. Remak axon revolution in 1836 relegated myelin to the unknown. Ehrenberg described nerve tubes with double borders in 1833, and Schwann nuclei in 1839, but the medullary sheath acquired its name of myelin coined by Virchow only in 1854. Thanks to Schultze osmium specific staining in 1865, myelin ...
Source: Experimental Neurology - June 8, 2016 Category: Neurology Authors: Boullerne AI Tags: Exp Neurol Source Type: research

Experience-dependent reduction of soluble β-amyloid oligomers and rescue of cognitive abilities in middle-age Ts65Dn mice, a model of Down syndrome.
Experience-dependent reduction of soluble β-amyloid oligomers and rescue of cognitive abilities in middle-age Ts65Dn mice, a model of Down syndrome. Exp Neurol. 2016 Jun 7;283(Pt A):49-56 Authors: Sansevero G, Begenisic T, Mainardi M, Sale A Abstract Down syndrome (DS) is the most diffused genetic cause of intellectual disability and, after the age of forty, is invariantly associated with Alzheimer's disease (AD). In the last years, the prolongation of life expectancy in people with DS renders the need for intervention paradigms aimed at improving mental disability and counteracting AD pathology ...
Source: Experimental Neurology - June 7, 2016 Category: Neurology Authors: Sansevero G, Begenisic T, Mainardi M, Sale A Tags: Exp Neurol Source Type: research

Influence of Early Life Status Epilepticus on the Developmental Expression Profile of the GluA2 Subunit of AMPA Receptors.
eš P Abstract AMPA receptors (AMPARs) are responsible for fast excitatory neurotransmission, and their prolonged activation can result in the generation and spread of epileptic seizures. At early stages of postnatal development, the majority of AMPARs are permeable to both Na(+) and Ca(2+) ions. This permeability, which increases neuronal excitability, is due to the lack of the GluA2 subunit, encoded by the GRIA2A gene, and/or the presence of an unedited GluA2 subunit Q/R site (glutamine instead of arginine). Lithium chloride- and pilocarpine-induced status epilepticus (LiCl/Pilo-SE) in rodents represents a...
Source: Experimental Neurology - June 7, 2016 Category: Neurology Authors: Szczurowska E, Ergang P, Kubová H, Druga R, Salaj M, Mareš P Tags: Exp Neurol Source Type: research

The tyrosine kinase inhibitor, sunitinib malate, induces cognitive impairment in vivo via dysregulating VEGFR signaling, apoptotic and autophagic machineries.
Abstract Chemobrain refers to a cluster of cognitive deficits which affects almost 4-75% of chemotherapy-treated cancer patients. Sunitinib, FDA-approved multityrosine kinase inhibitor, is currently used in treating different types of tumors. Despite being regarded as targeted therapy which blunts sustained angiogenesis in cancer milieu through inhibiting vascular endothelial growth factor receptor 2 (VEGFR2) signaling, the latter has cardinal role in cognition. Recent clinical reports warned that sunitinib adversely affected memory processing in cancer patients. Nevertheless, the underlying mechanisms have not be...
Source: Experimental Neurology - June 7, 2016 Category: Neurology Authors: Abdel-Aziz AK, Mantawy EM, Said RS, Helwa R Tags: Exp Neurol Source Type: research

Predator-based psychosocial stress animal model of PTSD: Preclinical assessment of traumatic stress at cognitive, hormonal, pharmacological, cardiovascular and epigenetic levels of analysis.
Abstract Research on post-traumatic stress disorder (PTSD) is faced with the challenge of understanding how a traumatic experience produces long-lasting detrimental effects on behavior and brain functioning, and more globally, how stress exacerbates somatic disorders, including cardiovascular disease. Moreover, the design of translational research needs to link animal models of PTSD to clinically relevant risk factors which address why only a subset of traumatized individuals develop persistent psychopathology. In this review, we have summarized our psychosocial stress rodent model of PTSD which is based on well-d...
Source: Experimental Neurology - June 6, 2016 Category: Neurology Authors: Zoladz PR, Diamond DM Tags: Exp Neurol Source Type: research

Corrigendum to "Combination therapy with lenalidomide and nanoceria ameliorates CNS autoimmunity", [Exp. Neurol. 273 (2015), 151-160].
Corrigendum to "Combination therapy with lenalidomide and nanoceria ameliorates CNS autoimmunity", [Exp. Neurol. 273 (2015), 151-160]. Exp Neurol. 2016 Jun;280:121 Authors: Eitan E, Hutchison ER, Greig NH, Tweedie D, Celik H, Ghosh S, Fishbein KW, Spencer RG, Sasaki CY, Ghosh P, Das S, Chigurapati S, Raymick J, Sarkar S, Chigurupati S, Seal S, Mattson MP PMID: 27149927 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 8, 2016 Category: Neurology Authors: Eitan E, Hutchison ER, Greig NH, Tweedie D, Celik H, Ghosh S, Fishbein KW, Spencer RG, Sasaki CY, Ghosh P, Das S, Chigurapati S, Raymick J, Sarkar S, Chigurupati S, Seal S, Mattson MP Tags: Exp Neurol Source Type: research

Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy.
In this study, we investigated the expression of GLT1 and AQP4 in the intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). We used real-time polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis at 1, 4, 7, and 30days after kainic acid-induced status epilepticus (SE) to determine hippocampal glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes), GLT1, and AQP4 expression changes during the development of epilepsy (epileptogenesis). Following IHKA, all mice had SE and progressive increases in GFAP immunoreactivity and GFAP protein expression out to 30days...
Source: Experimental Neurology - May 4, 2016 Category: Neurology Authors: Hubbard JA, Szu JI, Yonan JM, Binder DK Tags: Exp Neurol Source Type: research

FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.
Abstract Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes>85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (F...
Source: Experimental Neurology - May 3, 2016 Category: Neurology Authors: Precious SV, Kelly CM, Reddington AE, Vinh NN, Stickland RC, Pekarik V, Scherf C, Jeyasingham R, Glasbey J, Holeiter M, Jones L, Taylor MV, Rosser AE Tags: Exp Neurol Source Type: research

A silver lining of neuroinflammation: Beneficial effects on myelination.
Abstract Myelin accelerates action potential conduction velocity and provides essential energy support for axons. Unfortunately, myelin and myelinating cells are often vulnerable to injury or disease, resulting in myelin damage, which in turn can lead to axon dysfunction, overt pathology and neurological impairment. Inflammation is a common component of trauma and disease in both the CNS and PNS and therefore an active inflammatory response is often considered deleterious to myelin health. While inflammation can certainly damage myelin, inflammatory processes also can positively affect oligodendrocyte lineage prog...
Source: Experimental Neurology - May 2, 2016 Category: Neurology Authors: Goldstein EZ, Church JS, Hesp ZC, Popovich PG, McTigue DM Tags: Exp Neurol Source Type: research

Corrigendum to "Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways" [Exp Neurol. 2015 Nov.; 273: 301-11].
Corrigendum to "Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways" [Exp Neurol. 2015 Nov.; 273: 301-11]. Exp Neurol. 2016 May;279:290 Authors: Zheng G, Hong S, Hayes JM, Wiley JW PMID: 27085462 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 19, 2016 Category: Neurology Authors: Zheng G, Hong S, Hayes JM, Wiley JW Tags: Exp Neurol Source Type: research

Does the preclinical evidence for functional remyelination following engraftment into the injured spinal cord support progression to clinical trials?
This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cell...
Source: Experimental Neurology - April 13, 2016 Category: Neurology Authors: Myers SA, Bankston AN, Burke DA, Ohri SS, Whittemore SR Tags: Exp Neurol Source Type: research

Identification and modification of amyloid-independent phenotypes of APOE4 mice.
CONCLUSIONS: We report new phenotypes associated with APOE4 in control human and APOE knock-in mice and their mitigation with NSAID treatment, through COX-2 inhibition and PPAR-γ activation. PMID: 27085394 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 13, 2016 Category: Neurology Authors: DiBattista AM, Dumanis SB, Newman J, Rebeck GW Tags: Exp Neurol Source Type: research

Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.
Abstract Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone ma...
Source: Experimental Neurology - April 13, 2016 Category: Neurology Authors: Linares GR, Chiu CT, Scheuing L, Leng Y, Liao HM, Maric D, Chuang DM Tags: Exp Neurol Source Type: research

Promoting peripheral myelin repair.
Abstract Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropa...
Source: Experimental Neurology - April 11, 2016 Category: Neurology Authors: Zhou Y, Notterpek L Tags: Exp Neurol Source Type: research

Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.
Cummings BJ Abstract Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically
Source: Experimental Neurology - April 11, 2016 Category: Neurology Authors: Haus DL, López-Velázquez L, Gold EM, Cunningham KM, Perez H, Anderson AJ, Cummings BJ Tags: Exp Neurol Source Type: research

Enhanced recovery of breathing capacity from combined adenosine 2A receptor inhibition and daily acute intermittent hypoxia after chronic cervical spinal injury.
Abstract Daily acute intermittent hypoxia (dAIH) improves breathing capacity after C2 spinal hemisection (C2HS) in rats. Since C2HS disrupts spinal serotonergic innervation below the injury, adenosine-dependent mechanisms underlie dAIH-induced functional recovery 2weeks post-injury. We hypothesized that dAIH-induced functional recovery converts from an adenosine-dependent to a serotonin-dependent, adenosine-constrained mechanism with chronic injury. Eight weeks post-C2HS, rats began dAIH (10, 5-min episodes, 10.5% O2; 5-min intervals; 7days) followed by AIH 3× per week (3×wAIH) for 8 additional weeks w...
Source: Experimental Neurology - April 11, 2016 Category: Neurology Authors: Navarrete-Opazo A, Dougherty BJ, Mitchell GS Tags: Exp Neurol Source Type: research

Aromatase inhibitors augment nociceptive behaviors in rats and enhance the excitability of sensory neurons.
Abstract Although aromatase inhibitors (AIs) are commonly used therapies for breast cancer, their use is limited because they produce arthralgia in a large number of patients. To determine whether AIs produce hypersensitivity in animal models of pain, we examined the effects of the AI, letrozole, on mechanical, thermal, and chemical sensitivity in rats. In ovariectomized (OVX) rats, administering a single dose of 1 or 5mg/kg letrozole significantly reduced mechanical paw withdrawal thresholds, without altering thermal sensitivity. Repeated injection of 5mg/kg letrozole in male rats produced mechanical, but not the...
Source: Experimental Neurology - April 9, 2016 Category: Neurology Authors: Robarge JD, Duarte DB, Shariati B, Wang R, Flockhart DA, Vasko MR Tags: Exp Neurol Source Type: research