Neuronal prolyl-4-hydroxylase 2 deficiency improves cognitive abilities in a murine model of cerebral hypoperfusion.
Abstract Episodes of cerebral hypoxia/ischemia increase the risk of dementia, which is associated with impaired learning and memory. Previous studies in rodent models of dementia indicated a favorable effect of the hypoxia-inducible factor (HIF) targets VEGF (vascular endothelial growth factor) and erythropoietin (Epo). In the present study we thus investigated whether activation of the entire adaptive HIF pathway in neurons by cell-specific deletion of the HIF suppressor prolyl-4-hydroxylase 2 (PHD2) improves cognitive abilities in young (3months) and old (18-28months) mice suffering from chronic brain hypoperfus...
Source: Experimental Neurology - October 5, 2016 Category: Neurology Authors: Gruneberg D, Montellano FA, Plaschke K, Li L, Marti HH, Kunze R Tags: Exp Neurol Source Type: research
Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures.
Abstract Explosives create shockwaves that cause blast-induced neurotrauma, one of the most common types of traumatic brain injury (TBI) linked to military service. Blast-induced TBIs are often associated with reduced cognitive and behavioral functions due to a variety of factors. To study the direct effects of military explosive blasts on brain tissue, we removed systemic factors by utilizing rat hippocampal slice cultures. The long-term slice cultures were briefly sealed air-tight in serum-free medium, lowered into a 37°C water-filled tank, and small 1.7-gram assemblies of cyclotrimethylene trinitramine (RDX...
Source: Experimental Neurology - October 5, 2016 Category: Neurology Authors: Smith M, Piehler T, Benjamin R, Farizatto KL, Pait MC, Almeida MF, Ghukasyan VV, Bahr BA Tags: Exp Neurol Source Type: research
Special Issue: New Perspectives in PTSD.
PMID: 27719965 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - October 1, 2016 Category: Neurology Authors: Wilson MA, Reagan LP Tags: Exp Neurol Source Type: research
Impairment of decision making associated with disruption of phase-locking in the anterior cingulate cortex in viscerally hypersensitive rats.
Abstract Visceral hypersensitivity (VH) is a key factor of irritable bowel syndrome (IBS). Previous studies have identified an enhanced response of anterior cingulate cortex (ACC) to colorectal distension in VH rats, which can be observed up to 7weeks following colonic anaphylaxis, independent of colonic inflammation. The induction of VH produces a change in the ability to induce subsequent synaptic plasticity at the ACC circuitry. In clinical practice, a positive link between IBS and cognitive impairments has been noted for years, but no animal model has been reported. Decision-making is a valuable model for moni...
Source: Experimental Neurology - September 21, 2016 Category: Neurology Authors: Cao B, Wang J, Mu L, Poon DC, Li Y Tags: Exp Neurol Source Type: research
Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.
Abstract Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show ...
Source: Experimental Neurology - September 19, 2016 Category: Neurology Authors: Bordia T, Zhang D, Perez XA, Quik M Tags: Exp Neurol Source Type: research
Progressive gene dose-dependent disruption of the methamphetamine-sensitive circadian oscillator-driven rhythms in a knock-in mouse model of Huntington's disease.
Abstract Huntington's disease (HD) is a progressive genetic neurodegenerative disorder characterised by motor and cognitive deficits, as well as sleep and circadian abnormalities. In the R6/2 mouse, a fragment model of HD, rest-activity rhythms controlled by the suprachiasmatic nucleus disintegrate completely by 4months of age. Rhythms driven by a second circadian oscillator, the methamphetamine-sensitive circadian oscillator (MASCO), are disrupted even earlier, and cannot be induced after 2months of age. Here, we studied the effect of the HD mutation on the expression of MASCO-driven rhythms in a more slowly deve...
Source: Experimental Neurology - September 16, 2016 Category: Neurology Authors: Ouk K, Aungier J, Morton AJ Tags: Exp Neurol Source Type: research
A new model of nerve injury in the rat reveals a role of regulator of G protein signaling 4 in tactile hypersensitivity.
In this study we have modified the rat model of spared nerve injury, restricting the surgical lesion to a single peripheral branch of the sciatic nerve. This modification reduced the prevalence of tactile hypersensitivity from nearly 100% to approximately 50%. With this model, we here also demonstrated that the Regulator of G protein Signaling 4 (RGS4) was specifically up-regulated in the lumbar dorsal root ganglia and dorsal horn of rats developing tactile hypersensitivity. Intrathecal delivery of the RGS4 inhibitor CCG63802 was found to reverse tactile hypersensitivity for a 1h period. Moreover, tactile hypersensitivity ...
Source: Experimental Neurology - September 15, 2016 Category: Neurology Authors: Taccola G, Doyen PJ, Damblon J, Dingu N, Ballarin B, Steyaert A, Rieux AD, Forget P, Hermans E, Bosier B, Deumens R Tags: Exp Neurol Source Type: research
Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.
Abstract Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical s...
Source: Experimental Neurology - September 14, 2016 Category: Neurology Authors: Huang YJ, Lee KH, Murphy L, Garraway SM, Grau JW Tags: Exp Neurol Source Type: research
Activation of LILRB2 signal pathway in temporal lobe epilepsy patients and in a pilocarpine induced epilepsy model.
Abstract Temporal lobe epilepsy (TLE) is a frequent form of focal intractable epilepsy in adults, but the specific mechanism underlying the epileptogenesis of TLE is still unknown. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) (the murine homolog gene called paired immunoglobulin-like receptor B, or PirB), participates in the process of synaptic plasticity and neurite growth in the central nervous system (CNS), suggesting a potential role of LILRB2 in epilepsy. However, the expression pattern of LILRB2 and the downstream molecular signal in intractable TLE remains poorly understood. In the present study...
Source: Experimental Neurology - September 13, 2016 Category: Neurology Authors: Yue J, Li W, Liang C, Chen B, Chen X, Wang L, Zang Z, Yu S, Liu S, Li S, Yang H Tags: Exp Neurol Source Type: research
Chronic mild stress accelerates the progression of Parkinson's disease in A53T α-synuclein transgenic mice.
Chronic mild stress accelerates the progression of Parkinson's disease in A53T α-synuclein transgenic mice. Exp Neurol. 2016 Sep 13; Authors: Wu Q, Yang X, Zhang Y, Zhang L, Feng L Abstract Daily stress is associated with increased risk for various diseases, and numerous studies have provided evidence that environmental stress leads to deleterious effects on the central nervous system. However, it remains unclear whether chronic stress exacerbates the progression of Parkinson's disease (PD). To investigate this hypothesis, we determined the effect of chronic mild stress (CMS) on the pathogenesis...
Source: Experimental Neurology - September 13, 2016 Category: Neurology Authors: Wu Q, Yang X, Zhang Y, Zhang L, Feng L Tags: Exp Neurol Source Type: research
α-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function.
This study therefore shows for the first time that misfolded α-synuclein can interact and affect the cerebral endothelial system, although its relevance to the pathogenesis of Parkinson's disease remains to be elucidated. PMID: 27632900 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 12, 2016 Category: Neurology Authors: Kuan WL, Bennett N, He X, Skepper JN, Martynyuk N, Wijeyekoon R, Moghe PV, Williams-Gray CH, Barker RA Tags: Exp Neurol Source Type: research
MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain.
In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8(+) T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the sp...
Source: Experimental Neurology - September 9, 2016 Category: Neurology Authors: Fu Q, Shi D, Zhou Y, Zheng H, Xiang H, Tian X, Gao F, Manyande A, Cao F, Tian Y, Ye D Tags: Exp Neurol Source Type: research
Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral nociception and hypersensitivity.
In conclusion, TRPM2 channels contribute to visceral nociception in response to noxious stimuli under normal conditions and visceral hypersensitivity in pathological conditions. PMID: 27616276 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 8, 2016 Category: Neurology Authors: Matsumoto K, Takagi K, Kato A, Ishibashi T, Mori Y, Tashima K, Mitsumoto A, Kato S, Horie S Tags: Exp Neurol Source Type: research
Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat.
Abstract Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4-8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate ex...
Source: Experimental Neurology - September 1, 2016 Category: Neurology Authors: Gordon T, de Zepetnek JE Tags: Exp Neurol Source Type: research
Special Issue: Myelin Repair.
PMID: 27590981 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 1, 2016 Category: Neurology Authors: McTigue D Tags: Exp Neurol Source Type: research
Expression of brain-derived neurotrophic factor in astrocytes - Beneficial effects of glatiramer acetate in the R6/2 and YAC128 mouse models of Huntington's disease.
In this study, we investigate effects of GA on BDNF expression especially in astrocytes in vitro and in vivo in brains of R6/2 and YAC128 transgenic mouse models of Huntington's disease (HD) where a pathogenic role of astroglial cells has recently been shown. We show that GA increases the expression of functionally active BDNF in astrocyte culture and in astrocytes of GA treated HD mice. In the brains of these mice, GA decreases neurodegeneration and restores BDNF levels. The beneficial effect of GA in R6/2 mice also comprises reduced weight loss and prolonged life span and, for both models, also improved motor performance...
Source: Experimental Neurology - August 29, 2016 Category: Neurology Authors: Reick C, Ellrichmann G, Tsai T, Lee DH, Wiese S, Gold R, Saft C, Linker RA Tags: Exp Neurol Source Type: research
Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury.
Abstract Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeut...
Source: Experimental Neurology - August 28, 2016 Category: Neurology Authors: Hormigo KM, Zholudeva LV, Spruance VM, Marchenko V, Cote MP, Vinit S, Giszter S, Bezdudnaya T, Lane MA Tags: Exp Neurol Source Type: research
Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxia.
Abstract Perinatal asphyxia (PA) is one of the most frequent risk factors for several neurodevelopmental disorders (NDDs) of presumed multifactorial etiology. Dysfunction of neuronal connectivity is thought to play a central role in the pathophysiology of NDDs. Because underlying causes of some NDDs begin before/during birth, we asked whether this clinical condition might affect accurate establishment of neural circuits in the hippocampus as a consequence of disturbed brain plasticity. We used a murine model that mimics the pathophysiological processes of perinatal asphyxia. Histological analyses of neurons (NeuN)...
Source: Experimental Neurology - August 27, 2016 Category: Neurology Authors: Saraceno GE, Caceres LG, Guelman L, Castilla R, Udovin LD, Ellisman MH, Brocco MA, Capani F Tags: Exp Neurol Source Type: research
Corrigendum to "Loss of Ca2+-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain" [Experimental Neurology 279 (2016) 168-177].
Corrigendum to "Loss of Ca2+-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain" [Experimental Neurology 279 (2016) 168-177]. Exp Neurol. 2016 Aug 26; Authors: Chen Y, Derkach VA, Smith PA PMID: 27574732 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 26, 2016 Category: Neurology Authors: Chen Y, Derkach VA, Smith PA Tags: Exp Neurol Source Type: research
Acute hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the C1 region.
Abstract Catecholaminergic C1 cells reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM) and can be activated by hypoxia. These neurons regulate the hypothalamic pituitary axis via direct projections to the hypothalamic paraventricular nucleus (PVH) and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. Based on the various effects attributed to the C1 cells and what is currently known of their synaptic inputs, our hypothesis is that acute hypoxia (AH) activates RVLM projecting catecholaminergic neurons to PVH. Anterograde ...
Source: Experimental Neurology - August 25, 2016 Category: Neurology Authors: Silva TM, Takakura AC, Moreira TS Tags: Exp Neurol Source Type: research
Axon regeneration in C. elegans: Worming our way to mechanisms of axon regeneration.
Abstract How axons repair themselves after injury is a fundamental question in neurobiology. With its conserved genome, relatively simple nervous system, and transparent body, C. elegans has recently emerged as a productive model to uncover the cellular mechanisms that regulate and execute axon regeneration. In this review, we discuss the strengths and weaknesses of the C. elegans model of regeneration. We explore the technical advances that enable the use of C. elegans for in vivo regeneration studies, review findings in C. elegans that have contributed to our understanding of the regeneration response across spe...
Source: Experimental Neurology - August 25, 2016 Category: Neurology Authors: Byrne AB, Hammarlund M Tags: Exp Neurol Source Type: research
Preservation of neuromuscular function in symptomatic SOD1-G93A mice by peripheral infusion of methylene blue.
This study tested whether localized peripheral application of a protective drug could effectively preserve neuromuscular junctions in late-stage disease. Methylene blue (MB), which has mitochondria-protective properties, was infused via an osmotic pump into the anterior muscle compartment of one hind limb of late pre- symptomatic SOD1-G93A mice for ≥3weeks. When mice reached end-stage disease, peak twitch and tetanic contractions evoked by stimulation of the muscle nerve were measured in two anterior compartment muscles (tibialis anterior [TA] and extensor digitorum longus [EDL], both predominantly fast muscles). With 4...
Source: Experimental Neurology - August 24, 2016 Category: Neurology Authors: Talbot JD, Barrett JN, Nonner D, Zhang Z, Wicomb K, Barrett EF Tags: Exp Neurol Source Type: research
HSPB3 protein is expressed in motoneurons and induces their survival after lesion-induced degeneration.
Abstract The human small heat shock proteins (HSPBs) form a family of molecular chaperones comprising ten members (HSPB1-HSPB10), whose functions span from protein quality control to cytoskeletal dynamics and cell death control. Mutations in HSPBs can lead to human disease and particularly point mutations in HSPB1 and HSPB8 are known to lead to peripheral neuropathies. Recently, a missense mutation (R7S) in yet another member of this family, HSPB3, was found to cause an axonal motor neuropathy (distal hereditary motor neuropathy type 2C, dHMN2C). Until now, HSPB3 protein localization and function in motoneurons (M...
Source: Experimental Neurology - August 24, 2016 Category: Neurology Authors: La Padula V, Staszewski O, Nestel S, Busch H, Boerries M, Roussa E, Prinz M, Krieglstein K Tags: Exp Neurol Source Type: research
Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula.
Abstract The interrelation of depression and pain is increasingly coming under scrutiny. Although the lateral habenula (LHb) is widely implicated in the pathogenesis of depression and pain, its role in the interaction of depression and pain remains unknown. Thus, the aim of current study was to investigate the role of LHb in rat depression-pain comorbidity. Single extracellular firing recording and immunofluorescence methods were used to compare firing rates and c-Fos expression of the LHb neurons in normal and model rats. Following subcutaneous injection of formalin into the hind paw to simulate natural pain, we ...
Source: Experimental Neurology - August 20, 2016 Category: Neurology Authors: Li J, Li Y, Zhang B, Shen X, Zhao H Tags: Exp Neurol Source Type: research
Gastrin-releasing peptide facilitates glutamatergic transmission in hippocampus and effectively prevents vascular dementia induced cognitive and synaptic plasticity deficits.
In this study, we first investigated the effects of GRP on glutamatergic transmission with patch-clamp recording. We found that acute application of GRP enhanced the excitatory synaptic transmission in hippocampal CA1 neurons via GRPR in a presynaptic mechanism. Secondly, we examined whether exogenous GRP or its analogue neuromedin B (NMB) could prevent VD-induced cognitive deficits and the mechanism of synaptic plasticity. By using Morris water maze, long-term potentiation (LTP) recording, western blot assay and immunofluorescent staining, we verified for the first time that GRP or NMB substantially improved the spatial l...
Source: Experimental Neurology - August 15, 2016 Category: Neurology Authors: Yang J, Yao Y, Wang L, Yang C, Wang F, Guo J, Wang Z, Yang Z, Ming D Tags: Exp Neurol Source Type: research
Harnessing the power of cell transplantation to target respiratory dysfunction following spinal cord injury.
Abstract The therapeutic benefit of cell transplantation has been assessed in a host of central nervous system (CNS) diseases, including disorders of the spinal cord such as traumatic spinal cord injury (SCI). The promise of cell transplantation to preserve and/or restore normal function can be aimed at a variety of therapeutic mechanisms, including replacement of lost or damaged CNS cell types, promotion of axonal regeneration or sprouting, neuroprotection, immune response modulation, and delivery of gene products such as neurotrophic factors, amongst other possibilities. Despite significant work in the field of ...
Source: Experimental Neurology - August 13, 2016 Category: Neurology Authors: Charsar BA, Urban MW, Lepore AC Tags: Exp Neurol Source Type: research
Regulation of brain PPARgamma2 contributes to ketogenic diet anti-seizure efficacy.
Abstract The ketogenic diet (KD) is an effective therapy primarily used in pediatric patients whom are refractory to current anti-seizure medications. The mechanism of the KD is not completely understood, but is thought to involve anti-inflammatory and anti-oxidant processes. The nutritionally-regulated transcription factor peroxisome proliferator activated receptor gamma, PPARγ, regulates genes involved in anti-inflammatory and anti-oxidant pathways. Moreover, endogenous ligands of PPARγ include fatty acids suggesting a potential role in the effects of the KD. Here, we tested the hypothesis that PPAR&...
Source: Experimental Neurology - August 12, 2016 Category: Neurology Authors: Simeone TA, Matthews SA, Samson KK, Simeone KA Tags: Exp Neurol Source Type: research
NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats.
Abstract Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na(+)] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in...
Source: Experimental Neurology - August 12, 2016 Category: Neurology Authors: Izumida H, Takagi H, Fujisawa H, Iwata N, Nakashima K, Takeuchi S, Iwama S, Namba T, Komatu Y, Kaibuchi K, Oiso Y, Arima H, Sugimura Y Tags: Exp Neurol Source Type: research
Neuroprosthetics in amputee and brain injury rehabilitation.
Abstract The goals of rehabilitation medicine programs are to promote health, restore functional impairments and improve quality of life. The field of neuroprosthetics has evolved over the last decade given an improved understanding of neuroscience and the incorporation of advanced biotechnology and neuroengineering in the rehabilitation setting to develop adaptable applications to help facilitate recovery for individuals with amputations and brain injury. These applications may include a simple cognitive prosthetics aid for impaired memory in brain-injured individuals to myoelectric prosthetics arms with artifici...
Source: Experimental Neurology - August 9, 2016 Category: Neurology Authors: Eapen BC, Murphy DP, Cifu DX Tags: Exp Neurol Source Type: research
The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces.
Abstract A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces. Despite these s...
Source: Experimental Neurology - August 7, 2016 Category: Neurology Authors: O'Shea DJ, Trautmann E, Chandrasekaran C, Stavisky S, Kao J, Sahani M, Ryu S, Deisseroth K, Shenoy KV Tags: Exp Neurol Source Type: research
Odor-induced recall of emotional memories in PTSD-review and new paradigm for research.
Abstract It is clinically well known that olfactory intrusions in PTSD can be a disabling phenomena due to the involuntary recall of odor memories. Odorants can trigger involuntary recall of emotional memories as well have the potential to help diminishing emotional arousal as grounding stimuli. Despite major advances in our understanding of the function of olfactory system, the study of the relation of olfaction and emotional memory is still relatively scarce. Odor memory is long thought to be different than other types of memories such as verbal or visual memories, being more strongly engraved and more closely r...
Source: Experimental Neurology - August 7, 2016 Category: Neurology Authors: Daniels JK, Vermetten E Tags: Exp Neurol Source Type: research
Mitochondrial STAT3 is negatively regulated by SOCS3 and upregulated after spinal cord injury.
Abstract Suppressor of cytokine signaling-3 (SOCS3) expression is induced by the Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling pathway. SOCS3 then acts as a feedback inhibitor of JAK-STAT signaling. Previous studies have shown that knocking down SOCS3 in spinal cord neurons with Lentiviral delivery of SOCS3-targeting shRNA (shSOCS3) increased spinal cord injury (SCI)-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr), which in part contributed to decreased neuronal death and demyelination as well as enhanced dendritic regeneration and protection of neuronal morphology...
Source: Experimental Neurology - August 5, 2016 Category: Neurology Authors: Park KW, Lin CY, Benveniste EN, Lee YS Tags: Exp Neurol Source Type: research
Activation of CRHR1 receptors regulates social and depressive-like behaviors and expression of BDNF and TrkB in mesocorticolimbic regions following global cerebral ischemia.
Abstract Increased HPA axis activation and CRH release characterize the brain's response to global cerebral ischemia. Recently, CRH via activation of CRH type 1 receptors (CRHR1) has been shown to regulate Brain Derived Neurotrophic Factor (BDNF) secretion and emotional behavior. The current study investigates the impact of CRHR1 blockade on BDNF/TrkB signaling expression in the mesolimbic circuitry, and social and depressive-like behavior following global ischemia. Adult male Wistar rats were injected with Antalarmin (2μg/μl) or a vehicle 30min prior to 10min global cerebral ischemia (4VO model) or sham occ...
Source: Experimental Neurology - August 3, 2016 Category: Neurology Authors: de la Tremblaye PB, Linares NN, Schock S, Plamondon H Tags: Exp Neurol Source Type: research
Treating refractory mental illness with closed-loop brain stimulation: Progress towards a patient-specific transdiagnostic approach.
We present convergent preliminary evidence from functional neuroimaging, invasive human electrophysiology, and human brain stimulation experiments suggesting that this approach is feasible. Using the Emotional Conflict Resolution (ECR) task as an example, we show that emotion-related networks can be identified and modulated in individual patients. Invasive and non-invasive methodologies both identify a network between prefrontal cortex, cingulate cortex, insula, and amygdala. Further, stimulation in cingulate and amygdala changes patients' performance in ways that are linked to the task's emotional content. We present prel...
Source: Experimental Neurology - July 30, 2016 Category: Neurology Authors: Widge AS, Ellard KK, Paulk AC, Basu I, Yousefi A, Zorowitz S, Gilmour A, Afzal A, Deckersbach T, Cash SS, Kramer MA, Eden UT, Dougherty DD, Eskandar EN Tags: Exp Neurol Source Type: research
New translational perspectives for blood-based biomarkers of PTSD: From glucocorticoid to immune mediators of stress susceptibility.
Abstract Although biological systems have evolved to promote stress-resilience, there is variation in stress-responses. Understanding the biological basis of such individual differences has implications for understanding Posttraumatic Stress Disorder (PTSD) etiology, which is a maladaptive response to trauma occurring only in a subset of vulnerable individuals. PTSD involves failure to reinstate physiological homeostasis after traumatic events and is due to either intrinsic or trauma-related alterations in physiological systems across the body. Master homeostatic regulators that circulate and operate throughout th...
Source: Experimental Neurology - July 29, 2016 Category: Neurology Authors: Daskalakis NP, Cohen H, Nievergelt CM, Baker DG, Buxbaum JD, Russo SJ, Yehuda R Tags: Exp Neurol Source Type: research
Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons.
Abstract Developmental nicotine exposure (DNE) is associated with increased risk of cardiorespiratory, intellectual, and behavioral abnormalities in neonates, and is a risk factor for apnea of prematurity, altered arousal responses and Sudden Infant Death Syndrome. Alterations in nicotinic acetylcholine receptor signaling (nAChRs) after DNE lead to changes in excitatory neurotransmission in neural networks that control breathing, including a heightened excitatory response to AMPA microinjection into the hypoglossal motor nucleus. Here, we report on experiments designed to probe possible postsynaptic and presynapti...
Source: Experimental Neurology - July 29, 2016 Category: Neurology Authors: Cholanian M, Powell GL, Levine RB, Fregosi RF Tags: Exp Neurol Source Type: research
The impact of inflammation on respiratory plasticity.
Abstract Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosenso...
Source: Experimental Neurology - July 27, 2016 Category: Neurology Authors: Hocker AD, Stokes JA, Powell FL, Huxtable AG Tags: Exp Neurol Source Type: research
Reduced respiratory neural activity elicits a long-lasting decrease in the CO2 threshold for apnea in anesthetized rats.
Abstract Two critical parameters that influence breathing stability are the levels of arterial pCO2 at which breathing ceases and subsequently resumes - termed the apneic and recruitment thresholds (AT and RT, respectively). Reduced respiratory neural activity elicits a chemoreflex-independent, long-lasting increase in phrenic burst amplitude, a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF). The physiological significance of iPMF is unknown. To determine if iPMF and neural apnea have long-lasting physiological effects on breathing, we tested the hypothesis that patterns of neural...
Source: Experimental Neurology - July 26, 2016 Category: Neurology Authors: Baertsch NA, Baker TL Tags: Exp Neurol Source Type: research
Deficiency in matrix metalloproteinase-2 results in long-term vascular instability and regression in the injured mouse spinal cord.
Abstract Angiogenesis plays a critical role in wound healing after spinal cord injury.Therefore, understanding the events that regulate angiogenesis has considerable relevance from a therapeutic standpoint.We evaluated the contribution of matrix metalloproteinase (MMP)-2 to angiogenesis and vascular stability in spinal cord injured MMP-2 knockout and wildtype (WT) littermates.While MMP-2 deficiency resulted in reduced endothelial cell division within the lesioned epicenter, there were no genotypic differences in vascularity (vascular density, vascular area, and endothelial cell number) over the first two weeks pos...
Source: Experimental Neurology - July 25, 2016 Category: Neurology Authors: Trivedi A, Zhang H, Ekeledo A, Lee S, Werb Z, Plant GW, Noble-Haeusslein LJ Tags: Exp Neurol Source Type: research
Toward an Operational Neuroethical Risk Analysis and Mitigation Paradigm for Emerging Neuroscience and Technology (NeuroS/T).
Abstract Research in neuroscience and neurotechnology (neuroS/T) is progressing at a rapid pace with translational applications both in medicine, and more widely in the social milieu. Current and projected neuroS/T research and its applications evoke a number of neuroethicolegal and social issues (NELSI). This paper defines inherent and derivative NELSI of current and near-term neuroS/T development and engagement, and provides an overview of our group's ongoing work to develop a systematized approach to their address. Our proposed operational neuroethical risk assessment and mitigation paradigm (ONRAMP) is present...
Source: Experimental Neurology - July 25, 2016 Category: Neurology Authors: Giordano J Tags: Exp Neurol Source Type: research
A decrease of ripples precedes seizure onset in mesial temporal lobe epilepsy.
Abstract High-frequency oscillations (HFOs) are promising biomarkers for epileptic foci; however, their characteristic changes during the preictal period remain unclear. Here, the preictal HFOs were recorded and detected by an automated HFOs detection method in the mouse pilocarpine model as well as in patients with mesial temporal lobe epilepsy (mTLE) and neocortical epilepsy. A total of sixteen low-voltage fast (LVF) and fifty-three hypersynchronous-onset (HYP) seizures were recorded in ten mice. The rate of ripples (80-250Hz) decreased during 1min before the onset of LVF and HYP seizures, which was primarily du...
Source: Experimental Neurology - July 22, 2016 Category: Neurology Authors: Xu C, Wang S, Wang Y, Lin K, Pan G, Xu Z, Gonzalez-Martinez J, Gao F, Wu X, Zhang S, Bulacio JC, Najm IM, Luo J, Hu W, Wu Z, So NK, Chen Z Tags: Exp Neurol Source Type: research
Accessory respiratory muscles enhance ventilation in ALS model mice and are activated by excitatory V2a neurons.
Abstract Inspiratory accessory respiratory muscles (ARMs) enhance ventilation when demands are high, such as during exercise and/or pathological conditions. Despite progressive degeneration of phrenic motor neurons innervating the diaphragm, amyotrophic lateral sclerosis (ALS) patients and rodent models are able to maintain ventilation at early stages of disease. In order to assess the contribution of ARMs to respiratory compensation in ALS, we examined the activity of ARMs and ventilation throughout disease progression in SOD1(G93A) ALS model mice at rest using a combination of electromyography and unrestrained w...
Source: Experimental Neurology - July 22, 2016 Category: Neurology Authors: Romer SH, Seedle K, Turner SM, Li J, Baccei ML, Crone SA Tags: Exp Neurol Source Type: research
Transient loss of consciousness during hypercapnia and hypoxia: Involvement of pathways associated with general anesthesia.
Abstract Transient loss of consciousness (TLOC), frequently triggered by perturbation in essential physiological parameters such as pCO2or O2, is considered a passive consequence of generalized degradation in high-level cerebral functioning.However, the fact that it is almost always accompanied by atonia and loss of spinal nocifensive reflexes suggests that it might actually be part of a "syndrome" mediated by neural circuitry, and ultimately be adaptive. Widespread suppression by molecules distributed in the vasculature is also the classical explanation of general anesthesia. Recent data, however, sugge...
Source: Experimental Neurology - July 22, 2016 Category: Neurology Authors: Meiri G, Lanir S, Minert A, Devor M Tags: Exp Neurol Source Type: research
Plasticity in respiratory motor neurons in response to reduced synaptic inputs: A form of homeostatic plasticity in respiratory control?
We present new analyses demonstrating that reductions in synaptic inputs to phrenic motor neurons elicit a compensatory enhancement of phrenic inspiratory motor output, a form of plasticity termed inactivity-induced phrenic motor facilitation (iPMF), that is proportional to the magnitude of activity deprivation. Although the physiological role of iPMF is not understood, we hypothesize that it may have an important role in protecting the drive to breathe during conditions of prolonged or intermittent reductions in respiratory neural activity, such as following spinal cord injury or during central sleep apnea. PMID: 274...
Source: Experimental Neurology - July 22, 2016 Category: Neurology Authors: Braegelmann KM, Streeter KA, Fields DP, Baker TL Tags: Exp Neurol Source Type: research
Neuroprosthetics and the science of patient input.
Abstract Safe and effective neuroprosthetic systems are of great interest to both DARPA and CDRH, due to their innovative nature and their potential to aid severely disabled populations.By expanding technological boundaries in human-device interfaces, these devices introduce new potential benefits and risks. Therefore patient input, which is increasingly important in weighing benefits and risks, is particularly relevant for this class of devices. FDA has been a significant contributor to an ongoing stakeholder conversation about the inclusion of the patient voice, working collaboratively to create a new framework ...
Source: Experimental Neurology - July 22, 2016 Category: Neurology Authors: Benz HL, Civillico EF Tags: Exp Neurol Source Type: research
Accumulated α-synuclein affects the progression of GM2 gangliosidoses.
Accumulated α-synuclein affects the progression of GM2 gangliosidoses. Exp Neurol. 2016 Jul 21; Authors: Suzuki K, Yamaguchi A, Yamanaka S, Kanzaki S, Kawashima M, Togo T, Katsuse O, Koumitsu N, Aoki N, Iseki E, Kosaka K, Yamaguchi K, Hashimoto M, Aoki I, Hirayasu Y Abstract The accumulation of α-synuclein (ASyn) has been observed in several lysosomal storage diseases (LSDs) but it remains unclear if ASyn accumulation contributes to LSD pathology. ASyn also accumulates in the neurons of Sandhoff disease (SD) patients and SD model mice (Hexb-/- ASyn+/+ mice). SD is a lysosomal storage disor...
Source: Experimental Neurology - July 21, 2016 Category: Neurology Authors: Suzuki K, Yamaguchi A, Yamanaka S, Kanzaki S, Kawashima M, Togo T, Katsuse O, Koumitsu N, Aoki N, Iseki E, Kosaka K, Yamaguchi K, Hashimoto M, Aoki I, Hirayasu Y Tags: Exp Neurol Source Type: research
Inspiratory muscle conditioning exercise and diaphragm gene therapy in Pompe disease: Clinical evidence of respiratory plasticity.
Abstract Pompe disease is an inherited disorder due to a mutation in the gene that encodes acid α-glucosidase (GAA). Children with infantile-onset Pompe disease develop progressive hypotonic weakness and cardiopulmonary insufficiency that may eventually require mechanical ventilation (MV). Our team conducted a first in human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory neural dysfunction in infantile-onset Pompe. Subjects (aged 2-15years, full-time MV: n=5, partial/no MV: n=4) underwent a period of preoperative inspiratory muscle conditioning exercise. The change in respiratory fun...
Source: Experimental Neurology - July 21, 2016 Category: Neurology Authors: Smith BK, Martin AD, Lawson LA, Vernot V, Marcus J, Islam S, Shafi N, Corti M, Collins SW, Byrne BJ Tags: Exp Neurol Source Type: research
Impaired regeneration in aged nerves: Clearing out the old to make way for the new.
e A Abstract Although many observational studies have shown that peripheral nerve regeneration is impaired with aging, underlying cellular and molecular mechanisms have remained obscure until recently. A series of recent genetic, live imaging and heterochronic parabiosis experiments are providing new insights into the underlying mechanisms of reduced regenerative capacity with aging. These studies show that Schwann cells in the aged animal pose a primary impediment to axon regeneration in older animals as they fail to support regenerating axons, while the contribution from macrophages remains an unresolved issue. ...
Source: Experimental Neurology - July 20, 2016 Category: Neurology Authors: Scheib J, Höke A Tags: Exp Neurol Source Type: research
Activation of GABAA receptors controls mesiotemporal lobe epilepsy despite changes in chloride transporters expression: In vivo and in silico approach.
Abstract Mesiotemporal lobe Epilepsy (MTLE), the most frequent form of focal epilepsy, is often drug-resistant. Enriching the epileptic focus with GABA-releasing engineered cells has been proposed as a strategy to prevent seizures. However, ex vivo data from animal models and MTLE patients suggest that, due to changes in chloride homeostasis, GABAA receptor activation is depolarizing and partly responsible for focal interictal discharges and seizure initiation. To understand how these two contradictory aspects of GABAergic neurotransmission coexist in MTLE, we used an established mouse model of MTLE presenting hip...
Source: Experimental Neurology - July 19, 2016 Category: Neurology Authors: Stamboulian-Platel S, Legendre A, Chabrol T, Platel JC, Pernot F, Duveau V, Roucard C, Baudry M, Depaulis A Tags: Exp Neurol Source Type: research
On the prospect of clinical utilization of microRNAs as biomarkers or treatment of chronic pain - A comment on: Increased miR-132-3p expression is associated with chronic neuropathic pain.
PMID: 27438293 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - July 17, 2016 Category: Neurology Authors: Andersen HH, Johnsen KB, Arendt-Nielsen L Tags: Exp Neurol Source Type: research