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Experimental Neurology

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
Luise Appeltshauser, Andreas Weishaupt, Claudia Sommer, Kathrin Doppler
Inflammatory neuropathies associated with auto-antibodies against paranodal proteins like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins (IVIG). A reason might be that IVIG interacts with the complement pathway and these auto-antibodies often belong to the IgG4 subclass that does not activate complement. However, some patients do show a response to IVIG, especially at the beginning of the disease. This corresponds with the finding of coexisting IgG subclasses IgG1, IgG2 and IgG3...
October 13, 2016: Experimental Neurology
Maximilian H Beck, Jens K Haumesser, Johanna Kühn, Jennifer Altschüler, Andrea A Kühn, Christoph van Riesen
Abnormally enhanced beta oscillations have been found in deep brain recordings from human Parkinson's disease (PD) patients and in animal models of PD. Recent correlative evidence suggests that beta oscillations are related to disease-specific symptoms such as akinesia and rigidity. However, this hypothesis has also been repeatedly questioned by studies showing no changes in beta power in animal models using an acute pharmacologic dopamine blockade. To further investigate the temporal dynamics of exaggerated beta synchrony in PD, we investigated the reserpine model, which is characterized by an acute and stable disruption of dopamine transmission, and compared it to the chronic progressive 6-hydroxydopamine (6-OHDA) model...
October 12, 2016: Experimental Neurology
Kayam Chak, Biswajoy Roy-Chaudhuri, Hak Kyun Kim, Kayla C Kemp, Brenda E Porter, Mark A Kay
MicroRNA-21 (miR-21) is consistently up-regulated in various neurological disorders, including epilepsy. Here, we show that the biogenesis of miR-21 is altered following pilocarpine status epilepticus (SE) with an increase in precursor miR-21 (pre-miR-21) in rats. We demonstrate that pre-miR-21 has an energetically favorable site overlapping with the miR-21 binding site and competes with mature miR-21 for binding in the 3'UTR of TGFBR2 mRNA, but not NT-3 mRNA in vitro. This binding competition influences miR-21-mediated repression in vitro and correlates with the increase in TGFBR2 and decrease in NT-3 following SE...
October 7, 2016: Experimental Neurology
Marquitta Smith, Thuvan Piehler, Richard Benjamin, Karen L Farizatto, Morgan C Pait, Michael F Almeida, Vladimir V Ghukasyan, Ben A Bahr
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...
October 5, 2016: Experimental Neurology
Daniel Gruneberg, Felipe A Montellano, Konstanze Plaschke, Lexiao Li, Hugo H Marti, Reiner Kunze
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 hypoperfusion...
October 5, 2016: Experimental Neurology
Giovanna Mulas, Elena Espa, Sandro Fenu, Saturnino Spiga, Giovanni Cossu, Elisabetta Pillai, Ezio Carboni, Gabriella Simbula, Dragana Jadžić, Fabrizio Angius, Stefano Spolittu, Barbara Batetta, Daniela Lecca, Andrea Giuffrida, Anna R Carta
Neuroinflammation is associated with l-DOPA treatment in Parkinson's disease (PD), suggesting a role in l-DOPA-induced dyskinesia (LID), however it is unclear whether increased inflammation is specifically related to the dyskinetic outcome of l-DOPA treatment. Diversely from oral l-DOPA, continuous intrajejunal l-DOPA infusion is associated with very low dyskinetic outcome in PD patients. We reproduced these regimens of administration in 6-OHDA-lesioned hemiparkinsonian rats, where dyskinetic responses and striatal neuroinflammation induced by chronic pulsatile (DOPAp) or continuous (DOPAc) l-DOPA were compared...
September 30, 2016: Experimental Neurology
Carlos B Mantilla
Breathing is a life-sustaining behavior that in mammals is accomplished by activation of dedicated muscles responsible for inspiratory and expiratory forces acting on the lung and chest wall. Motor control is exerted by specialized pools of motoneurons in the medulla and spinal cord innervated by projections from multiple centers primarily in the brainstem that act in concert to generate both the rhythm and pattern of ventilation. Perturbations that prevent the accomplishment of the full range of motor behaviors by respiratory muscles commonly result in significant morbidity and increased mortality...
September 30, 2016: Experimental Neurology
Hannah L Radabaugh, Lauren J Carlson, Darik A O'Neil, Megan J LaPorte, Christina M Monaco, Jeffrey P Cheng, Patricia B de la Tremblaye, Naima Lajud, Corina O Bondi, Anthony E Kline
Environmental enrichment (EE) promotes behavioral recovery after experimental traumatic brain injury (TBI). However, the chronic rehabilitation provided in the laboratory is not analogous to the clinic where physiotherapy is typically limited. Moreover, females make up approximately 40% of the clinical TBI population, yet they are seldom studied in brain trauma. Hence, the goal of this study was to test the hypothesis that abbreviated EE would confer neurobehavioral, cognitive, and histological benefits in brain injured female rats...
September 28, 2016: Experimental Neurology
Silvia Casacuberta-Serra, Carme Costa, Herena Eixarch, María José Mansilla, Sergio López-Estévez, Lluís Martorell, Marta Parés, Xavier Montalban, Carmen Espejo, Jordi Barquinero
Previous work by our group showed that transferring bone marrow cells transduced with a self-antigen induced immune tolerance and ameliorated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also found that following retroviral transduction of murine bone marrow (BM) cells, the majority of cells generated and transduced were myeloid-derived suppressor cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing MDSCs have similar therapeutic effects than those of unfractionated BM, and to investigate their potential mechanisms...
September 28, 2016: Experimental Neurology
Bing Cao, Jun Wang, Li Mu, David Chun-Hei Poon, Ying Li
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...
September 21, 2016: Experimental Neurology
Tanuja Bordia, Danhui Zhang, Xiomara A Perez, Maryka Quik
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...
September 19, 2016: Experimental Neurology
Koliane Ouk, Juliet Aungier, A Jennifer Morton
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 developing, genetically relevant mouse model of HD, the Q175 'knock-in' mouse...
September 16, 2016: Experimental Neurology
Giuliano Taccola, Pierre J Doyen, Jonathan Damblon, Nejada Dingu, Beatrice Ballarin, Arnaud Steyaert, Anne des Rieux, Patrice Forget, Emmanuel Hermans, Barbara Bosier, Ronald Deumens
Tactile hypersensitivity is one of the most debilitating symptoms of neuropathic pain syndromes. Clinical studies have suggested that its presence at early postoperative stages may predict chronic (neuropathic) pain after surgery. Currently available animal models are typically associated with consistent tactile hypersensitivity and are therefore limited to distinguish between mechanisms that underlie tactile hypersensitivity as opposed to mechanisms that protect against it. 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...
September 15, 2016: Experimental Neurology
Qiaochu Fu, Dai Shi, Yaqun Zhou, Hua Zheng, Hongbing Xiang, Xuebi Tian, Feng Gao, Anne Manyande, Fei Cao, Yuke Tian, Dawei Ye
Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8(+) T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown...
September 13, 2016: Experimental Neurology
Kristiina M Hormigo, Lyandysha V Zholudeva, Victoria M Spruance, Vitaliy Marchenko, Marie-Pascale Cote, Stephane Vinit, Simon Giszter, Tatiana Bezdudnaya, Michael A Lane
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...
August 28, 2016: Experimental Neurology
G E Saraceno, L G Caceres, L R Guelman, R Castilla, L D Udovin, M H Ellisman, M A Brocco, F Capani
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...
August 27, 2016: Experimental Neurology
Alexandra B Byrne, Marc Hammarlund
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...
August 25, 2016: Experimental Neurology
Veronica La Padula, Ori Staszewski, Sigrun Nestel, Hauke Busch, Melanie Boerries, Eleni Roussa, Marco Prinz, Kerstin Krieglstein
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)...
August 24, 2016: Experimental Neurology
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