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Experimental Neurology

Chiara Di Pietro, Gina La Sala, Rafaele Matteoni, Daniela Marazziti, Glauco P Tocchini-Valentini
The G-protein coupled receptor 37-like 1 (Gpr37l1) is specifically expressed in most astrocytic glial cells, including cerebellar Bergmann astrocytes and interacts with patched 1 (Ptch1), a co-receptor of the sonic hedgehog (Shh)-smoothened (Smo) signaling complex. Gpr37l1 null mutant mice exhibit precocious post-natal cerebellar development, with altered Shh-Smo mitogenic cascade and premature down-regulation of granule cell precursor (GCP) proliferation. Gpr37l1 expression is downregulated in medulloblastoma (MB) and upregulated in glioma and glioblastoma tumors...
November 16, 2018: Experimental Neurology
Cuihong Jia, Matthew P Keasey, Hannah M Malone, Chiharu Lovins, Richard R Sante, Vlad Razskazovskiy, Theo Hagg
Vitronectin (VTN) is a glycoprotein in the blood and affects hemostasis. VTN is also present in the extracellular matrix of various organs but little is known about its function in healthy adult tissues. We show, in adult mice, that VTN is uniquely expressed by approximately half of the pericytes of subventricular zone (SVZ) where neurogenesis continues throughout life. Intracerebral VTN antibody injection or VTN knockout reduced neurogenesis as well as expression of pro-neurogenic CNTF, and anti-neurogenic LIF and IL-6...
November 6, 2018: Experimental Neurology
Ryan Dobbs, Elizabeth Kalmanek, Shawn Choe, Daniel A Harrington, Samuel I Stupp, Kevin T McVary, Carol A Podlasek
INTRODUCTION: Erectile dysfunction (ED) is a significant health concern that greatly impacts quality of life, and is common in men as they age, impacting 52% of men between the ages of 40 and 70. A significant underlying cause of ED development is injury to the cavernous nerve (CN), a peripheral nerve that innervates the penis. CN injury also occurs in up to 82% of prostatectomy patients. We recently showed that Sonic hedgehog (SHH) protein delivered by peptide amphiphile (PA) nanofiber hydrogel to the CN and penis of a prostatectomy model of CN injury, is neuroprotective, accelerates CN regeneration, improves erectile function ~60%, preserves penile smooth muscle 56% and suppresses collagen deposition 30%...
November 2, 2018: Experimental Neurology
Maximilian Lenz, Christos Galanis, Dimitrios Kleidonas, Meike Fellenz, Thomas Deller, Andreas Vlachos
Neurons adjust their synaptic strength in a homeostatic manner following changes in network activity and connectivity. While this form of plasticity has been studied in detail for excitatory synapses, homeostatic plasticity of inhibitory synapses remains not well-understood. In the present study, we employed entorhinal cortex lesion (ECL) of organotypic entorhino-hippocampal tissue cultures to test for homeostatic changes in GABAergic neurotransmission onto partially denervated dentate granule cells. Using single and paired whole-cell patch-clamp recordings, as well as immunostainings for synaptic markers, we find that excitatory synaptic strength is robustly increased 3 days post lesion (dpl), whereas GABAergic neurotransmission is not changed after denervation...
October 25, 2018: Experimental Neurology
Carolina Gil-Tommee, Guadalupe Vidal-Martinez, C Annette Reyes, Javier Vargas-Medrano, Gloria V Herrera, Silver M Martin, Stephanie A Chaparro, Ruth G Perez
Parkinson's disease is a neurodegenerative disorder that reduces a patients' quality of life by the relentless progression of motor and non-motor symptoms. Among the non-motor symptoms is a condition called neurogenic bladder that is associated with detrusor muscle underactivity or overactivity occurring from neurologic damage. In Parkinson's disease, Lewy-body-like protein aggregation inside neurons typically contributes to pathology. This is associated with dopaminergic neuron loss in substantia nigra pars compacta (SNc) and in ventral tegmental area (VTA), both of which play a role in micturition...
October 25, 2018: Experimental Neurology
Andrea G Brown, Mahima Thapa, John W Hooker, Tim D Ostrowski
Besides impairment in cognition and memory, patients with Alzheimer's disease (AD) often exhibit marked dysfunction in respiratory control. Sleep-disordered breathing (SDB) is commonly found in cases of AD, resulting in periods of hypoxia during sleep. Early structural changes in brainstem areas controlling respiratory function may account for SDB in the course of AD. However, to date the underlying mechanisms for these complications are not known. The streptozotocin (STZ)-induced rat model of AD exhibits abnormal responses to hypoxia and increased astrogliosis in a key region for respiratory control...
October 23, 2018: Experimental Neurology
Yuchun Zuo, Jikai Wang, Budbazar Enkhjargal, Desislava Doycheva, Xiaoxin Yan, John H Zhang, Fei Liu
BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease that leads to poor outcomes. Neurogenesis, an essential recovery mechanism after brain injury, has not been fully elucidated after SAH. METHODS: A total of 122 SD rats were used in this study. For experiment one, the rats were randomly divided into six groups: sham and SAH with different time points (1,3,5,7,14 days) (n = 12/group). An endovascular perforation method was conducted for SAH model...
October 23, 2018: Experimental Neurology
Nicole A Hawkins, Jeffrey D Calhoun, Alexandra M Huffman, Jennifer A Kearney
Dravet syndrome is a severe, early-onset epileptic encephalopathy frequently resulting from de novo mutations of SCN1A. Mice with heterozygous deletion of Scn1a (Scn1a+/- ) model many features of Dravet syndrome, including spontaneous seizures and premature lethality. Scn1a+/- mice exhibit variable phenotype penetrance and expressivity dependent upon the strain background. On the 129S6/SvEvTac (129) strain, Scn1a+/- mice do not display an overt phenotype. However Scn1a+/- mice on the [129S6xB6]F1 strain (F1...
October 19, 2018: Experimental Neurology
Ming Chen, Da Shao, Yali Fu, Qianqian Ma, Ming Chen, Dongyang Cui, Jiaojiao Song, Huan Sheng, Li Yang, Yi Dong, Bin Lai, Ping Zheng
Addiction memory is subjected to time-dependent shifts toward neocortex in remote period to promote long-term addiction memory storage, which plays an important role in drug relapse. However, how the activity and neuroplasticity of the anterior cingulate cortex (ACC) change after contextual morphine withdrawal conditioning and what factors determine this change remain to be determined. In this paper, using immunohistochemical and single-cell microinjection techniques, combining behavioral assay, we found that (1) contextual withdrawal conditioning increases the expression of c-Fos, but not Arc, in the ACC in morphine withdrawal mice; (2) at the first day after conditioning, conditioned context has no influence on the expression of c-Fos and Arc in the ACC in morphine withdrawal mice; (3) at the 14th day after conditioning, conditioned context increases the expression of both c-Fos and Arc in the ACC in morphine withdrawal mice; (4) the inhibition of dendritic spines of the ACC or projection neurons from the CA3 of the hippocampus to the ACC attenuates the conditioned context-induced increase of Arc expression in the ACC and abolishes the retrieval of withdrawal memory at the 14th day after conditioning...
October 18, 2018: Experimental Neurology
Nathan P Cramer, Alexandru Korotcov, Asamoah Bosomtwi, Xiufen Xu, Derek R Holman, Kathleen Whiting, Scott Jones, Andrew Hoy, Bernard J Dardzinski, Zygmunt Galdzicki
We sought to understand the mechanisms underlying cognitive deficits that are reported to affect non-native subjects following their prolonged stay and/or work at high altitude (HA). We found that mice exposed to a simulated environment of 5000 m exhibit deficits in hippocampal learning and memory accompanied by abnormalities in brain MR imaging. Exposure (1-8 months) to HA led to an increase in brain ventricular volume, a reduction in relative cerebral blood flow and changes in diffusion tensor imaging (DTI) derived parameters within the hippocampus and corpus callosum...
October 13, 2018: Experimental Neurology
Ivo Eijkenboom, Maurice Sopacua, Auke B C Otten, Monique M Gerrits, Janneke G J Hoeijmakers, Stephen G Waxman, Raffaella Lombardi, Giuseppe Lauria, Ingemar S J Merkies, Hubert J M Smeets, Catharina G Faber, Jo M Vanoevelen
Small-fiber neuropathy (SFN) patients experience a spectrum of sensory abnormalities, including attenuated responses to non-noxious temperatures in combination with a decreased density of the small-nerve fibers. Gain-of-function mutations in the voltage-gated sodium channels SCN9A, SCN10A and SCN11A have been identified as an underlying genetic cause in a subpopulation of patients with SFN. Based on clinical-diagnostic tests for SFN, we have set up a panel of two read-outs reflecting SFN in zebrafish, being nerve density and behavioral responses...
October 11, 2018: Experimental Neurology
Tyler J Hanak, Jane E Libbey, Daniel J Doty, Jordan T Sim, Ana Beatriz DePaula-Silva, Robert S Fujinami
Viral encephalitis markedly increases the risk for the development of epilepsy. The Theiler's murine encephalomyelitis virus (TMEV)-induced model of seizures/epilepsy is a murine model of both viral-induced seizures/epilepsy and human Temporal Lobe Epilepsy. The inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α have been shown to play a role in seizure development in the TMEV-induced model of seizures/epilepsy, and infiltrating macrophages along with microglia have been shown to be major producers of these cytokines...
October 11, 2018: Experimental Neurology
Chong-Jin Zhong, Miao-Miao Chen, Ming Lu, Jian-Hua Ding, Ren-Hong Du, Gang Hu
ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases including stroke. Emerging evidence shows that astrocytes play important roles in the pathophysiology of cerebral ischemia. Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the exact role of astrocytic Kir6.1-containg K-ATP channel (Kir6.1/K-ATP) in ischemic stroke remains unclear. Here, we found that astrocytic Kir6...
October 10, 2018: Experimental Neurology
Anne Järve, Mihail Todiras, Xiaoming Lian, Rafael Filippelli-Silva, Fatimunnisa Qadri, Renan P Martin, Maik Gollasch, Michael Bader
Autonomic dysreflexia (AD), a syndrome caused by loss of supraspinal control over sympathetic activity and amplified vascular reflex upon sensory stimuli below injury level, is a major health problem in high-level spinal cord injury (SCI). After supraspinal sympathetic control of the vasculature below the lesion is lost, the renin-angiotensin system (RAS) is thought to be involved in AD by regulating blood pressure and vascular reactivity. In this study, we aimed to assess the role of different RAS receptors during AD following SCI...
October 10, 2018: Experimental Neurology
Jakub Trzesniewski, Sandrine Altmann, Levy Jäger, Josef P Kapfhammer
Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurodegenerative disease caused by diverse mutations in the Protein Kinase C gamma (PKCγ) gene which is one of the crucial signaling molecules of Purkinje cells. We have previously created a mouse model of SCA14 by transgenic expression of a mutated PKCγ gene causing SCA14 with a mutation in the catalytic domain. Purkinje cells from the mutated mice have a strong reduction of their dendritic tree in organotypic slice cultures typical for increased PKC activity...
October 10, 2018: Experimental Neurology
Luana da Silva Chagas, Pablo Trindade, Ana Lúcia Tavares Gomes, Henrique Rocha Mendonça, Paula Campello-Costa, Adriana da Cunha Faria Melibeu, Rafael Linden, Claudio Alberto Serfaty
Lesions in the central nervous system (CNS) can often induce structural reorganization within intact circuits of the brain. Several studies show advances in the understanding of mechanisms of brain plasticity and the role of the immune system activation. Microglia, a myeloid derived cell population colonizes the CNS during early phases of embryonic development. In the present study, we evaluated the role of microglial activation in the sprouting of intact axons following lesions of the visual pathways. We evaluated the temporal course of microglial activation in the superior colliculus following a contralateral monocular enucleation (ME) and the possible involvement of microglial cells in the plastic reorganization of the intact, uncrossed, retinotectal pathway from the remaining eye...
October 9, 2018: Experimental Neurology
Ze Zhong Wang, Shelly E Sakiyama-Elbert
Nerve injuries can be life-long debilitating traumas that severely impact patients' quality of life. While many acellular neural scaffolds have been developed to aid the process of nerve regeneration, complete functional recovery is still very difficult to achieve, especially for long-gap peripheral nerve injury and most cases of spinal cord injury. Cell-based therapies have shown many promising results for improving nerve regeneration. With recent advances in neural tissue engineering, the integration of biomaterial scaffolds and cell transplantation are emerging as a more promising approach to enhance nerve regeneration...
October 3, 2018: Experimental Neurology
Abdullah Md Sheikh, Shozo Yano, Shingo Mitaki, Md Ahsanul Haque, Shuhei Yamaguchi, Atsushi Nagai
A human mesenchymal stem cell line (B10) transplantation has been shown to improve ischemia-induced neurological deficits in animal stroke models. To understand the underlying mechanism, we have investigated the effects of B10 transplantation on cerebral angiogenesis in a rat middle cerebral artery occlusion (MCAO) model. B10 cells were transplanted intravenously 24 h after MCAO. Immunofluorescence staining results showed that compared to PBS-groups, vWF positive vessel and endoglin positive new vessels were increased in B10-transplanted MCAO groups in the lesion areas...
October 3, 2018: Experimental Neurology
Shameena Bake, Andre Okoreeh, Homa Khosravian, Farida Sohrabji
Our previous studies showed that Insulin-like Growth Factor (IGF)-1 reduced blood brain barrier permeability and decreased infarct volume caused by middle cerebral artery occlusion (MCAo) in middle aged female rats. Similarly, cultures of primary brain microvessel endothelial cells from middle-aged female rats and exposed to stroke-like conditions (oxygen glucose deprivation; OGD) confirmed that IGF-1 reduced dye transfer across this cell monolayer. Surprisingly, IGF-1 did not attenuate endothelial cell death caused by OGD...
October 1, 2018: Experimental Neurology
Alma Orts-Sebastian, Nicola M Ludin, Matthew D M Pawley, James F Cheeseman, Guy R Warman
General anaesthesia is a widely used tool to enable surgery in animal experimentation. There is now convincing evidence that general anaesthesia can cause profound and strongly time-dependant shifts in circadian rhythms of behaviour (sleep-wake cycles), physiology (core body temperature, blood pressure, heart rate and hormone release) and cognitive parameters (learning and memory) in a range of species. These effects have the potential to confound laboratory experiments, and may lead to misinterpretation of results...
September 28, 2018: Experimental Neurology
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