Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway.
Abstract Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating e...
Source: Experimental Neurology - February 16, 2018 Category: Neurology Authors: Ruggiero RN, Rossignoli MT, Lopes-Aguiar C, Leite JP, Bueno-Junior LS, Romcy-Pereira RN Tags: Exp Neurol Source Type: research

Modest enhancement of sensory axon regeneration in the sciatic nerve with conditional co-deletion of PTEN and SOCS3 in the dorsal root ganglia of adult mice.
Abstract Axons within the peripheral nervous system are capable of regeneration, but full functional recovery is rare. Recent work has shown that conditional deletion of two key signaling inhibitors of the PI3K and Jak/Stat pathways-phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling-3 (SOCS3), respectively-promotes regeneration of normally non-regenerative central nervous system axons. Moreover, in studies of optic nerve regeneration, co-deletion of both PTEN and SOCS3 has an even greater effect. Here, we test the hypotheses (1) that PTEN deletion enhances axon regeneration following sciati...
Source: Experimental Neurology - February 16, 2018 Category: Neurology Authors: Gallaher ZR, Steward O Tags: Exp Neurol Source Type: research

Cell-type specific expression of constitutively-active Rheb promotes regeneration of bulbospinal respiratory axons following cervical SCI.
Abstract Damage to respiratory neural circuitry and consequent loss of diaphragm function is a major cause of morbidity and mortality in individuals suffering from traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI remains a therapeutic challenge, despite current efforts. SCI disrupts inspiratory signals originating in the rostral ventral respiratory group (rVRG) of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of...
Source: Experimental Neurology - February 14, 2018 Category: Neurology Authors: Urban MW, Ghosh B, Strojny LR, Block CG, Blazejewski SM, Wright MC, Smith GM, Lepore AC Tags: Exp Neurol Source Type: research

Amelioration of progressive autoimmune encephalomyelitis by epigenetic regulation involves selective repression of mature neutrophils during the preclinical phase.
Abstract We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced the influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II+) CD11b+Ly-6G+ neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase,...
Source: Experimental Neurology - February 14, 2018 Category: Neurology Authors: Jayaraman A, Sharma M, Prabhakar B, Holterman M, Jayaraman S Tags: Exp Neurol Source Type: research

Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.
Abstract Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if th...
Source: Experimental Neurology - February 14, 2018 Category: Neurology Authors: Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Alboghobeish S, Amirgholami N, Houshmand G, Cauli O Tags: Exp Neurol Source Type: research

Activation of liver X receptor β-enhancing neurogenesis ameliorates cognitive impairment induced by chronic cerebral hypoperfusion.
This study correlates a deficit of LXRβ in cognitive dysfunction in CCH with impaired neurogenesis in hippocampus, and LXRs may serve as a potential therapeutic target for chronic cerebral ischemia. PMID: 29447944 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 12, 2018 Category: Neurology Authors: Sun T, Li YJ, Tian QQ, Wu Q, Feng D, Xue Z, Guo YY, Yang L, Zhang K, Zhao MG, Wu YM Tags: Exp Neurol Source Type: research

Phos-tau peptide immunization of amyloid-tg-mice reduced non-mutant phos-tau pathology, improved cognition and reduced amyloid plaques.
Abstract Tau-immumotherapy has shown promising results in tangle/tauopathy-tg animal models. Here we immunized amyloid-mice (APPSwe/PSEN1dE9-tg, presenting amyloid-plaques, not neurofibrillary-tangles) with phos-tau peptides, previously shown by us to have high efficacy in mutant-tau tauopathy-mice. These amyloid-mice allowed us to test the effect of the vaccine in a model of familial AD patients with mutant amyloid plaque pathology, where tau pathology - once develops - is of non-mutant tau. Fourteen-month-old amyloid-mice were immunized with phos-tau peptides or vehicle. Eight weeks later, amelioration of cognit...
Source: Experimental Neurology - February 9, 2018 Category: Neurology Authors: Benhamron S, Rozenstein-Tsalkovich L, Nitzan K, Abramsky O, Rosenmann H Tags: Exp Neurol Source Type: research

Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.
vy OA Abstract Reduced function of parkin appears to be a central pathogenic event in Parkinson disease (PD). Increasing parkin levels enhances survival in models of PD-related neuronal death and is a promising therapeutic objective. Previously, we demonstrated that the transcription factor ATF4 promotes survival in response to PD-mimetic stressors by maintaining parkin levels. ATF4 translation is up-regulated by phosphorylation of the translation initiation factor eIF2α. The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes e...
Source: Experimental Neurology - February 9, 2018 Category: Neurology Authors: Sun X, Aimé P, Dai D, Ramalingam N, Crary JF, Burke RE, Greene LA, Levy OA Tags: Exp Neurol Source Type: research

Nigrostriatal proteasome inhibition impairs dopamine neurotransmission and motor function in minipigs.
In conclusion, direct injection of lactacystin into the MFB of minipigs provides a model of PD with reduced dopamine neurotransmission, TH-positive neuron reduction, microglial activation and behavioural deficits. This large animal model could be useful in studies of symptomatic and neuroprotective therapies with translatability to human PD. PMID: 29428213 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 8, 2018 Category: Neurology Authors: Lillethorup TP, Glud AN, Alstrup AKO, Mikkelsen TW, Nielsen EH, Zaer H, Doudet DJ, Brooks DJ, Sørensen JCH, Orlowski D, Landau AM Tags: Exp Neurol Source Type: research

The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression.
CONCLUSION: MFB DBS in the FSL animals selectively affected certain types of behaviors. Exploration and vocalization remained unaltered, but cognitive performance such as speed and precision of memory recall improved compared to unstimulated and stimulated controls. Future studies should focus on the mechanisms of action of MFB DBS, and in particular on the role of dopamine in the stimulation-dependent phenotype changes. PMID: 29428214 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 8, 2018 Category: Neurology Authors: Thiele S, Furlanetti L, Pfeiffer LM, Coenen VA, Döbrössy MD Tags: Exp Neurol Source Type: research

Spinal PKC activation - Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats.
Abstract Bone cancer pain (BCP) remains a serious complication of malignancy, which is an intractable clinical problem due to the gap in knowledge of its underlying mechanisms. Recent studies have demonstrated that the major involvement of neuroinflammation, particularly high-mobility group box 1 (HMGB1), which was identified as a late mediator of inflammation, in a number of pain conditions. However, the underlying mechanisms and functions of HMGB1 release in spinal cord, and its contributions to the development of BCP as well, are poorly understood. In the present study, we examined the theory that PKC activatio...
Source: Experimental Neurology - February 8, 2018 Category: Neurology Authors: An K, Rong H, Ni H, Zhu C, Xu L, Liu Q, Chen Y, Zheng Y, Huang B, Yao M Tags: Exp Neurol Source Type: research

Sox9 knockout mice have improved recovery following stroke.
Abstract The partial recovery that can occur after a stroke has been attributed to structural and functional plasticity that compensate for damage and lost functions. This plasticity is thought to be limited in part by the presence of growth inhibitors in the central nervous system. Blocking or reducing signals from inhibitors of axonal sprouting such as Nogo and chondroitin sulfate proteoglycans (CSPGs) increases post-stroke axonal sprouting and improves recovery. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and demonstrated that conditional Sox9 ablation leads t...
Source: Experimental Neurology - February 6, 2018 Category: Neurology Authors: Xu X, Bass B, McKillop WM, Mailloux J, Liu T, Geremia NM, Hryciw T, Brown A Tags: Exp Neurol Source Type: research

Secreted amyloid precursor protein alpha activates neuronal insulin receptors and prevents diabetes-induced encephalopathy.
In this study, in vitro analysis of cortical neuronal cultures revealed that exogenous sAPPα increased IR phosphorylation in the absence of insulin. Furthermore, in an APP overexpressing mouse model, sAPPα bound IRs in the cortex with significantly greater binding in hypoinsulinemic animals. To further examine the effects of sAPPα on the diabetic brain, we next rendered sAPPα overexpressing mice insulin depleted and found that sAPPα blocked aberrant tau phosphorylation (T231) in cortical tissue after 16 weeks diabetes. sAPPα overexpression also prevented hyperphosphorylation of AKT/GSK...
Source: Experimental Neurology - February 1, 2018 Category: Neurology Authors: Aulston BD, Shapansky J, Huang Y, Odero GL, Glazner GW Tags: Exp Neurol Source Type: research

Neuronal-specific impairment of heparan sulfate degradation in Drosophila reveals pathogenic mechanisms for Mucopolysaccharidosis type IIIA.
Abstract Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder resulting from the deficit of the N-sulfoglucosamine sulfohydrolase (SGSH) enzyme that leads to accumulation of partially-degraded heparan sulfate. MPS IIIA is characterized by severe neurological symptoms, clinically presenting as Sanfilippo syndrome, for which no effective therapy is available. The lysosomal SGSH enzyme is conserved in Drosophila and we have identified increased levels of heparan sulfate in flies with ubiquitous knockdown of SGSH/CG14291. Using neuronal specific knockdown of SGSH/CG14291 we have also observed a h...
Source: Experimental Neurology - February 1, 2018 Category: Neurology Authors: Webber DL, Choo A, Hewson LJ, Trim PJ, Snel MF, Hopwood JJ, Richards RI, Hemsley KM, O'Keefe LV Tags: Exp Neurol Source Type: research

Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats.
In this study, we investigated the effects of epothilone D (Epo D), an analog of Epo B with a possible greater therapeutic index, on fibrotic scarring, axonal sprouting and functional recovery after SCI. Delayed systemic administration of Epo D after a moderate contusion injury (150 kDyn) in female Fischer 344 rats resulted in a reduced number of footfalls when crossing a horizontal ladder at 4 and 8 weeks post-injury. Hindlimb motor function assessed with the BBB open field locomotor rating scale and Catwalk gait analysis were not significantly altered. Moreover, formation of laminin positive fibrotic scar tissue and ...
Source: Experimental Neurology - February 1, 2018 Category: Neurology Authors: Sandner B, Puttagunta R, Motsch M, Bradke F, Ruschel J, Blesch A, Weidner N Tags: Exp Neurol Source Type: research

Dissipation of transmembrane potassium gradient is the main cause of cerebral ischemia-induced depolarization in astrocytes and neurons.
Abstract Membrane potential (VM) depolarization occurs immediately following cerebral ischemia and is devastating for the astrocyte homeostasis and neuronal signaling. Previously, an excessive release of extracellular K+ and glutamate has been shown to underlie an ischemia-induced VM depolarization. Ischemic insults should impair membrane ion channels and disrupt the physiological ion gradients. However, their respective contribution to ischemia-induced neuronal and glial depolarization and loss of neuronal excitability are unanswered questions. A short-term oxygen-glucose deprivation (OGD) was used for the purpos...
Source: Experimental Neurology - January 30, 2018 Category: Neurology Authors: Du Y, Wang W, Lutton AD, Kiyoshi CM, Ma B, Taylor AT, Olesik JW, McTigue DM, Askwith CC, Zhou M Tags: Exp Neurol Source Type: research

TREM2 overexpression attenuates neuroinflammation and protects dopaminergic neurons in experimental models of Parkinson's disease.
Abstract Triggering receptor expressed on myeloid cells-2 (TREM2) was a newly identified receptor expressed on microglia. Several observations support the hypothesis that TREM2 variation may confer susceptibility to Parkinson's disease (PD). Therefore, in this paper, we explored the role of TREM2 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Our results revealed that overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo. Further mechanistic study revealed that TREM2 inhibited neuroinflammatio...
Source: Experimental Neurology - January 27, 2018 Category: Neurology Authors: Ren M, Guo Y, Wei X, Yan S, Qin Y, Zhang X, Jiang F, Lou H Tags: Exp Neurol Source Type: research

Diverse functions of protein tyrosine phosphatase σ in the nervous and immune systems.
Diverse functions of protein tyrosine phosphatase σ in the nervous and immune systems. Exp Neurol. 2018 Jan 25;: Authors: Ohtake Y, Saito A, Li S Abstract Tyrosine phosphorylation is a common means of regulating protein functions and signal transduction in multiple cells. Protein tyrosine phosphatases (PTPs) are a large family of signaling enzymes that remove phosphate groups from tyrosine residues of target proteins and change their functions. Among them, receptor-type PTPs (RPTPs) exhibit a distinct spatial pattern of expression and play essential roles in regulating neurite outgrowth, axon gu...
Source: Experimental Neurology - January 25, 2018 Category: Neurology Authors: Ohtake Y, Saito A, Li S Tags: Exp Neurol Source Type: research

Zn2+-induced disruption of neuronal mitochondrial function: Synergism with Ca2+, critical dependence upon cytosolic Zn2+ buffering, and contributions to neuronal injury.
Abstract Excitotoxic Zn2+ and Ca2+ accumulation contributes to neuronal injury after ischemia or prolonged seizures. Synaptically released Zn2+ can enter postsynaptic neurons via routes including voltage sensitive Ca2+ channels (VSCC), and, more rapidly, through Ca2+ permeable AMPA channels. There are also intracellular Zn2+ binding proteins which can either buffer neuronal Zn2+ influx or release bound Zn2+ into the cytosol during pathologic conditions. Studies in culture highlight mitochondria as possible targets of Zn2+; cytosolic Zn2+ can enter mitochondria and induce effects including loss of mitochondrial mem...
Source: Experimental Neurology - January 17, 2018 Category: Neurology Authors: Ji SG, Weiss JH Tags: Exp Neurol Source Type: research

Interaction of DCF1 with ATP1B1 induces impairment in astrocyte structural plasticity via the P38 signaling pathway.
Abstract Astrocytes are known to regulate and support neuronal and synaptic functions. Changes in their size and morphology in mouse models result in mental retardation. However, the mechanism underlying these morphological changes remains unclear. In the present study, abnormal astrocyte morphology was found in the mouse brain following knockout of dendritic cell factor 1 (Dcf1). Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an interaction between these two proteins, with asparagine residue 266 of ATP1B1 ...
Source: Experimental Neurology - January 12, 2018 Category: Neurology Authors: Wang J, Zhou F, Wang D, Li J, Lu D, Li Q, Zhou H, Li W, Wang Q, Wu Y, Xie J, Wen T Tags: Exp Neurol Source Type: research

Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT1A receptor biased agonists.
Abstract Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistent...
Source: Experimental Neurology - January 12, 2018 Category: Neurology Authors: Brys I, Halje P, Scheffer-Teixeira R, Varney M, Newman-Tancredi A, Petersson P Tags: Exp Neurol Source Type: research

Upregulation of NLRP3 via STAT3-dependent histone acetylation contributes to painful neuropathy induced by bortezomib.
Abstract Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bort...
Source: Experimental Neurology - January 12, 2018 Category: Neurology Authors: Liu CC, Huang ZX, Li X, Shen KF, Liu M, Ouyang HD, Zhang SB, Ruan YT, Zhang XL, Wu SL, Xin WJ, Ma C Tags: Exp Neurol Source Type: research

The role of Hedgehog-responsive fibroblasts in facial nerve regeneration.
CONCLUSION: These findings describe a key signaling pathway by which fibroblasts participate in motor nerve regeneration. Fibroblasts that reside within the nerve respond to injury and may represent a novel therapeutic target in the context of facial nerve regeneration after transection injury. PMID: 29337143 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Bobarnac Dogaru GL, Juneja SC, Shokrani A, Hui RY, Chai Y, Pepper JP Tags: Exp Neurol Source Type: research

Early activation of Egr-1 promotes neuroinflammation and dopaminergic neurodegeneration in an experimental model of Parkinson's disease.
Abstract The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak indu...
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Yu Q, Huang Q, Du X, Xu S, Li M, Ma S Tags: Exp Neurol Source Type: research

Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating G αi/Gαq-CK2 signaling in ischemic stroke.
Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Gαi/Gαq-CK2 signaling in ischemic stroke. Exp Neurol. 2018 Jan 11;: Authors: Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y, Bai B Abstract Cerebral ischemia/reperfusion (I/R) injury-induced neuronal apoptosis contributes to the death and disability in patients with ischemic stroke. However, underlying mechanisms remain elusive and it lacks effective treatment. Here we reported that the expression of casein kinase 2 (CK2) was significantly reduced in brains of middle cerebral artery occlusion/reperfusion (MACO/R) model ra...
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y, Bai B Tags: Exp Neurol Source Type: research

Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of cell bodies, dendrites, and axons.
Abstract Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood (Gutilla et al., 2016). Here, we assessed whether PTEN deletion in adult mice would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5 of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN's identified by tdT expression and retrograde labeling with fluorogold (FG) were significantly enlarged four months following PTEN deletion, and c...
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Gallent EA, Steward O Tags: Exp Neurol Source Type: research

An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites.
Abstract Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4-/- neonates in vivo compared with Nrg4+/+ littermates. Neocortical pyramidal neurons cultured from Nrg4-/- embryos had significantly shorter and l...
Source: Experimental Neurology - January 6, 2018 Category: Neurology Authors: Paramo B, Wyatt S, Davies AM Tags: Exp Neurol Source Type: research

Activation of NPY-Y2 receptors ameliorates disease pathology in the R6/2 mouse and PC12 cell models of Huntington's disease.
Abstract Huntington's disease (HD) is a monogenic inherited polyglutamine-mediated neurodegenerative disorder for which effective therapies are currently unavailable. Neuropeptide Y (NPY) has been implicated as a potential therapeutic target in several neurodegenerative diseases, including HD. However, its mechanisms of action in the context of HD pathology remain unknown. Here, we investigated the beneficial effects of Y2 receptor (Y2R) activation with NPY or Y2R selective agonist NPY13-36 in the R6/2 mouse and PC12 cell models of HD. Also, we explored the effects of selective pharmacological blockage of Y2R usin...
Source: Experimental Neurology - January 5, 2018 Category: Neurology Authors: Fatoba O, Kloster E, Reick C, Saft C, Gold R, Epplen JT, Arning L, Ellrichmann G Tags: Exp Neurol Source Type: research

Decreased glutathione levels cause overt motor neuron degeneration in hSOD1WT over-expressing mice.
Abstract Mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. Several lines of evidence have shown that SOD1 mutations cause ALS through a gain of a toxic function that remains to be fully characterized. A significant share of our understanding of the mechanisms underlying the neurodegenerative process in ALS comes from the study of rodents over-expressing ALS-linked mutant hSOD1. These mutant hSOD1 models develop an ALS-like phenotype. On the other hand, hemizygous mice over-expressing w...
Source: Experimental Neurology - January 4, 2018 Category: Neurology Authors: Killoy KM, Harlan BA, Pehar M, Helke KL, Johnson JA, Vargas MR Tags: Exp Neurol Source Type: research

Neuroprotective effect of acute ethanol intoxication in TBI is associated to the hierarchical modulation of early transcriptional responses.
, Roselli F Abstract Ethanol intoxication is a risk factor for traumatic brain injury (TBI) but clinical evidence suggests that it may actually improve the prognosis of intoxicated TBI patients. We have employed a closed, weight-drop TBI model of different severity (2cm or 3cm falling height), preceded (-30min) or followed (+20min) by ethanol administration (5g/Kg). This protocol allows us to study the interaction of binge ethanol intoxication in TBI, monitoring behavioral changes, histological responses and the transcriptional regulation of a series of activity-regulated genes (immediate early genes, IEGs). We de...
Source: Experimental Neurology - January 4, 2018 Category: Neurology Authors: Chandrasekar A, Aksan B, Heuvel FO, Förstner P, Sinske D, Rehman R, Palmer A, Ludolph A, Huber-Lang M, Böckers T, Mauceri D, Knöll B, Roselli F Tags: Exp Neurol Source Type: research

The involvement of the pathway connecting the substantia nigra, the periaqueductal gray matter and the retrotrapezoid nucleus in breathing control in a rat model of Parkinson's disease.
Abstract Parkinson's disease (PD) is characterized by a reduction in the number of dopaminergic neurons of the substantia nigra (SNpc), accompanied by motor and non-motor deficiencies such as respiratory failure. Here, our aim was to investigate possible neuronal communications between the SNpc and chemoreceptor neurons within the retrotrapezoid nucleus (RTN), in order to explain neurodegeneration and the loss of breathing function in the 6-OHDA PD animal model. Male Wistar rats received tracer injections in the SNpc, RTN and periaqueductal gray (PAG) regions to investigate the projections between those regions. T...
Source: Experimental Neurology - January 3, 2018 Category: Neurology Authors: Lima JC, Oliveira LM, Botelho MT, Moreira TS, Takakura AC Tags: Exp Neurol Source Type: research

Intraspinal microstimulation for respiratory muscle activation.
Abstract A complex propriospinal network is synaptically coupled to phrenic and intercostal motoneurons, and this makes it difficult to predict how gray matter intraspinal microstimulation (ISMS) will recruit respiratory motor units. We therefore mapped the cervical and high thoracic gray matter at locations which ISMS activates diaphragm (DIA) and external intercostal (EIC) motor units. Respiratory muscle electromyography (EMG) was recorded in anesthetized female spinally intact adult rats while a stimulating electrode was advanced ventrally into the spinal cord in 600μm increments. At each depth, single bipha...
Source: Experimental Neurology - January 2, 2018 Category: Neurology Authors: Sunshine MD, Ganji CN, Reier PJ, Fuller DD, Moritz CT Tags: Exp Neurol Source Type: research

Interneuron synaptopathy in developing rat cortex induced by the pro-inflammatory cytokine LIF.
S, Wahle P PMID: 29305051 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 2, 2018 Category: Neurology Authors: Engelhardt M, Hamad MIK, Jack A, Ahmed K, König J, Rennau LM, Jamann N, Räk A, Schönfelder S, Riedel C, Wirth MJ, Patz S, Wahle P Tags: Exp Neurol Source Type: research

Editorial for "Experimental Approaches to Advance Therapies for Tumors of the Central and Peripheral Nervous System".
Editorial for "Experimental Approaches to Advance Therapies for Tumors of the Central and Peripheral Nervous System". Exp Neurol. 2018 Jan;299(Pt B):267-269 Authors: PMID: 29249264 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - December 19, 2017 Category: Neurology Tags: Exp Neurol Source Type: research

Animal models in autism research: The legacy of Paul H. Patterson.
PMID: 29223411 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - December 12, 2017 Category: Neurology Authors: Pardo CA, Meffert MK Tags: Exp Neurol Source Type: research

Systemic administration of epothilone D improves functional recovery of walking after rat spinal cord contusion injury.
Abstract Central nervous system (CNS) injuries cause permanent impairments of sensorimotor functions as mature neurons fail to regenerate their severed axons. The poor intrinsic growth capacity of adult CNS neurons and the formation of an inhibitory lesion scar are key impediments to axon regeneration. Systemic administration of the microtubule stabilizing agent epothilone B promotes axon regeneration and recovery of motor function by activating the intrinsic axonal growth machinery and by reducing the inhibitory fibrotic lesion scar. Thus, epothilones hold clinical promise as potential therapeutics for spinal cor...
Source: Experimental Neurology - December 6, 2017 Category: Neurology Authors: Ruschel J, Bradke F Tags: Exp Neurol Source Type: research

Translating scientific advances into disease-modifying therapies for Parkinson's Disease.
PMID: 29145992 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - November 18, 2017 Category: Neurology Authors: Cenci MA, Olanow CW Tags: Exp Neurol Source Type: research

Is more always better? How different 'doses' of exercise after incomplete spinal cord injury affects the membrane properties of deep dorsal horn interneurons.
Abstract Interneurons in the deep dorsal horn (DDH) of the spinal cord process somatosensory input, and form an important link between upper and lower motoneurons to subsequently shape motor output. Exercise training after SCI is known to improve functional motor recovery, but little is known about the mechanisms within spinal cord neurons that underlie these improvements. Here we investigate how the properties of DDH interneurons are affected by spinal cord injury (SCI) alone, and SCI in combination with different 'doses' of treadmill exercise training (3, 6, and 9wks). In an adult mouse hemisection model of SCI ...
Source: Experimental Neurology - November 13, 2017 Category: Neurology Authors: Rank MM, Galea MP, Callister R, Callister RJ Tags: Exp Neurol Source Type: research

Inhibition of Rac1 ameliorates neuronal oxidative stress damage via reducing Bcl-2/Rac1 complex formation in mitochondria through PI3K/Akt/mTOR pathway.
In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria. Furthermore, the levels of p-PI3K, p-Akt and p-mTOR increased, while 8-OHdG, ROS...
Source: Experimental Neurology - November 9, 2017 Category: Neurology Authors: Pan Y, Wang N, Xia P, Wang E, Guo Q, Ye Z Tags: Exp Neurol Source Type: research

Combined administration of resolvin E1 and lipoxin A4 resolves inflammation in a murine model of Alzheimer's disease.
In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aβ pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1.5 μg/kg, 3 times a week until 3months of age. We found that treatment with RvE1 or LXA4 alone or in combination increase...
Source: Experimental Neurology - November 7, 2017 Category: Neurology Authors: Kantarci A, Aytan N, Palaska I, Stephens D, Crabtree L, Benincasa C, Jenkins BG, Carreras I, Dedeoglu A Tags: Exp Neurol Source Type: research

Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury.
This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: -30%) and external capsule (EC: -21%). Parallel neuropathological studies indicated reduction in neuronal density,...
Source: Experimental Neurology - November 7, 2017 Category: Neurology Authors: Pischiutta F, Micotti E, Hay JR, Marongiu I, Sammali E, Tolomeo D, Vegliante G, Stocchetti N, Forloni G, De Simoni MG, Stewart W, Zanier ER Tags: Exp Neurol Source Type: research

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.
Abstract The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. I...
Source: Experimental Neurology - November 7, 2017 Category: Neurology Authors: Wang YY, Wang Y, Jiang HF, Liu JH, Jia J, Wang K, Zhao F, Luo MH, Luo MM, Wang XM Tags: Exp Neurol Source Type: research

Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis.
Abstract In the United States, perinatal brain injury (PBI) is a major cause of infant mortality and childhood disability. For a large proportion of infants with PBI, central nervous system (CNS) injury begins in utero with inflammation (chorioamnionitis/CHORIO) and/or hypoxia-ischemia. While studies show CHORIO contributes to preterm CNS injury and is also a common independent risk factor for brain injury in term infants, the molecular mechanisms mediating inflammation in the placental-fetal-brain axis that result in PBI remain a gap in knowledge. The chemokine (C-X-C motif) ligand 1 (CXCL1), and its cognate rece...
Source: Experimental Neurology - November 5, 2017 Category: Neurology Authors: Yellowhair TR, Noor S, Maxwell JR, Anstine CV, Oppong AY, Robinson S, Milligan ED, Jantzie LL Tags: Exp Neurol Source Type: research

Newfound sex differences in axonal structure underlie differential outcomes from in vitro traumatic axonal injury.
th DH Abstract Since traumatic axonal injury (TAI) is implicated as a prominent pathology of concussion, we examined potential sex differences in axon structure and responses to TAI. Rat and human neurons were used to develop micropatterned axon tracts in vitro that were genetically either "male" or "female". Ultrastructural analysis revealed for the first time that female axons were consistently smaller with fewer microtubules than male axons. Computational modeling of TAI showed that these structural differences place microtubules in female axons at greater risk of rupture during trauma under...
Source: Experimental Neurology - November 2, 2017 Category: Neurology Authors: Dollé JP, Jaye A, Anderson SA, Ahmadzadeh H, Shenoy VB, Smith DH Tags: Exp Neurol Source Type: research

Lowered iPLA2 γ activity causes increased mitochondrial lipid peroxidation and mitochondrial dysfunction in a rotenone-induced model of Parkinson's disease.
Lowered iPLA2γ activity causes increased mitochondrial lipid peroxidation and mitochondrial dysfunction in a rotenone-induced model of Parkinson's disease. Exp Neurol. 2017 Nov 02;: Authors: Chao H, Liu Y, Fu X, Xu X, Bao Z, Lin C, Li Z, Liu Y, Wang X, You Y, Liu N, Ji J Abstract iPLA2γ, calcium-independent phospholipase A2γ, discerningly hydrolyses glycerophospholipids to liberate free fatty acids. iPLA2γ-deficiency has been associated with abnormal mitochondrial function. More importantly, the iPLA2 family is causative proteins in mitochondrial neurodegenerative disorders suc...
Source: Experimental Neurology - November 2, 2017 Category: Neurology Authors: Chao H, Liu Y, Fu X, Xu X, Bao Z, Lin C, Li Z, Liu Y, Wang X, You Y, Liu N, Ji J Tags: Exp Neurol Source Type: research

Putative roles of soluble trophic factors in facial nerve regeneration, target reinnervation, and recovery of vibrissal whisking.
Abstract It is well-known that, after nerve transection and surgical repair, misdirected regrowth of regenerating motor axons may occur in three ways. The first way is that the axons enter into endoneurial tubes that they did not previously occupy, regenerate through incorrect fascicles and reinnervate muscles that they did not formerly supply. Consequently the activation of these muscles results in inappropriate movements. The second way is that, in contrast with the precise target-directed pathfinding by elongating motor nerves during embryonic development, several axons rather than a single axon grow out from e...
Source: Experimental Neurology - November 2, 2017 Category: Neurology Authors: Bendella H, Rink S, Grosheva M, Sarikcioglu L, Gordon T, Angelov DN Tags: Exp Neurol Source Type: research

Retraction notice to "Exploring the mechanism by which accumbal deep brain stimulation attenuates morphine-induced reinstatement through manganese-enhanced MRI and pharmacological intervention" Experimental Neurology 290 (2017) 29-40.
Retraction notice to "Exploring the mechanism by which accumbal deep brain stimulation attenuates morphine-induced reinstatement through manganese-enhanced MRI and pharmacological intervention" Experimental Neurology 290 (2017) 29-40. Exp Neurol. 2017 Nov;297:191 Authors: Zhang L, Cui Y, Wang YC, Yin H, Zheng JM, Huang L, Zhao ZW, Li J PMID: 28942852 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - September 26, 2017 Category: Neurology Authors: Zhang L, Cui Y, Wang YC, Yin H, Zheng JM, Huang L, Zhao ZW, Li J Tags: Exp Neurol Source Type: research

Reversible induction of TDP-43 granules in cortical neurons after traumatic injury.
Abstract Traumatic brain injury (TBI) has been proposed as a risk factor for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). To determine whether TBI might trigger or exacerbate ALS-relevant pathology, we delivered a mild stab-wound injury to the motor cortex of three different ALS mouse models expressing mutations in SOD1, TDP-43 or FUS and scrutinized the effects on the formation of phospho-TDP-43 (pTDP-43) cytoplasmic granules. Stab-injury induced the formation of cytoplasmic TDP-43 granules in wt animals, peaking at 3dpi; a much larger response was seen in mutant TDP-43 mice, whose r...
Source: Experimental Neurology - September 20, 2017 Category: Neurology Authors: Wiesner D, Tar L, Linkus B, Chandrasekar A, Heuvel FO, Dupuis L, Tsao W, Wong PC, Ludolph A, Roselli F Tags: Exp Neurol Source Type: research

The role of jab1, a putative downstream effector of the neurotrophic cytokine macrophage migration inhibitory factor (MIF) in zebrafish inner ear hair cell development.
Abstract Macrophage migration inhibitory factor (MIF) is a neurotrophic cytokine essential for inner ear hair cell (HC) development and statoacoustic ganglion (SAG) neurite outgrowth, and SAG survival in mouse, chick and zebrafish. Another neurotrophic cytokine, Monocyte chemoattractant protein 1 (MCP1) is known to synergize with MIF; but MCP1 alone is insufficient to support mouse/chick SAG neurite outgrowth or neuronal survival. Because of the relatively short time over which the zebrafish inner ear develops (~30h), the living zebrafish embryo is an ideal system to examine mif and mcp1 cytokine pathways and inte...
Source: Experimental Neurology - September 16, 2017 Category: Neurology Authors: Weber LJ, Marcy HK, Shen YC, Tomkovich SE, Brooks KM, Hilk KE, Barald KF Tags: Exp Neurol Source Type: research

Insights into the structural biology of Gaucher disease.
Abstract Gaucher disease, the most common lysosomal storage disorder, is caused by mutations in the gene encoding the acid-β-glucosidase lysosomal hydrolase enzyme that cleaves glucocerebroside into glucose and ceramide. Reduced enzyme activity and impaired structural stability arise due to>300 known disease-causing mutations. Several of these mutations have also been associated with an increased risk of Parkinson disease (PD). Since the discovery of the acid-β-glucosidase X-ray structure, there have been major advances in our understanding of the structural properties of the protein. Analysis of spec...
Source: Experimental Neurology - September 15, 2017 Category: Neurology Authors: Smith L, Mullin S, Schapira AHV Tags: Exp Neurol Source Type: research