Abstract:
:In amyotrophic lateral sclerosis (ALS), the exogenous temporal triggers that result in initial motor neuron death are not understood. Overactivation and consequent accelerated loss of vulnerable motor neurons is one theory of disease initiation. The vulnerability of motor neurons in response to chronic peripheral nerve hyperstimulation was tested in the SOD1(G93A) rat model of ALS. A novel in vivo technique for peripheral phrenic nerve stimulation was developed via intra-diaphragm muscle electrode implantation at the phrenic motor endpoint. Chronic bilateral phrenic nerve hyperstimulation in SOD1(G93A) rats accelerated disease progression, including shortened lifespan, hastened motor neuron loss and increased denervation at diaphragm neuromuscular junctions. Hyperstimulation also resulted in focal decline in adjacent forelimb function. These results show that peripheral phrenic nerve hyperstimulation accelerates cell death of vulnerable spinal motor neurons, modifies both temporal and anatomical onset of disease, and leads to involvement of disease in adjacent anatomical regions in this ALS model.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Lepore AC,Tolmie C,O'Donnell J,Wright MC,Dejea C,Rauck B,Hoke A,Ignagni AR,Onders RP,Maragakis NJdoi
10.1016/j.nbd.2010.03.021subject
Has Abstractpub_date
2010-09-01 00:00:00pages
252-64issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(10)00093-8journal_volume
39pub_type
杂志文章abstract::Cellular mechanisms play a role in conversion of the normal prion protein PrP(C) to the disease-associated protein PrP(Sc). The cells provide not only PrP(C), but also still largely undefined factors required for efficient prion replication. Previously, we have observed that interference with ERK and p38-JNK MAP kinas...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.05.014
更新日期:2013-10-01 00:00:00
abstract:UNLABELLED:Mitochondrial dysfunction is involved in the pathogenesis of motor neuron degeneration in the G93A mutant transgenic (tgmSOD1) animal model of ALS. However, it is unknown whether mitochondriopathy is a primary or secondary event. We isolated brain (BM) and spinal cord (SCM) mitochondria from 2 month old pres...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.06.003
更新日期:2011-10-01 00:00:00
abstract::In this study, we tested whether over-expressing the GABA(B) receptor R1a subtype in transgenic mouse forebrain neurons would be sufficient to induce spontaneous absence seizures. As hypothesized, these transgenic mice develop spontaneous, recurrent, bilaterally synchronous, 3-6 Hz slow spike and wave discharges betwe...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2007.01.013
更新日期:2007-05-01 00:00:00
abstract::This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the ...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.12.007
更新日期:2010-06-01 00:00:00
abstract::Increasing evidence has linked inflammatory processes to neurodegenerative disorders, including Alzheimer's and Parkinson's disease (PD). Tumor necrosis factor alpha (TNF-alpha) is a key inflammatory cytokine and several studies linked increased TNF-alpha to dopaminergic cell death in PD. The TNF-alpha promoter sequen...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.09.010
更新日期:2008-12-01 00:00:00
abstract::The worldwide proliferation of mobile phones raises the question of the effects of 900-MHz electromagnetic fields (EMF) on the brain. Using a head-only exposure device in the rat, we showed that a 15-min exposure to 900-MHz pulsed microwaves at a high brain-averaged power of 6 W/kg induced a strong glial reaction in t...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.07.004
更新日期:2004-12-01 00:00:00
abstract::Disturbances in central serotonergic systems have been hypothesized to be involved in seasonal affective disorder (SAD). Association between SAD and the shorter allele of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR) has been reported in an American sample. We have genotyped 82 SAD patients ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2000.0373
更新日期:2001-04-01 00:00:00
abstract::Huntington's disease (HD) is a late-onset neurodegenerative disease for which the mutation is CAG/polyglutamine repeat expansion. The R6 mouse lines expressing the HD mutation develop a movement disorder that is preceded by the formation of neuronal polyglutamine aggregates. The phenotype is likely caused by a widespr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2001.0430
更新日期:2001-10-01 00:00:00
abstract::Intraneocortical injection of ibotenate, a glutamate analog, in newborn mice produces damage mimicking lesions observed in human infants with cerebral palsy. Previous research using this model has demonstrated that pretreatment with IL-9, a Th2 cytokine, significantly exacerbated excitotoxic brain lesions. The goal of...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.09.018
更新日期:2005-02-01 00:00:00
abstract::We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.10.001
更新日期:2013-03-01 00:00:00
abstract::Excitotoxicity plays a central role in the neuronal damage during ischemic stroke. Although growing evidence suggests that activation of extrasynaptic NMDA receptors initiates neuronal death, no direct evidence demonstrated their activation during ischemia. Using rat hippocampal slices, we detected oxygen-glucose depr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.05.005
更新日期:2013-10-01 00:00:00
abstract::Frontotemporal dementia (FTD) is one of the most prevalent forms of early-onset dementia. It represents part of the FTD-Amyotrophic Lateral Sclerosis (ALS) spectrum, a continuum of genetically and pathologically overlapping disorders. FTD-causing mutations in CHMP2B, a gene encoding a core component of the heteromeric...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105047
更新日期:2020-10-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. Although 10% of ALS cases are familial (FALS), the majority are sporadic (SALS) and probably associated to a multifactorial etiology. Currently ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.12.002
更新日期:2015-02-01 00:00:00
abstract::Neuropeptide Y (NPY) is an important 36 amino acid peptide that is abundantly expressed in the mammalian CNS and is known to be an endogenous modulator of seizure activity, including in rat models of Genetic Generalised Epilepsy (GGE) with absence seizures. Studies have shown that viral-mediated "gene therapy" with ov...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.01.016
更新日期:2018-05-01 00:00:00
abstract::Deregulation of intracellular calcium homeostasis is widely considered as one of the underlying pathophysiological mechanisms of hypoxic-ischemic brain injury. Whether this alteration can result in cerebral calcification was investigated in basal ganglia, cerebral cortex, and hippocampus of human premature and term ne...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2000.0332
更新日期:2001-02-01 00:00:00
abstract::Polyglutamine neurodegenerative disorders are characterized by the expansion of a glutamine tract within the mutant disease-causing protein. Expression of the mutant protein induces a progressive loss of neuronal function and the subsequent neurodegeneration of a set of neurons characteristic to each disease. Spinocer...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.2000.0305
更新日期:2000-06-01 00:00:00
abstract::Glutamatergic dysfunction is strongly implicated in schizophrenia and mood disorders. GluA1 knockout (KO) mice display schizophrenia- and depression-related abnormalities. Here, we asked whether GluA1 KO show mania-related abnormalities. KO were tested for behavior in approach/avoid conflict tests, responses to repeat...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.08.005
更新日期:2010-12-01 00:00:00
abstract::Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105058
更新日期:2020-11-01 00:00:00
abstract::Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamu...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2014.05.010
更新日期:2014-12-01 00:00:00
abstract::Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.02.014
更新日期:2018-06-01 00:00:00
abstract::Beta power suppression in the basal ganglia is stronger during movements that require high force levels and high movement effort but it has been difficult to dissociate the two. We recorded scalp EEG and basal ganglia local field potentials in Parkinson's disease patients (11 STN, 7 GPi) ON and OFF dopaminergic medica...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.03.004
更新日期:2019-07-01 00:00:00
abstract::Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.08.001
更新日期:2013-01-01 00:00:00
abstract::It is widely accepted that the loss of function of different cellular proteins following their aggregation into highly stable aggregates or the gain of pathologic function of the resulting macromolecular assemblies or both processes are tightly associated to distinct debilitating neurodegenerative diseases such as Alz...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.03.011
更新日期:2018-01-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (Apo...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.02.005
更新日期:2006-07-01 00:00:00
abstract::Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia. To date, the pathogenesis of CADASIL remains poorly understo...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104561
更新日期:2019-12-01 00:00:00
abstract::Deep brain stimulation of certain target structures within the basal ganglia is an effective therapy for the management of the motor symptoms of Parkinson's disease. However, its mechanisms, as well as the pathophysiology of Parkinson's disease, are varied and complex. The classical model of Parkinson's disease states...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.10.020
更新日期:2019-04-01 00:00:00
abstract::Amyloid-β is a peptide released by synapses in physiological conditions and its pathological accumulation in brain structures necessary for memory processing represents a key toxic hallmark underlying Alzheimer's disease. The oligomeric form of Amyloid-β (Aβο) is now believed to represent the main Amyloid-β species af...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.07.001
更新日期:2018-10-01 00:00:00
abstract::Premature stop codons in CACNA1A, which encodes the alpha(1A) subunit of neuronal P/Q-type (Ca(V)2.1) Ca(2+) channels, cause episodic ataxia type 2 (EA2). CACNA1A undergoes extensive alternative splicing, which contributes to the pharmacological and kinetic heterogeneity of Ca(V)2.1-mediated Ca(2+) currents. We identi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.06.002
更新日期:2008-10-01 00:00:00
abstract::Alzheimer's disease (AD) involves changes in both lipid and RNA metabolism, but it remained unknown if these differences associate with AD's cognition and/or post-mortem neuropathology indices. Here, we report RNA-sequencing evidence of inter-related associations between lipid processing, cognition level, and AD neuro...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.06.008
更新日期:2017-10-01 00:00:00
abstract::Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficit...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2011.10.019
更新日期:2012-06-01 00:00:00