Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury.

Abstract:

:Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Ruitenberg MJ,Blits B,Dijkhuizen PA,te Beek ET,Bakker A,van Heerikhuize JJ,Pool CW,Hermens WT,Boer GJ,Verhaagen J

doi

10.1016/j.nbd.2003.11.018

keywords:

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

394-406

issue

2

eissn

0969-9961

issn

1095-953X

pii

S0969996103002572

journal_volume

15

pub_type

杂志文章
  • Anti-NMDA receptor autoantibodies and associated neurobehavioral pathology in mice are dependent on age of first exposure to Toxoplasma gondii.

    abstract:BACKGROUND:Toxoplasma gondii is a pathogen implicated in psychiatric disorders. As elevated antibodies to T. gondii are also present in non-symptomatic individuals, we hypothesized that the age during first exposure to the pathogen may affect symptom manifestation. We tested this hypothesis by evaluating neurobehaviora...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2016.03.005

    authors: Kannan G,Crawford JA,Yang C,Gressitt KL,Ihenatu C,Krasnova IN,Cadet JL,Yolken RH,Severance EG,Pletnikov MV

    更新日期:2016-07-01 00:00:00

  • Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

    abstract::Senile plaques composed mainly of beta-amyloid (Abeta) and neurofibrillary tangles principally composed of hyperphosphorylated tau are the major pathological features of Alzheimer's disease (AD). Despite the fact that increased expression of amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes in mice lea...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/s0969-9961(03)00084-6

    authors: Kurt MA,Davies DC,Kidd M,Duff K,Howlett DR

    更新日期:2003-10-01 00:00:00

  • Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.

    abstract::The Alzheimer disease-associated beta-amyloid peptide has been shown to induce apoptotic neuronal death. In the present study, we test the hypothesis that the apoptotic pathway activated by beta-amyloid is similar to the pathway activated by the Fas/TNFR family of death receptors, which requires caspase-8 activity and...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.1999.0268

    authors: Ivins KJ,Thornton PL,Rohn TT,Cotman CW

    更新日期:1999-10-01 00:00:00

  • Sodium butyrate triggers a functional elongation of microglial process via Akt-small RhoGTPase activation and HDACs inhibition.

    abstract::Microglia, a type of immune cell in the brain, are in a ramified status with branched processes in normal conditions. Upon pathological stimulation, microglia retract their processes and become activated. Searching methods to make the activated microglia return to ramified status would help cope with injuries induced ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2017.12.006

    authors: Wang P,Zhang Y,Gong Y,Yang R,Chen Z,Hu W,Wu Y,Gao M,Xu X,Qin Y,Huang C

    更新日期:2018-03-01 00:00:00

  • Temporal lobe epilepsy causes selective changes in mu opioid and nociceptin receptor binding and functional coupling to G-proteins in human temporal neocortex.

    abstract::There is no information concerning signal transduction mechanisms downstream of the opioid/nociceptin receptors in the human epileptic brain. The aim of this work was to evaluate the level of G-proteins activation mediated by DAMGO (a mu receptor selective peptide) and nociceptin, and the binding to mu and nociceptin ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2009.06.008

    authors: Rocha L,Orozco-Suarez S,Alonso-Vanegas M,Villeda-Hernandez J,Gaona A,Páldy E,Benyhe S,Borsodi A

    更新日期:2009-09-01 00:00:00

  • Fibrillation and molecular characteristics are coherent with clinical and pathological features of 4-repeat tauopathy caused by MAPT variant G273R.

    abstract::Microtubule Associated Protein Tau (MAPT) forms proteopathic aggregates in several diseases. The G273R tau mutation, located in the first repeat region, was found by exome sequencing in a patient who presented with dementia and parkinsonism. We herein return to pathological examination which demonstrated tau immunorea...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2020.105079

    authors: Sandberg A,Ling H,Gearing M,Dombroski B,Cantwell L,R'Bibo L,Levey A,Schellenberg GD,Hardy J,Wood N,Fernius J,Nyström S,Svensson S,Thor S,Hammarström P,Revesz T,Mok KY

    更新日期:2020-12-01 00:00:00

  • Increased mortality and spatial memory deficits in TNF-alpha-deficient mice in ceftriaxone-treated experimental pneumococcal meningitis.

    abstract::Tumor necrosis factor-alpha (TNF-alpha) is critically involved in inflammation and may participate in hippocampal injury in bacterial meningitis. In a mouse model of ceftriaxone-treated pneumococcal meningitis, spatial memory and motor performance of TNF-alpha-deficient (n = 57) and control mice (n = 55) were investig...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2004.01.013

    authors: Gerber J,Böttcher T,Hahn M,Siemer A,Bunkowski S,Nau R

    更新日期:2004-06-01 00:00:00

  • Alpha-synuclein deregulates the expression of COL4A2 and impairs ER-Golgi function.

    abstract::Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2018.08.001

    authors: Paiva I,Jain G,Lázaro DF,Jerčić KG,Hentrich T,Kerimoglu C,Pinho R,Szegő ÈM,Burkhardt S,Capece V,Halder R,Islam R,Xylaki M,Caldi Gomes LA,Roser AE,Lingor P,Schulze-Hentrich JM,Borovečki F,Fischer A,Outeiro TF

    更新日期:2018-11-01 00:00:00

  • Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE epsilon4 allele, in relation to cognitive function and cerebral glucose metabolism.

    abstract::Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying epsilon4 allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity a...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2006.07.013

    authors: Darreh-Shori T,Brimijoin S,Kadir A,Almkvist O,Nordberg A

    更新日期:2006-11-01 00:00:00

  • Adenovirus-mediated GDNF and CNTF pretreatment protects against striatal injury following transient middle cerebral artery occlusion in mice.

    abstract::During the last few years, adenoviral gene transfer techniques have achieved increasing interest in the treatment of neurodegenerative diseases. However, gene therapy requires that delivered genes are translated into proteins. This may pose a problem in focal ischemia where protein synthesis is compromized. The presen...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.2001.0399

    authors: Hermann DM,Kilic E,Kügler S,Isenmann S,Bähr M

    更新日期:2001-08-01 00:00:00

  • Functional MAPT haplotypes: bridging the gap between genotype and neuropathology.

    abstract::The microtubule-associated protein tau (MAPT) locus has long been associated with sporadic neurodegenerative disease, notably progressive supranuclear palsy and corticobasal degeneration, and more recently with Alzheimer's disease and Parkinson's disease. However, the functional biological mechanisms behind the geneti...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2007.04.006

    authors: Caffrey TM,Wade-Martins R

    更新日期:2007-07-01 00:00:00

  • Identification of novel genes and altered signaling pathways in the retinal pigment epithelium during the Royal College of Surgeons rat retinal degeneration.

    abstract::Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a circadian manner. The homozygous deletion of the c-mer gene abolishes the ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat strain, which in turn leads to the death of photoreceptor cells. We identified RPE transcr...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/s0969-9961(03)00102-5

    authors: Dufour EM,Nandrot E,Marchant D,Van Den Berghe L,Gadin S,Issilame M,Dufier JL,Marsac C,Carper D,Menasche M,Abitbol M

    更新日期:2003-11-01 00:00:00

  • Interneuronal calcium channel abnormalities in posttraumatic epileptogenic neocortex.

    abstract::Decreased release probability (Pr) and increased failure rate for monosynaptic inhibitory postsynaptic currents (IPSCs) indicate abnormalities in presynaptic inhibitory terminals on pyramidal (Pyr) neurons of the undercut (UC) model of posttraumatic epileptogenesis. These indices of inhibition are normalized in high [...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2011.11.006

    authors: Faria LC,Parada I,Prince DA

    更新日期:2012-02-01 00:00:00

  • The role of cannabinoid 1 receptor expressing interneurons in behavior.

    abstract::Schizophrenia is a devastating neurodevelopmental disorder that affects approximately 1% of the population. Reduced expression of the 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of the disease and is encoded by the GAD1 gene. In schizophrenia, GAD67 downregulation occurs in multiple int...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.11.001

    authors: Brown JA,Horváth S,Garbett KA,Schmidt MJ,Everheart M,Gellért L,Ebert P,Mirnics K

    更新日期:2014-03-01 00:00:00

  • Neuroprotective effects of erythropoietin in the rat hippocampus after pilocarpine-induced status epilepticus.

    abstract::Neuroprotective functions of erythropoietin (Epo) are thought to involve a heteroreceptor composed of both Epo receptor (Epo-R) and common beta chain (betac). Here, we measured the response of hippocampal Epo system components (Epo, Epo-R and betac) during neurodegenerative processes following pilocarpine-induced stat...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2006.10.009

    authors: Nadam J,Navarro F,Sanchez P,Moulin C,Georges B,Laglaine A,Pequignot JM,Morales A,Ryvlin P,Bezin L

    更新日期:2007-02-01 00:00:00

  • Therapeutic potential of a TrkB agonistic antibody for ischemic brain injury.

    abstract::The clinical trials employing neuroprotectants targeting single, early pathogenic mechanisms in stroke have so far been barely successful. We found in human postmortem stroke brains that in addition to apoptosis, necroptosis also contributed to neuronal damage. Thus, a new strategy targeting both mechanisms might be n...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2019.04.009

    authors: Han F,Guan X,Guo W,Lu B

    更新日期:2019-07-01 00:00:00

  • Correlation between cortical beta power and gait speed is suppressed in a parkinsonian model, but restored by therapeutic deep brain stimulation.

    abstract::The motor cortex and subthalamic nucleus (STN) of patients with Parkinson's disease (PD) exhibit abnormally high levels of electrophysiological oscillations in the ~12-35 Hz beta-frequency range. Recent studies have shown that beta is partly carried forward to regulate future motor states in the healthy condition, sug...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2018.05.013

    authors: Polar CA,Gupta R,Lehmkuhle MJ,Dorval AD

    更新日期:2018-09-01 00:00:00

  • Parkin deficiency perturbs striatal circuit dynamics.

    abstract::Loss-of-function mutations in the parkin-encoding PARK2 gene are a frequent cause of young-onset, autosomal recessive Parkinson's disease (PD). Parkin knockout mice have no nigro-striatal neuronal loss but exhibit abnormalities of striatal dopamine transmission and cortico-striatal synaptic function. How these predege...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2020.104737

    authors: Baaske MK,Kramer ER,Meka DP,Engler G,Engel AK,Moll CKE

    更新日期:2020-04-01 00:00:00

  • Elevated GDNF levels following viral vector-mediated gene transfer can increase neuronal death after stroke in rats.

    abstract::Previous studies have indicated that administration of glial cell line-derived neurotrophic factor (GDNF) counteracts neuronal death after stroke. However, in these studies damage was evaluated at most a few days after the insult. Here, we have explored the long-term consequences of two routes of GDNF delivery to the ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2003.08.002

    authors: Arvidsson A,Kirik D,Lundberg C,Mandel RJ,Andsberg G,Kokaia Z,Lindvall O

    更新日期:2003-12-01 00:00:00

  • Excitatory-inhibitory imbalance in Alzheimer's disease and therapeutic significance.

    abstract::The interplay between excitatory and inhibitory circuits underlies the brain's processes and their dysregulation has been linked to cognitive decline, psychiatric disorders and epilepsy. In patients with Alzheimer's disease (AD), an elevated occurrence of seizures has been observed in both sporadic and familial forms ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2019.04.010

    authors: Vico Varela E,Etter G,Williams S

    更新日期:2019-07-01 00:00:00

  • Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration.

    abstract::Recent studies indicate that the Parkinson's disease-linked leucine-rich repeat kinase 2 (LRRK2) modulates cytoskeletal functions by regulating actin and tubulin dynamics, thereby affecting neurite outgrowth. By interactome analysis we demonstrate that the binding of LRRK2 to tubulins is significantly enhanced by phar...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.12.019

    authors: Caesar M,Zach S,Carlson CB,Brockmann K,Gasser T,Gillardon F

    更新日期:2013-06-01 00:00:00

  • A multiomic approach to characterize the temporal sequence in Alzheimer's disease-related pathology.

    abstract::No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples,...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2018.12.009

    authors: Marttinen M,Paananen J,Neme A,Mitra V,Takalo M,Natunen T,Paldanius KMA,Mäkinen P,Bremang M,Kurki MI,Rauramaa T,Leinonen V,Soininen H,Haapasalo A,Pike I,Hiltunen M

    更新日期:2019-04-01 00:00:00

  • Impaired cognitive discrimination and discoordination of coupled theta-gamma oscillations in Fmr1 knockout mice.

    abstract::Fragile X syndrome (FXS) patients do not make the fragile X mental retardation protein (FMRP). The absence of FMRP causes dysregulated translation, abnormal synaptic plasticity and the most common form of inherited intellectual disability. But FMRP loss has minimal effects on memory itself, making it difficult to unde...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2016.01.003

    authors: Radwan B,Dvorak D,Fenton AA

    更新日期:2016-04-01 00:00:00

  • Characterization of a commonly used mouse model of SMA reveals increased seizure susceptibility and heightened fear response in FVB/N mice.

    abstract::The SMN2 transgenic mouse, Tg(SMN2)89Ahmb, has emerged as the most widely used in spinal muscular atrophy (SMA) research. Here we clone the genomic integration site of the transgene and demonstrate it to be in intron 4 of the metabotropic glutamate receptor 7 (mGluR7) gene. We found that the integration of this transg...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2011.03.002

    authors: Gogliotti RG,Lutz C,Jorgensen M,Huebsch K,Koh S,Didonato CJ

    更新日期:2011-07-01 00:00:00

  • Dopamine D2 receptor dysfunction is rescued by adenosine A2A receptor antagonism in a model of DYT1 dystonia.

    abstract::DYT1 dystonia is an inherited disease linked to mutation in the TOR1A gene encoding for the protein torsinA. Although the mechanism by which this genetic alteration leads to dystonia is unclear, multiple lines of clinical evidence suggest a link between dystonia and a reduced dopamine D2 receptor (D2R) availability. B...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2010.03.003

    authors: Napolitano F,Pasqualetti M,Usiello A,Santini E,Pacini G,Sciamanna G,Errico F,Tassone A,Di Dato V,Martella G,Cuomo D,Fisone G,Bernardi G,Mandolesi G,Mercuri NB,Standaert DG,Pisani A

    更新日期:2010-06-01 00:00:00

  • Deconstructing the neural and ionic involvement of seizure-like events in the striatal network.

    abstract::Seizures occur in the basal ganglia (BG) of epileptic patients and in animal models of epilepsy, but there is relatively little known about how these events are gated and/or propagated through this structure. Here, we present and characterize a model of in vitro seizure-like events (SLEs) in the striatum by applying c...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.11.019

    authors: Yu W,Calos M,Pilitsis J,Shin DS

    更新日期:2013-04-01 00:00:00

  • Fluoxetine in adulthood normalizes GABA release and rescues hippocampal synaptic plasticity and spatial memory in a mouse model of Down syndrome.

    abstract::Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has been repeatedly shown that Ts65Dn mice, the major animal model for DS, have severe cognitive and synaptic plasticity dysfunctions caused by excessive inhibition in their temporal lobe structures. Here we employed a multid...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.11.010

    authors: Begenisic T,Baroncelli L,Sansevero G,Milanese M,Bonifacino T,Bonanno G,Cioni G,Maffei L,Sale A

    更新日期:2014-03-01 00:00:00

  • 200-300Hz movement modulated oscillations in the internal globus pallidus of patients with Parkinson's Disease.

    abstract::Symptoms in Parkinson's Disease (PD) have been linked to oscillatory activity within the basal ganglia. In humans, such activity has been detected mainly in the local field potentials (LFPs) recorded from electrode contacts used for deep brain stimulation. Although most studies have focused on activity within the subt...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.01.020

    authors: Tsiokos C,Hu X,Pouratian N

    更新日期:2013-06-01 00:00:00

  • Respiration and ROS production in brain and spinal cord mitochondria of transgenic rats with mutant G93a Cu/Zn-superoxide dismutase gene.

    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

    authors: Panov A,Kubalik N,Zinchenko N,Hemendinger R,Dikalov S,Bonkovsky HL

    更新日期:2011-10-01 00:00:00

  • Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associated SCN1A mutation.

    abstract::Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2019.104627

    authors: Xie Y,Ng NN,Safrina OS,Ramos CM,Ess KC,Schwartz PH,Smith MA,O'Dowd DK

    更新日期:2020-02-01 00:00:00