Epidermal Growth Factor Enhances Striatal Dopaminergic Parameters in the 1‐Methyl‐4‐Phenyl‐l, 2, 3, 6‐Tetrahydropyridine‐Treated Mouse

Hadjiconstantinou, Maria; Fitkin, James G.; Dalia, Asad; Neff, Norton H.

doi:10.1111/j.1471-4159.1991.tb03776.x

Cited by 83 publications

(25 citation statements)

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“…Significantly, TGF-␣ mutant mice exhibit significant reductions in SNc DA neurons (19). Furthermore, EGF and EGFR protein levels are significantly decreased in the striatum of PD patients (2), and EGF treatment has been shown to protect DA neurons in primary VM cultures and animal models of PD (2,4,(26)(27)(28). Familial PD can be caused by mutant dysfunctional parkin (PARK2 in PD gene classification), and normal parkin (29,30) can delay EGFR internalization and degradation and promote PI3-K/Akt signaling (31).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models

Inoue

Li²,

Lee³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

153

183

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The nervous system-specific leucine-rich repeat Ig-containing protein LINGO-1 is associated with the Nogo-66 receptor complex and is endowed with a canonical EGF receptor (EGFR)-like tyrosine phosphorylation site. Our studies indicate that LINGO-1 expression is elevated in the substantia nigra of Parkinson's disease (PD) patients compared with age-matched controls and in animal models of PD after neurotoxic lesions. LINGO-1 expression is present in midbrain dopaminergic (DA) neurons in the human and rodent brain. Therefore, the role of LINGO-1 in cell damage responses of DA neurons was examined in vitro and in experimental models of PD induced by either oxidative (6-hydroxydopamine) or mitochondrial (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity. In LINGO-1 knockout mice, DA neuron survival was increased and behavioral abnormalities were reduced compared with WT. dopamine neuron ͉ substantia nigra ͉ degeneration ͉ neuroprotection ͉ axon N ew therapeutics are required that simultaneously preserve dopamine (DA) neurons and their functional connections to limit or eliminate the progression of the movement disorder of Parkinson's disease (PD) (1, 2). Several growth factors normally active in cell growth and survival during brain development have been shown to provide protection against cell death in animal models of PD (1-5). The phosphoinositide 3-kinases (PI3-Ks) and Akt (protein kinase B) signaling pathways have been shown to participate in such growth factor actions (1, 2, 5, 6). Recent studies also suggest that some leucine-rich repeat (LRR) Ig-containing proteins can influence growth factors by modulating EGF receptor (EGFR) signaling-related pathways (7,8). LINGO-1 is a LRR-Ig protein first identified as a critical component of the NogoR1-p75NTR complex in RhoA activation, and it is responsible for some inhibition of axonal regeneration by myelin-associated factors (9, 10). Unlike NogoR1, LINGO-1 gene expression is increased when adult nerve cells are exposed to traumatic injuries (9), indicating that LINGO-1 may be involved in cell injury responses. LRRK2, another LRR protein, was recently genetically linked to PD and Lewy body disease (11, 12). As we describe here, LINGO-1 appears to regulate neurite growth and the structural integrity of neurons, in analogy with LRRK2 (9, 13).In this study, elevated LINGO-1 levels were found after selective experimental damage to DA nerve terminals in the striatum of mice, and increased expressed levels of LINGO-1 were found in the substantia nigra (SN) of some PD patients. Using methods that reduced or eliminated the negative actions of LINGO-1, we demonstrate that midbrain DA neuron survival, growth, and function improve in primary in vitro cultures and in vivo experimental models of parkinsonism in mice. We also show that LINGO-1 normally binds to EGFR and negatively regulates the EGFR/Akt signaling pathway in cells and tissues relevant to these studies. Fig. 4 B and C). LINGO-1 is expressed in remaining DA neurons in the SN of PD patients (SI Fig. 4 A and B)....

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Section: Discussionmentioning

confidence: 99%

Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models

Inoue

Li²,

Lee³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

153

183

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“…The effects of 6-OHDA (SOD), by scavenging superoxide radicals, dramatically inon both the central and peripheral catecholaminergic pathways hibits the oxidation of 6-OHDA (39). Subsequent studies in rodents and in a variety of cultured cell types have been re-have confirmed the production of superoxide radicals, and viewed elsewhere, as well as the molecular basis for its speci-have moreover demonstrated that superoxide radicals generficity (45,46,65). 6-OHDA can be administered to rodents via ated by the first step of 6-OHDA oxidation are critical in a variety of different routes, but its proper utilization in vivo propagating the oxidation of 6-OHDA (11,30,31,80 This shows that the oxidation of 2 moles of 6-OHDA leads to THE HERBICIDE PARAQUAT the formation of 2 moles of quinone and 2 moles of H,0 2 .…”

Section: Still In the Racementioning

confidence: 99%

“…PRZEDBORSKI AND ISCHIROPOULOS the pathogenesis of the disease have emerged from studies and in vitro relies on one's knowledge of a series of technical probing the functions of genes implicated in inherited forms points that have been discussed in detail (45,46,65). Because of PD and from animal and cellular model systems of PD.…”

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confidence: 99%

Role of Inflammation in MPTP-Induced Dopaminergic Degeneration

Przedborski¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of Information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302 Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. se. TASK NUMBER 5f. WORK UNIT NUMBER REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERColumbia University New York, NY 10032 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTWe are investigating the role of inflammation in the death of the dopamine (DA) neuron in the substantia nigra of MPTPtreated mice. Studies in our model over the course of this program project show that microglia are the source of superoxide and nitric oxide through up-regulation of the microglial enzymes NADPH oxidase and inducible nitric oxide synthase (iNOS). We show that activation of microglia in vivo occurs as early as 24 hours after MPTP administration at which time the presence of superoxide in the SNpc after MPTP is noted using hydroethidium histochemistry. M40401, a nonpeptidyl SOD mimetic with catalytic activity equal to or greater than native MnSOD decreased the presence of superoxide and attenuated microglial activation in the SNpc of our mice. Minocycline, a second generation antibiotic, inhibited iNOS up-regulation and also reduced microglial activation. Further, we demonstrate that cyclooxygenase-2 is a part of the inflammatory response in MPTP-treated mice. Our neuronal/microglial cultures now that they are up and running, should give a more exact timeframe of microglial activation in relation to DA neuron death in the MPTP mouse model of PD. Furthermore, we identify components of microglia that may be therapeutic targets. Parkinson's disease (PD) is a common neurodegenerative disorder characterized behaviorally by resting tremor, rigidity, akinesialbradykinesia and postural instability (Fahn and Przedborski, 2000). Neurons associated with the behavioral component of PD are mainly, though not exclusively, the dopaminergic (DA) ...

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“…De hecho, se demostró que actúa como un factor neurotrófico sobre neuronas cultivadas de la corteza cerebral, del telencéfalo subneocortical y del cerebelo, incrementando el crecimiento neurona1 y la supervivencia (5-7). Su acción neurotrófica sobre las neuronas dopaminérgicas se describió como un incremento de la supervivencia y de la maduración (8,9).…”

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Acción del factor de crecimiento epidérmico sobre el desarrollo de las células estriatales cultivadas

et al. 1996

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ResumenEn este trabajo se describe la acción del factor de crecimiento epidérmico (FCE) sobre las células del estriado embrionario en un sistema de cultivo disociado de neuronas y glías. El cultivo de células se preparó a partir de embriones de ratas de 16-17 días. En el sistema de cultivo empleado, la población celular fue cultivada durante 20-24 horas en un medio que contenía suero y, posteriormente, fue tratada con 20 ng/mL del FCE en un medio libre de suero. La eliminación del suero en este período inicial de desarrollo provocó una disminución apreciable de las células vivas en los cultivos tratados y en los controles. Al parecer, la población de células sobrevivientes estaba integrada, en su mayoría, por precursores celulares teniendo en cuenta su capacidad proliferativa. La acción del FCE sobre las células se manifestó en un aumento del número de células debido fundamentalmente a un estímulo de la proliferación de los precursores neuronales y astrocitos. Este efecto estuvo acompañado por una reducción de la diferenciación morfológica neuronal cuando se comparó con los cultivos controles. En los cultivos, a los 16 días, la detección de la actividad específica de la colina acetiltrasferasa evidenció la diferenciación de una subpoblación neuronal colinérgica, las cuales respondieron al tratamiento con el factor de crecimiento nervioso con un aumento de la actividad de la enzima. SummaryThis paper describes the effect of epidermal growth factor (EGF) on embryonic striatal cells in mixed neuronal-glial cultures prepared from 16-17 day old rat embryos. In the culture system employed, cell population was cultured for 20-24 hours in serum supplemented medium prior to being treated with 20 ng/mL epidermal growth factor (EGF) serum-free medium. This early withdrawal of serum from the culture medium caused an appreciable decline of viable cells in both control and treated cultures. It seems that the majority of surviving cells were precursors, taking into account their proliferative capacity. EGF action on cell population provoked an increase in cell numbers, mainly due to the stimulation of neuronal precursor and and astrocyte proliferation. This increase in cell proliferation was accompanied by neuronal morphological differentiation delay when compared to control cultures. Choline acetyltransferase specific activity detected in 16-day old cultures, showed the differentiation of a cholinergic neuronal subpopulation, which responded to nerve growth factor treatment with enhanced enzyme activity.

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Epidermal Growth Factor Enhances Striatal Dopaminergic Parameters in the 1‐Methyl‐4‐Phenyl‐l, 2, 3, 6‐Tetrahydropyridine‐Treated Mouse

Cited by 83 publications

References 27 publications

Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models

Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models

Role of Inflammation in MPTP-Induced Dopaminergic Degeneration

Acción del factor de crecimiento epidérmico sobre el desarrollo de las células estriatales cultivadas

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