Reduced Nurrl Expression Increases the Vulnerability of Mesencephalic Dopamine Neurons to MPTP‐Induced Injury

Le, Wei Dong; Conneely, Orla M.; He, Yanlin; Jankovic, Joseph; Appel, Stanley H.

doi:10.1046/j.1471-4159.1999.02218.x

Cited by 155 publications

(4 citation statements)

References 24 publications

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“…Studies in Nurr1-deficient mice (±) indicate that the amount of Nurr1 is important to keep homeostasis during the life of dopamine neurons (Le et al, 1999; Jiang et al, 2005; Eells et al, 2006; Zhang et al, 2012). For instance, aged Nurr1 (±) mice have a significant decrease in rotarod performance and locomotor activity, a motor impairment analogous to Parkinson's disease associated with decreased dopamine levels in the striatum (Jiang et al, 2005).…”

Section: Nur Transcription Factors and Dopaminergic Transmissionmentioning

confidence: 99%

Nur transcription factors in stress and addiction

Campos-Melo

Galleguillos

Sánchez

et al. 2013

Front. Mol. Neurosci.

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The Nur transcription factors Nur77 (NGFI-B, NR4A1), Nurr1 (NR4A2), and Nor-1 (NR4A3) are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal (HPA) axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction.

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Section: Nur Transcription Factors and Dopaminergic Transmissionmentioning

confidence: 99%

Nur transcription factors in stress and addiction

Campos-Melo

Galleguillos

Sánchez

et al. 2013

Front. Mol. Neurosci.

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“…However, MK-801 treatment in combination with l -DOPA in 6-OHDA lesioned rats increased the release of dopamine in lesioned striatum as compared to intact striatum, indicating that the effect of MK-801 on release of dopamine in striatum or SNpc depend upon the integrity of nigrostriatal pathway . The mesencephalic DAergic neurons with reduced Nurr-1 expression have been shown to be more vulnerable to MPTP-induced injury . Previous studies have shown that Nurr-1 and Pitx-3 are essentially involved in the long term survival and terminal differential of DAergic neurons , and the deficiency of Pitx-3 is reported to be responsible for the loss of TH expression in SNpc .…”

Section: Resultsmentioning

confidence: 99%

MK-801 (Dizocilpine) Regulates Multiple Steps of Adult Hippocampal Neurogenesis and Alters Psychological Symptoms via Wnt/β-Catenin Signaling in Parkinsonian Rats

Singh

Mishra

Srivastava

et al. 2016

ACS Chem. Neurosci.

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Adult hippocampal neurogenesis is directly involved in regulation of stress, anxiety, and depression that are commonly observed nonmotor symptoms in Parkinson's disease (PD). These symptoms do not respond to pharmacological dopamine replacement therapy. Excitotoxic damage to neuronal cells by N-methyl-d-aspartate (NMDA) receptor activation is also a major contributing factor in PD development, but whether it regulates hippocampal neurogenesis and nonmotor symptoms in PD is yet unexplored. Herein, for the first time, we studied the effect of MK-801, an NMDA receptor antagonist, on adult hippocampal neurogenesis and behavioral functions in 6-OHDA (6-hydroxydopamine) induced rat model of PD. MK-801 treatment (0.2 mg/kg, ip) increased neural stem cell (NSC) proliferation, self-renewal capacity, long-term survival, and neuronal differentiation in the hippocampus of rat model of PD. MK-801 potentially enhanced long-term survival, improved dendritic arborization of immature neurons, and reduced 6-OHDA induced neurodegeneration via maintaining the NSC pool in hippocampus, leading to decreased anxiety and depression-like phenotypes in the PD model. MK-801 inhibited glycogen synthase kinase-3β (GSK-3β) through up-regulation of Wnt-3a, which resulted in the activation of Wnt/β-catenin signaling leading to enhanced hippocampal neurogenesis in PD model. Additionally, MK-801 treatment protected the dopaminergic (DAergic) neurons in the nigrostriatal pathway and improved motor functions by increasing the expression of Nurr-1 and Pitx-3 in the PD model. Therefore, MK-801 treatment serves as a valuable tool to enhance hippocampal neurogenesis in PD, but further studies are needed to revisit the role of MK-801 in the neurodegenerative disorder before proposing a potential therapeutic candidate.

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“…Furthermore, the expression of the positive genetic marker for DA neurons, tyrosine hydroxylase (TH), a rate-limiting enzyme in dopamine synthesis (Daadi and Weiss, 1999;Sonntag et al, 2004;Kirkeby et al, 2017a), and the levels of GIRK2 have also been observed in many cell types in vitro (Thompson et al, 2005;Kirkeby et al, 2012;Reyes et al, 2012;Grow et al, 2016). Moreover, common positive markers used to isolate high-quality DA progenitor cells include EN1 and SPRY1 (Simon et al, 2001;Alberi et al, 2004;Kirkeby et al, 2017a); Nurr1 (Le et al, 1999); FOXA2, LMX1B, and MSX1 (Andersson et al, 2006;Chung et al, 2011), and the bicoid-related homeodomain factor Ptx3/Pitx3 (Hargus et al, 2010). It is noteworthy that some discrepancies have been found with the requirement for the presence of floor plate-specific cell surface marker CORIN expression (Ono et al, 2007;Chung et al, 2011;Kriks et al, 2011;Kirkeby et al, 2012Kirkeby et al, , 2017aDoi et al, 2014;Arenas et al, 2015;Fan et al, 2020).…”

Section: Assessment Of the Efficacy Of Cell Transplants With Immunostmentioning

confidence: 99%

Current Status of Stem Cell-Derived Therapies for Parkinson’s Disease: From Cell Assessment and Imaging Modalities to Clinical Trials

et al. 2020

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Curative therapies or treatments reversing the progression of Parkinson's disease (PD) have attracted considerable interest in the last few decades. PD is characterized by the gradual loss of dopaminergic (DA) neurons and decreased striatal dopamine levels. Current challenges include optimizing neuroprotective strategies, developing personalized drug therapy, and minimizing side effects from the long-term prescription of pharmacological drugs used to relieve short-term motor symptoms. Transplantation of DA cells into PD patients' brains to replace degenerated DA has the potential to change the treatment paradigm. Herein, we provide updates on current progress in stem cell-derived DA neuron transplantation as a therapeutic alternative for PD. We briefly highlight cell sources for transplantation and focus on cell assessment methods such as identification of genetic markers, single-cell sequencing, and imaging modalities used to access cell survival and function. More importantly, we summarize clinical reports of patients who have undergone cell-derived transplantation in PD to better perceive lessons that can be drawn from past and present clinical outcomes. Modifying factors include (1) source of the stem cells, (2) quality of the stem cells, (3) age of the patient, (4) stage of disease progression at the time of cell therapy, (5) surgical technique/practices, and (6) the use of immunosuppression. We await the outcomes of joint efforts in clinical trials around the world such as NYSTEM and CiRA to further guide us in the selection of the most suitable parameters for cell-based neurotransplantation in PD.

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Reduced Nurrl Expression Increases the Vulnerability of Mesencephalic Dopamine Neurons to MPTP‐Induced Injury

Cited by 155 publications

References 24 publications

Nur transcription factors in stress and addiction

Nur transcription factors in stress and addiction

MK-801 (Dizocilpine) Regulates Multiple Steps of Adult Hippocampal Neurogenesis and Alters Psychological Symptoms via Wnt/β-Catenin Signaling in Parkinsonian Rats

Current Status of Stem Cell-Derived Therapies for Parkinson’s Disease: From Cell Assessment and Imaging Modalities to Clinical Trials

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