Differentiation of mouse Neuro 2A cells into dopamine neurons

Tremblay, Roger; Sikorska, Marianna; Sandhu, Jagdeep K.; Lanthier, Patricia; Ribecco-Lutkiewicz, Maria; Bani‐Yaghoub, Mahmud

doi:10.1016/j.jneumeth.2009.11.004

Cited by 236 publications

(195 citation statements)

References 35 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…We first examined for the protein level of MAOB as it relates to Sig-1Rs. To this end, we used the method that causes the differentiation of Neuro2A cells into dopaminergic cells expressing MAOB (32) (Fig. 4A).…”

Section: Sig-1r Apparently Interacts Specifically With a Ne Integral mentioning

confidence: 99%

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

Tsai

Chuang

Tsai

et al. 2015

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

115

View full text Add to dashboard Cite

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.T he endoplasmic reticulum (ER) plays important roles in cellular functions, including synthesis of proteins and regulation of Ca 2+ signaling between the ER and plasma membrane (1) and between the ER and mitochondria (2-4). However, because the ER interacts with other organelles in the cell, other functions related to the ER remain to be uncovered.The sigma-1 receptor (Sig-1R) (5-8) is an ER chaperone molecule that resides at the ER-mitochondrion interface referred to as the mitochondria-associated ER membrane (MAM), where the Sig-1R ensures proper ER-mitochondrion Ca 2+ signaling for cellular survival (3, 9), as well as sustains the activity of an ER stress sensor IRE1 at the MAM (10). The Sig-1R can translocate from the MAM to plasma membrane of the cell to regulate ion channels and receptors on the plasma membrane (8,(11)(12)(13)(14). Cocaine is a Sig-1R agonist (3) that causes the dissociation of Sig-1R from its cognate binding partner BiP (3,8), and consequently the translocation of Sig-1Rs to the plasma membrane, where Sig-1Rs interact with voltage-gated potassium channel subfamily A member 2 (Kv1.2) to shape the neuronal and behavioral responses to cocaine (15).Cocaine also causes the translocation of Sig-1Rs from the ER to the nucleus (16), where Sig-1Rs are shown to be present at the nuclear envelope (NE) (17). H...

show abstract

Section: Sig-1r Apparently Interacts Specifically With a Ne Integral mentioning

confidence: 99%

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

Tsai

Chuang

Tsai

et al. 2015

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

115

View full text Add to dashboard Cite

show abstract

“…Mouse N2a neuroblastoma cells can be differentiated into various neuronal types dependent upon the method used (Manabe et al, 2005;Tremblay et al, 2010). For example, serum withdrawal in the presence of retinoic acid induces differentiation into cholinergic neurons, whereas dibutyryl cAMP promotes the development of dopaminergic neurons (Manabe et al, 2005;Tremblay et al, 2010).…”

Section: Characterisation Of Cholinergic Neuronal Phenotype and Tg Exmentioning

confidence: 99%

“…For example, serum withdrawal in the presence of retinoic acid induces differentiation into cholinergic neurons, whereas dibutyryl cAMP promotes the development of dopaminergic neurons (Manabe et al, 2005;Tremblay et al, 2010). In this study N2a cells were induced to differentiate using retinoic acid in order to avoid potential problems using dibutyryl cAMP when assessing functional responses mediated by the Gs-protein coupled PAC1 receptor.…”

Section: Characterisation Of Cholinergic Neuronal Phenotype and Tg Exmentioning

confidence: 99%

Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells

Algarni

Hargreaves

Dickenson

2017

Biochemical Pharmacology

View full text Add to dashboard Cite

“…The homogenized samples were centrifuged at 20,000× g for 10 minutes at 4 ºC and the supernatants were analyzed using reverse-phase C18 HPLC column (4.6 × 150 mm; Synergi 4 μ particle size Hydro-RP 80Å; Phenomenex, Torrance, CA, USA) equipped with a 3 mm C18 Aqua guard cartridge (Phenomenex) as described previously (Tremblay et al, 2010).…”

Section: Measurement Of Dopamine Levelsmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

show abstract

Differentiation of mouse Neuro 2A cells into dopamine neurons

Cited by 236 publications

References 35 publications

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Contact Info

Product

Resources

About