Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation

Chung, Young Cheul; Kim, Sang R.; Park, Ju Young; Chung, Eun‐Sung; Park, Keun W.; Won, So Yoon; Bok, Eugene; Jin, Minyoung; Park, Eun Su; Yoon, Sung Hwa; Ko, Hyuk Wan; Kim, Yoon Seong; Jin, Byung Kwan

doi:10.1016/j.neuropharm.2011.01.043

Cited by 115 publications

(129 citation statements)

References 58 publications

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“…Although the specific cause of PD is yet to be established, a growing body of evidence supports the theory that microglial activation-derived oxidative stress increases the risk of PD (3). In the substantia nigra (SN) of PD patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD, key enzymes involved in reactive oxygen species (ROS) production, such as microglial NAPDH oxidase, are upregulated in damaged areas and contribute to DA neuronal death (4)(5)(6)(7). In addition, proinflammatory cytokines, such as IL-1b and TNF-a, are augmented in PD patients (8,9) and participate in DA neuronal death in the MPTP model of PD (10,11).…”

Section: P Arkinson's Disease (Pd) Is a Common Neurodegenerativementioning

confidence: 99%

“…Brains were dissected from the skull, postfixed overnight in buffered 4% paraformaldehyde at 4˚C, stored in 30% sucrose solution at 4˚C until they sank, and freeze-sectioned with a sliding microtome into 30-mm-thick coronal sections. All sections were collected in six separate series and processed for immunostaining, as described previously (4,5). In brief, brain sections were rinsed in PBS and incubated overnight at room temperature (RT) with primary Abs, specifically anti-macrophage Ag complex-1 (MAC-1; 1:200 dilution; Serotec, Oxford, U.K.) for microglia and anti-tyrosine hydroxylase (TH; 1:2000 dilution; Pel-Freez Biologicals, Rogers, AR) for DA neurons.…”

Section: Tissue Preparation and Immunostainingmentioning

confidence: 99%

“…The total number of TH-positive neurons was counted in the various animal groups at 7 d postinjection (MPTP or saline) using the optical fractionator method performed on an Olympus Computer Assisted Stereological Toolbox system version 2.1.4 (Olympus Denmark, Ballerup, Denmark) as previously described (4,5). Actual counting was performed using a 1003 oil objective.…”

Section: Stereological Cell Countsmentioning

confidence: 99%

“…As previously described (4,5), the OD of TH-positive fiber in striatum (STR) was examined at 35 original magnification using the IMAGE PRO PLUS system (Version 4.0; Media Cybernetics, Silver Spring, MD) on a computer attached to a light microscope (Zeiss Axioskop, Oberkochen, Germany) interfaced with a CCD video camera (Kodak Mega Plus model 1.4 I; Kodak, New York, NY). To control variations in background illumination, the average of background density readings from the corpus callosum was subtracted from that of density readings of the STR for each section.…”

Section: Densitometric Analysismentioning

confidence: 99%

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Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

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111

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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Section: P Arkinson's Disease (Pd) Is a Common Neurodegenerativementioning

confidence: 99%

Section: Tissue Preparation and Immunostainingmentioning

confidence: 99%

Section: Stereological Cell Countsmentioning

confidence: 99%

Section: Densitometric Analysismentioning

confidence: 99%

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Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

Self Cite

111

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“…Fluoxetine, paroxetine, and sertraline were all found to have this effect in animals [293][294][295][296][297][298][299][300]. In contrast to these findings, mRNA expression of TNF-α, IL-1α, IL-1β, and intercellular adhesion molecule-1 (ICAM-1) was increased in vivo using polymerase chain reaction (PCR) analysis and may affect the BBB permeability [14].…”

Section: Antidepressants Affect the Neuroinflammatory Environmentmentioning

confidence: 94%

Antidepressant use and risk of central nervous system metastasis

et al. 2016

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Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson's disease

et al. 2012

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This study examined whether antidepressants delay the need for dopaminergic therapy or change the degree of motor impairment and disability in a population of early Parkinson's disease (PD) patients. Preclinical studies have indicated that antidepressants modulate signaling pathways involved in cell survival and plasticity, suggesting they may serve to both treat PD-associated depression and slow disease progression. A patient-level meta-analysis included 2064 patients from the treatment and placebo arms of the following trials: FS1, FS-TOO, ELLDOPA, QE2, TEMPO, and PRECEPT. Depression severity was determined at baseline, and antidepressant use was reported in a medication log each visit. Kaplan-Meier curves and time-dependent Cox proportional hazards models determined associations between depression severity and antidepressant use with the primary outcome, time to initiation of dopaminergic therapy. ANCOVAs determined associations with the secondary outcome, degree of motor impairment and disability, reported as annualized change in UPDRS scores from baseline to final visit. When controlling for baseline depression, the initiation of dopaminergic therapy was delayed for subjects taking tricyclic antidepressants compared with those not taking antidepressants. No significant differences were found in UPDRS scores for subjects taking antidepressants compared with those not taking antidepressants. Tricyclic antidepressants are associated with a delay in reaching the end point of need to start dopaminergic therapy. The lack of change in overall UPDRS scores suggests the delay was not attributable to symptomatic effects.

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Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation

Cited by 115 publications

References 58 publications

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Antidepressant use and risk of central nervous system metastasis

Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson's disease

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