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

Singh, Sonu; Mishra, Akanksha; Srivastava, Neha; Shukla, Shubha

doi:10.1021/acschemneuro.6b00354

Cited by 33 publications

(19 citation statements)

References 76 publications

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“…After intraperitoneal dizocilpine (0.2 mg/kg), rats spent more time in the light chamber ( p < 0.01), and more contact time during the social interaction test ( p < 0.05) in comparison to 6-OHDA lesioned rats. This suggests that MK-801 ameliorates depressive-like behavior in 6-OHDA lesioned rats 54 .…”

Section: Resultsmentioning

confidence: 83%

“…There are reports of neuroprotection after acute dextromethorphan in a number of PD models 52 , 70 . A recent study showed improvement in anxiety and depressive symptoms in a PD rat model with dizocilpine treatment, which was speculated to have occurred via Wnt signaling 54 . In summary, the use of NMDA antagonists is becoming more common in treating psychiatric symptoms, especially depression.…”

Section: Discussionmentioning

confidence: 99%

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NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease

et al. 2018

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Among patients with Parkinson’s disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine. A comprehensive literature search was conducted using the PubMed database. We also searched the following databases up to March 1, 2018: Ovid MEDLINE, PsycINFO, CINAHL, Google Scholar, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The following keywords were used: NMDA antagonist and Parkinson’s disease. Two authors independently reviewed the articles identified from the search using specific selection criteria, focusing on studies of mood, psychiatric condition, depression, cognition, and quality of life, and the consensus was reached on the 20 studies included. There is a preliminary evidence that NMDA antagonists may modulate psychiatric symptoms in PD. However, current evidence of psychiatric symptom-modifying effects is inconclusive and requires that further trials be conducted in PD. The repurposing of old NMDA antagonists, such as ketamine for depression and newer therapies, such as rapastinel, suggests that there is an emerging place for modulating the glutamatergic system for treating non-motor symptoms in PD.

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Section: Resultsmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease

et al. 2018

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“…NMDA activate NMDAR on hippocampal neurons, change synaptic plasticity and release excitatory neurotransmitters that condition and inhibit MK-801 in a non-competitive role to improve cell vitality ( 28 , 29 ). A further study has revealed that MK-801 treatment [0.2 mg/kg, intraperitoneal (IP)] increases NSC proliferation in the hippocampus of a rat model with Parkinson's disease ( 30 ). MK-801 treatment results in enhanced hippocampal neurogenesis in the model.…”

Section: Discussionmentioning

confidence: 99%

Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK‑801

et al. 2018

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The purpose of the present study was to investigate effects of N-methyl-D-aspartate (NMDA) on proliferation and apoptosis of hippocampal neural stem cells (NSCs) treated with dizocilpine (MK-801). Cultures of hippocampal NSCs were randomly divided into four groups consisting of an untreated control, cells treated with MK-801, NMDA and a combination of MK801 and NMDA (M+N). Proliferative and apoptotic responses for each of the experimental groups were determined by MTS and flow cytometry. The results revealed that MK-801 and NMDA exerted significant effects on hippocampal NSCs proliferation. Cell survival rates decreased in MK-801, NMDA and M+N treated groups compared with the control group. Cells survival rates in NMDA and M+N treated groups increased compared with the MK-801 treated group. MK-801 and NMDA were demonstrated to significantly affect apoptosis in hippocampal NSCs. Total and early stages of apoptosis in MK-801 and NMDA groups significantly increased compared with the control group. Total and early apoptosis of NSCs in the M+N group significantly decreased compared with MK-801 and NMDA groups. Late apoptosis of NSCs in MK-801 and NMDA groups significantly decreased compared with the control group. Late apoptosis of NSCs in the M+N group significantly increased compared with MK-801 and NMDA groups. The present study revealed that MK-801 inhibited proliferation and increased apoptosis in hippocampal NSCs. NMDA may reduce the neurotoxicity induced by MK-801, which may be associated with its activity towards NMDA receptors and may describe a novel therapeutic target for the treatment of schizophrenia.

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“… 14 Studies have shown that 6-hydroxydopamine (6-OHDA) induced dopamine depletion in the SN (SNpc) leads to decreased NSC proliferation in SVZ and SGZ in rodents. 15 – 17 In contrast, D2/D3 receptor stimulation did not show any effect on NSC proliferation and DAergic neuronal differentiation in murine and human brain–derived neural progenitor cells (NPCs). 18 Interestingly, a study showed that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)–induced dopamine depletion in the midbrain transiently increased NSC proliferation and postmitotic neuronal differentiation in hippocampal DG in mice.…”

Section: Introductionmentioning

confidence: 99%

Physiological and Functional Basis of Dopamine Receptors and Their Role in Neurogenesis: Possible Implication for Parkinson’s disease

2018

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Dopamine controls various physiological functions in the brain and periphery by acting on its receptors D1, D2, D3, D4, and D5. Dopamine receptors are G protein–coupled receptors involved in the regulation of motor activity and several neurological disorders such as schizophrenia, bipolar disorder, Parkinson’s disease (PD), Alzheimer’s disease, and attention-deficit/hyperactivity disorder. Reduction in dopamine content in the nigrostriatal pathway is associated with the development of PD, along with the degeneration of dopaminergic neurons in the substantia nigra region. Dopamine receptors directly regulate neurotransmission of other neurotransmitters, release of cyclic adenosine monophosphate, cell proliferation, and differentiation. Here, we provide an update on recent knowledge about the signalling mechanism, mode of action, and the evidence for the physiological and functional basis of dopamine receptors. We also highlight the pivotal role of these receptors in the modulation of neurogenesis, a possible therapeutic target that might help to slow down the process of neurodegeneration.

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

Cited by 33 publications

References 76 publications

NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease

NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease

Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK‑801

Physiological and Functional Basis of Dopamine Receptors and Their Role in Neurogenesis: Possible Implication for Parkinson’s disease

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