OPEN Foundation

Day: 14 March 2017

Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis

Abstract

Type A monoamine oxidase (MAOA) catabolizes monoamine transmitters, serotonin, norepinephrine and dopamine, and plays a major role in the onset, progression and therapy of neuropsychiatric disorders. In depressive disorders, increase in MAOA expression and decrease in brain levels of serotonin and norepinephrine are proposed as the major pathogenic factors. The functional polymorphism of MAOA gene and genes in serotonin signal pathway are associated with depression. This review presents recent advance in studies on the role of MAOA in major depressive disorder and related emotional disorders. MAOA and serotonin regulate the prenatal development and postnatal maintenance of brain architecture and neurocircuit, as shown by MAOA-deficient humans and MAO knockout animal models. Impaired neurogenesis in the mature hippocampus has been proposed as “adult neurogenesis” hypothesis of depression. MAOA modulates the sensitivity to stress in the stages of brain development and maturation, and the interaction of gene–environmental factors in the early stage regulates the onset of depressive behaviors in adulthood. Vice versa environmental factors affect MAOAexpression by epigenetic regulation. MAO inhibitors not only restore compromised neurotransmitters, but also protect neurons from cell death in depression through induction of anti-apoptotic Bcl-2 and prosurvival neurotrophic factors, especially brain-derived neurotrophic factor, the deficiency of which is detected in depression. This review discusses novel role of MAOA and serotonin in the pathogenesis and therapy of depressive disorders.

Naoi, M., Maruyama, W., & Shamoto-Nagai, M. (2017). Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis. Journal of Neural Transmission, 1-14. 10.1007/s0070
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Is Ayahuasca a Potential Ethnic Plant for the Treatment of Parkinson’s Disease?

Abstract

Objective: Investigate the MAO inhibitory properties, toxicity, behavioral and neuroprotective properties of ayahuasca in mice and dopamine rich neuroblastoma cells in order to assess its potential effects on PD. 

Methods: This study examined the effects of the soluble extract of Banisteriopsis caapi on the activity MAO in mouse brain, the MAO inhibitory activity using HPLC with electrochemical detection and the animal´s behavior in an open field and marble burying test. In vitro cell-based assays in neuroblastoma NB69 cells were employed for evaluation of the antioxidant property of ayahuasca by measuring the auto-oxidation to quinones upon dopamine exposure and its neuroprotective effects against cytotoxicity induced by DA and rotenone. The neuroprotective activity was determined by MTT, LDH and trypan blue or propidium iodide (PI) staining. 

Results: Intraperitoneal injection in mice of ayahuasca extract produced a significant striatal inhibitory effect on MAO A and MAO B activity. In mice striatum of ayahuasca treated mice there is an elevation of dopamine and reduction of the levels of di-hydroxy-phenyl acetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-indole acetic acid (5-HIAA). After ayahuasca administration, the mice display less anxiogenic behavior in marble burying test and less exploratory activities in the open field tests. Results demonstrated no significant antioxidative and neuroprotective effects of ayahuasca on dopamine and rotenone toxicity. 

Conclusion: Ayahuasca extract due its strong inhibitory effect on MAO A activity and more powerful inhibition of MAO B, and absence of toxicity could be used as an alternative or complementary therapy for the treatment of Parkinson´s disease.

Perucho, J., Alarcón, F., Mena, M. Á., de Yebenes, J. G., & Casarejos, M. J. Is Ayahuasca a Potential Ethnic Plant for the Treatment of Parkinson’s Disease?.
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30 April - Q&A with Rick Strassman

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