Proteomic changes induced by harmine in human brain organoids reveal signaling pathways related to neuroprotection
Karina Karmirian, Livia Goto-Silva, Juliana Nascimento, Marcelo N. Costa, José Alexandre Salerno, Isis M. Ornelas, Bart Vanderborght, Daniel Martins-de-Souza, Stevens K. Rehen
bioRxiv (Cold Spring Harbor Laboratory) June 17, 2021 preprint DOI: 10.1101/2021.06.16.448740 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Human brain organoids |
| Intervention | Harmine |
| Duration | 24-hour treatment |
| Topics | Ayahuasca |
| Keywords | Harmine Neuroprotection Creb Signal transduction Cell biology Pi3k/akt/mtor pathway Pharmacology |
| Citations | 1 |
| Key findings | Harmine upregulates proteins involved in synaptic vesicle cycle, cytoskeleton-dependent intracellular transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling, and increases Akt and phosphorylated CREB levels in human brain organoids. |
Abstract
Abstract Harmine is a β-carboline found in Banisteriopsis caapi , a constituent of ayahuasca brew. Ayahuasca is consumed as a beverage in native Americans’ sacred rituals and in religious ceremonies in Brazil. Throughout the years, the beneficial effects of ayahuasca to improve mental health and life quality have been reported, which propelled the investigation of its therapeutic potential to target neurological disorders such as depression and anxiety. Indeed, antidepressant effects of ayahuasca have been described, raising the question of which cellular mechanisms might underlie those effects. Previous animal studies describe potential neuroprotective mechanisms of harmine, including anti-inflammatory and antioxidant activities, and neurotrophin signaling activation. However, the cellular and molecular mechanisms modulated by harmine in human models remain less investigated. Here we analyzed the short-term changes in the proteome of human brain organoids treated with harmine using shotgun mass spectrometry. Harmine upregulates proteins related to synaptic vesicle cycle, cytoskeleton-dependent intracellular transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling pathway. In addition, protein expression levels of Akt and phosphorylated CREB were increased after 24 hour-treatment. Our results shed light on the potential mechanisms that may underlie harmine-induced neuroprotective effects.
Comparable studies
Other experimental studies on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion Human participants (number not stated) | 2011 | Within-subjects experimental study | |
| Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking Participants at spiritual ayahuasca workshops | 2016 | Within-subjects experimental study | n = 26 |
| Metabolism and disposition of N,N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca Healthy male volunteers | 2012 | Observational pharmacokinetic study | n = 10 |
| New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca. | 2018 | Review with original neuroimaging and neurophysiological data | |
| Stability Evaluation of DMT and Harmala Alkaloids in Ayahuasca Tea Samples Ayahuasca tea samples | 2020 | Experimental study |
Citations in the library
Cites 10
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids Pharmacognosy Reviews/Bioinformatics Trends/Pharmacognosy review 2013
- The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Scientific Reports July 7, 2017
- Ayahuasca and the process of regulation in Brazil and internationally: Implications and challenges International Journal of Drug Policy August 19, 2011
and 5 more in the library