PhD Scientific Days 2022

Theoretical Medicine (Poster discussion will take place on the terrace of the room during the Coffee Break)

Neuroprotective effect of the N,N-Dimethyltryptamine

Text of the abstract

Introduction

N,N-Dimethyltryptamine (DMT) is a natural hallucinogen, the active component of the ayahuasca brew used as a spiritual medicine by indigenous people in the Amazonian basin. DMT is synthetized in the human body under normal circumstances and under pathological conditions as well, although it’s function and it’s mechanism of action is poorly understood. It was proven in earlier studies that DMT has a highly beneficial effect on cell survival under ischemic conditions. This effect is at least partly mediated by the sigma-1 receptor.

Aims

Purpose of our experiment was to test the neuroprotective potential of the DMT under ischemia-reperfusion conditions in a rat middle cerebral artery stroke model.

Method

We used a transient middle cerebral artery occlusion model. The ischemic period lasted for 1 hour, followed by 24 hours of reperfusion. The occlusion was proved by laser Doppler imaging. Osmotic pumps were implanted in the abdominal cavity of the animals at the beginning of the reperfusion period to provide 24 hours of balanced DMT and sigma receptor antagonist absorption. 24 hours later magnetic resonance imaging was performed, then serum and brain specimens were collected for immunohistology, ELISA and QPCR.

The second part of the experiment investigated 30 days of reperfusion after 1 hour of ischemia, which allowed us to test the long term effects of the DMT administered in the first 24 hours of stroke. The animals were tested in a rodent staircase, standardly used to assess the limb motor function and regeneration after stroke.

Results

The DMT-treated group showed smaller infarct laesion volumes, maintained blood-brain barrier function via smaller inflammatory response and apoptosis, an increased regenerative response and better functional outcome at 30 days.

Conclusion

Given the clinically relevant timing of administration, the endogenous nature and high affinity of DMT to the human brain, DMT may have an important future implication for stroke therapy.

Funding

SUPPORTED BY THE ÚNKP-21-3 NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR INNOVATION AND TECHNOLOGY FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND.