5-MeO-DMT induces NEIL3-independent acute cell proliferation in the adult dentate gyrus
Rafael V Lima Da Cruz, Richardson N. Leão, Thiago C. Moulin
Molecular Brain July 24, 2026 DOI: 10.1186/s13041-026-01337-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult wild-type and Neil3 knockout mice |
| Intervention | 5-MeO-DMT |
| Dose | single dose (not specified) |
| Duration | 12 hours after BrdU administration |
| Topics | 5-MeO-DMT DMT |
| Key findings | 5-MeO-DMT increased acute BrdU labeling in both wild-type and Neil3 knockout mice, with knockout mice showing significantly more BrdU-positive cells than wild-type mice after treatment. NEIL3 is not required for the acute proliferative response. |
Abstract
Abstract Adult dentate gyrus neurogenesis and cell proliferation are regulated by multiple physiological inputs, including experience-dependent signals that have been linked to the DNA glycosylase NEIL3. Whether NEIL3 also gates psychedelic-induced proliferation is unknown. Here we tested the effect of a single dose of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), a serotonergic agonist with psychedelic properties previously shown to increase dentate gyrus neurogenesis, in wild-type and Neil3 knockout adult mice. Mice received intracerebroventricular 5-MeO-DMT or saline, followed by intraperitoneal BrdU injection. Brains were collected 12 h after BrdU administration, and BrdU-positive cells were quantified in horizontal sections of the ventral dentate gyrus. Baseline BrdU labeling did not differ between genotypes, consistent with NEIL3 being dispensable for naïve-state proliferation. 5-MeO-DMT increased acute BrdU labeling in both wild-type and Neil3 knockout mice, with Neil3 knockout mice exhibiting significantly more BrdU-positive cells than wild-type mice after treatment. These results indicate that NEIL3 is may not be required for the acute proliferative response to 5-MeO-DMT and suggest genotype-dependent modulation of this effect.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |