Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic...

Area of Science:

• Neuroscience
• Oncology
• Pharmacology

Background:

• Cancer-related cognitive impairment (CRCI) affects patient quality of life but is often underrecognized.
• CRCI involves anxiety, depression, and memory deficits, linked to neuroinflammation and altered neurochemistry.

Purpose of the Study:

• To investigate tabernanthalog (TBG), a non-hallucinogenic compound, as a potential treatment for CRCI.
• To explore TBG's effects on neuroinflammation and microglial activation in a mouse model of CRCI.

Main Methods:

• Utilized a Lewis lung carcinoma (3LL) mouse model to induce CRCI.
• Conducted behavioral assessments, biochemical analyses, and gene expression studies.
• Investigated TBG's effects in vivo and in vitro on neuroinflammatory markers.

Main Results:

• Tumor-bearing mice exhibited anxiety-like behavior, memory impairment, reduced tryptophan, and altered hippocampal gene expression.
• TBG treatment reversed behavioral deficits and normalized microglial activation and gene expression.
• TBG suppressed neuroinflammatory gene expression in microglial cells in vitro.

Conclusions:

• TBG effectively alleviates CRCI-like symptoms in a preclinical model.
• TBG's therapeutic effects are mediated by the modulation of neuroinflammation and microglial activation.
• TBG represents a promising therapeutic candidate for managing cognitive and emotional dysfunction in cancer patients.