Benneth Ben-Azu - Mindscape Collective

The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics.

Neurochemical research April 1, 2023 Jared VanderZwaag, Torin Halvorson, Kira Dolhan et al. 25 citations

Microglia, the brain's resident immune cells, are emerging as a key target for new psychiatric drugs. This review examines how psychedelics (psilocybin, LSD), ketamine, and propofol interact with microglia to produce therapeutic effects. The authors detail pathways including sigma-1 receptors, serotonin and GABA signaling, and tryptophan metabolism through which these agents modulate microglial activity and inflammation, likely contributing to their benefits in mood disorders and addiction. The paper also discusses future directions, including implications for aging, glial cell heterogeneity, and advanced research methods.

DOI: 10.1007/s11064-022-03772-0 Full text Depression Ketamine Neuroplasticity Anesthetics +6

Effective action of silymarin against ketamine-induced schizophrenia in male mice: Insight into the biochemical and molecular mechanisms of action.

Journal of psychiatric research November 1, 2024 Benneth Ben-Azu, Aliance R Fokoua, Olajide S Annafi et al. 24 citations

Silymarin, a polyphenolic flavonoid with neuroprotective functions, prevented and reversed schizophrenia-like behaviors in mice given ketamine, an NMDA antagonist that induces neurochemical dysregulation, neuroimmune stress, and oxidative stress. In a preventive-reversal model, silymarin (50 and 100 mg/kg) reduced ketamine-induced increases in dopamine, serotonin, acetylcholinesterase, malondialdehyde, and nitrite in the striatum, prefrontal cortex, and hippocampus. It improved hyperlocomotion, stereotypy, memory, and social impairments without causing catalepsy. Silymarin also lowered inflammatory markers (myeloperoxidase, tumor-necrosis factor-α, interleukin-6) and normalized decreased brain-derived neurotrophic factor, glutathione, catalase, and superoxide-dismutase levels. The antipsychotic effect may involve normalization of neurochemical and neurotrophic changes.

DOI: 10.1016/j.jpsychires.2024.09.003 Full text Antipsychotics Negative symptoms Neuropharmacology Psychosis +6

Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology July 3, 2025 Christian I Uruaka, Benneth Ben-Azu, Noah A Omeiza et al. 6 citations

Geraniol, a natural compound, prevented and reversed schizophrenia-like behaviors—hyperactivity, impaired spatial memory, and social withdrawal—induced by ketamine in male Swiss mice. It restored antioxidant defenses (glutathione, superoxide dismutase, catalase), reduced oxidative damage (malondialdehyde, nitrite), and lowered inflammatory cytokines (TNF-α, IL-6) in the striatum, prefrontal cortex, and hippocampus. Geraniol also suppressed expression of NF-κB, COX-2, and iNOS proteins in those brain regions. The findings suggest geraniol has neuroprotective and neurorestorative effects against schizophrenia-like symptoms by counteracting oxidative stress and neuroinflammation.

DOI: 10.1007/s11481-025-10226-1 Full text Anti-inflammation Antioxidant Geraniol Neuroinflammation +1

Papers

The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics.

Effective action of silymarin against ketamine-induced schizophrenia in male mice: Insight into the biochemical and molecular mechanisms of action.

Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.