Nature communications
August 23, 2024
David H Sarrazin, Wilf Gardner, Carole Marchese et al.
41 citations
Depression involves disrupted circadian rhythms, but the role of internal clocks in mood-regulating brain areas was unclear. In a mouse model of depression, the medial prefrontal cortex (mPFC) showed increased expression of circadian negative-loop genes and decreased positive-clock regulators, and the rapid antidepressant ketamine counteracted these changes. Removing the clock gene Bmal1 from excitatory neurons prevented both depression-like behavior and ketamine's effects. Silencing the clock gene Per2 in mPFC produced antidepressant-like effects, while activating REV-ERB worsened depression and blocked ketamine. Boosting the clock activator ROR had antidepressant-like effects, increasing plasticity-related proteins and synaptic receptors in mPFC. The mPFC molecular clock critically regulates depression-like behavior, and targeting it therapeutically may influence glutamatergic plasticity.
bioRxiv Preprint Server
September 19, 2022
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
preprint
Inhaling 50% nitrous oxide (laughing gas) for one hour and a single low dose of ketamine both alter gene expression in the medial prefrontal cortex of adult mice, particularly affecting regulators of MAPK signaling pathways in pyramidal cells. Nitrous oxide produced much broader and more widespread changes in mRNA expression than ketamine. However, unlike ketamine, nitrous oxide did not increase the firing rate of putative pyramidal neurons or boost gamma brain wave activity. The findings suggest that while both substances share some molecular effects, their neural activity patterns differ markedly.
Journal of neurophysiology
May 1, 2025
Petra Valtonen, Stanislav Rozov, Iina Annala et al.
Short-term administration of nitrous oxide (N2O) increases power in the theta frequency range (4-7 Hz) of the electroencephalogram (EEG) after the gas is withdrawn, but does not affect delta frequency (0.5-4 Hz) power. In a study of 14 healthy male participants, those receiving 50% N2O either continuously for 20 minutes or in two 10-minute inhalations showed rapid EEG transitions during gas administration and withdrawal. Power in high-frequency gamma bands increased during N2O, while beta and alpha frequencies decreased. After withdrawal, theta power increased in several electrodes, with negligible differences between the two treatment groups. The effect was reproducible with repeated dosing.
Neuropharmacology
December 15, 2024
Okko Alitalo, Samuel Kohtala, Marko Rosenholm et al.
A brief exposure to nitrous oxide (N2O) causes a drop in body temperature, reduced movement, enhanced slow-wave brain activity, decreased brain glucose use, and increased phosphorylation of TrkB, GSK3β, and p70S6K in the medial prefrontal cortex of adult male mice. Preventing the hypothermic response in a chronic stress model of depression weakened the antidepressant-like behavioral effects of N2O in the saccharin preference test. These findings indicate that N2O treatment modulates TrkB signaling and related neurotrophic pathways in a temperature-dependent manner, linking altered thermoregulation and energy expenditure to antidepressant-like behavioral responses.
European journal of pharmacology
April 5, 2024
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
Inhaling 50% nitrous oxide for one hour and a single low dose of ketamine both alter the activity of genes that regulate mitogen-activated protein kinases in the medial prefrontal cortex of adult mice, particularly in pyramidal cells. Nitrous oxide produced much larger and more widespread changes in gene expression than ketamine. Ketamine increased the firing rate of putative pyramidal neurons and boosted gamma brain wave activity, whereas nitrous oxide did not. The findings suggest that the two drugs share a common molecular target but cause different immediate electrical changes in the brain.