Molecular neurobiology
May 1, 2025
Rick Wilhiam de Camargo, Larissa Joaquim, Richard Simon Machado et al.
13 citations
Pretreatment with the psychoactive decoction Ayahuasca (AYA) for three days before inducing sepsis in rats reduced anxiety-like behaviors and neuroinflammation. AYA increased time spent in the open arms of an elevated plus maze and prevented excessive grooming and rearing, indicating anxiolytic effects. It raised levels of the anti-inflammatory cytokine interleukin-4 in the prefrontal cortex and cortex and brain-derived neurotrophic factor in the cortex. AYA also increased myeloperoxidase activity in the prefrontal cortex and hippocampus while decreasing nitrite/nitrate concentrations across multiple brain regions, suggesting enhanced neutrophil activation and reduced nitric oxide signaling. Additionally, AYA prevented lipid peroxidation in the prefrontal cortex, hippocampus, and cortex. These findings suggest AYA may protect against sepsis-induced neuroinflammation, oxidative stress, and anxiety-like symptoms.
Molecular neurobiology
November 1, 2024
Adam Lee, Paul Thuras, Joshua Baller et al.
9 citations
Meditation-based therapies such as mindfulness-based stress reduction and Transcendental Meditation can reduce PTSD symptoms in veterans. In 72 veterans with PTSD, those with the 5HTTLPR LALA high expression genotype of the serotonin transporter gene who had experienced early life trauma showed greater symptom improvement. Additionally, changes in DNA methylation at nine specific sites in the FKBP5 gene from before to after treatment were linked to greater symptom improvement, with an odds ratio of 2.8. These findings suggest that genetic and epigenetic markers in the SLC6A4 and FKBP5 genes may be important for understanding treatment mechanisms and predicting symptom improvement.
Molecular neurobiology
September 1, 2024
Jennifer A Cale, Ethan J Chauhan, Joshua J Cleaver et al.
8 citations
Rats exposed to both neonatal PCP and post-weaning isolation (dual-hit) showed reduced parvalbumin, a marker of GABAergic interneurons, in multiple frontal cortical regions, while isolation-only rats showed reductions only in prelimbic/infralimbic cortex. The dual-hit rats also had increased microglial activation in medial/ventral orbitofrontal cortex and elevated IL-6 in frontal cortex, changes not seen with isolation alone. These neurochemical deficits—involving GABA and inflammation—parallel those in schizophrenia, supporting the dual-hit model's use for testing therapies targeting excitatory-inhibitory imbalance or neuroinflammation.
Molecular neurobiology
June 4, 2025
Naser-Aldin Lashgari, Mahla Khalaji, Pouria Rana et al.
7 citations
Psychedelic compounds such as LSD, psilocybin, MDMA, DMT, and ketamine show therapeutic potential for neurological and psychiatric disorders including depression, PTSD, Alzheimer's disease, and Parkinson's disease. Their benefits arise from multiple mechanisms: anti-inflammatory effects (reducing cytokines like IL-6 and TNF-α), antioxidant activity (inducing SOD), and enhancing neuroplasticity via increased BDNF expression. They also modulate serotonin and dopamine systems. Compared to conventional treatments, psychedelics offer faster onset, longer-lasting effects, and possible disease-modifying properties, making them promising candidates for future therapies.
Molecular neurobiology
February 1, 2025
Na Hu, Yujie Zheng, Xueru Liu et al.
7 citations
Circular RNAs (circRNAs) are abundant in the central nervous system and linked to depression. In a mouse model of depression (chronic unpredictable mild stress), a single intravenous dose of esketamine (5 mg/kg) reduced the expression of circKat6b in hippocampal astrocytes. Overexpressing circKat6b in the hippocampus weakened esketamine's antidepressant effects. Molecular analyses revealed that circKat6b overexpression increased stat1 and p-stat1 expression in astrocytes, and reversed esketamine's suppression of p-stat1. The findings suggest esketamine's antidepressant action may involve lowering circKat6b in hippocampal astrocytes.
Molecular neurobiology
February 5, 2026
Zofia Winczewska, Wiesław J Cubała, Piotr Radziwiłłowicz et al.
5 citations
Oxidative stress (OS) is increasingly recognized not only as a factor in depressive disorders but also as a potential biomarker for the severity and persistence of treatment-resistant depression (TRD). This review synthesizes current evidence linking OS to TRD's chronicity and symptom persistence, suggesting that OS severity may indicate treatment resistance. The authors discuss fast-acting antidepressants and a non-pharmacological nutraceutical approach aimed at reducing OS as a way to fill a therapeutic gap and improve recovery chances. An integrated strategy to lower OS may help overcome treatment resistance in severe TRD, modifying disease course and improving prognosis.
Molecular neurobiology
June 5, 2025
Lucas Santos, Fernanda Dos Santos Petry, Carolina Saibro-Girardi et al.
4 citations
Cortisol, a stress hormone, damages neural-like cells by reducing their survival, increasing inflammatory gene activity (NF-κB and NLRP3), boosting production of reactive oxygen species, and impairing neuroplasticity—lowering BDNF expression and reducing neurite growth and neural connections. Ketamine prevented, attenuated, and reversed these cortisol-induced effects: it reduced inflammation and reactive species, increased BDNF expression, and promoted neurite growth and connectivity. Using an in vitro model, the work demonstrates that ketamine's mechanism of action includes reducing neuroinflammation and enhancing neuroplasticity, beyond its known NMDA receptor antagonism.
Molecular neurobiology
May 23, 2025
Hui Bai, Shan Du, Di Qiu et al.
4 citations
Repeated or prolonged ketamine exposure can damage the developing hippocampus and impair cognitive function. This study in rats and cell lines shows that the enzyme GPX4 protects against this damage. Inhibiting GPX4 with RSL3 worsened lipid peroxidation, mitochondrial damage, and cell death via the NLRP3/caspase-1 pathway, leading to greater hippocampal injury and cognitive deficits. The antioxidant N-acetylcysteine (NAC) reversed these effects. The findings suggest that GPX4 normally suppresses pyroptosis, and boosting its expression may be a strategy to prevent ketamine-induced neurotoxicity in the developing brain.
Molecular neurobiology
March 20, 2025
Hui Bai, Hui Chen, Shan Du et al.
4 citations
Ketamine, a common anesthetic for children, can harm the developing brain by triggering two forms of cell death: ferroptosis and pyroptosis. In experiments on newborn rats and cultured nerve cells, giving N-acetylcysteine (NAC) beforehand reduced damage. NAC lowered harmful lipid oxidation and mitochondrial injury, blocked pyroptosis driven by the NLRP3/caspase-1 pathway, and lessened hippocampal tissue damage and later cognitive problems. The results indicate that reactive oxygen species (ROS) are central to ketamine's developmental neurotoxicity, and NAC protects the brain by inhibiting ROS-driven ferroptosis and pyroptosis.
Molecular neurobiology
February 24, 2025
Zhe Du, Xiu-Mei Zhu, Peng Lv et al.
2 citations
Blocking dopamine D1 receptor (Drd1) activity with an antagonist reduced ketamine-induced schizophrenia-like behaviors in mice, while activating Drd1 with an agonist partly reproduced those symptoms. Transcriptome analysis of the mouse hippocampus identified changes in genes involved in the GTPase activation pathway, including Rgs4 and Gnai3. Two weeks after ketamine administration, Gnai3 mRNA expression decreased in peripheral blood and serum levels of eotaxin-2 increased. These molecular changes suggest Gnai3 and eotaxin-2 may serve as potential peripheral biomarkers for ketamine abuse. The findings demonstrate Drd1 activity's crucial role in ketamine-induced psychotic-like disorder in a mouse model.