Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors.

The tumor microenvironment (TME) is an innervated and neurochemically active setting. To date, its cholinergic and GABAergic signaling have largely been analyzed as separate systems, contributing to inconsistent findings across the literature. We propose a Calcium-Gated Excitability (CAGE) model, in which α7 nicotinic acetylcholine receptor (nAChR), α4β2 nAChR, GABA type A (GABA_A) and type B (GABA_B) receptors, and α2δ-1 converge on a single downstream variable: Ca²⁺ flux. α7 conducts Ca²⁺ directly; α4β2 may redirect cholinergic input toward GABA release; GABA_A and GABA_B set the direction of the calcium response through intracellular chloride-gradient state and opposing intracellular signaling branches; α2δ-1 sets the gain that determines whether depolarization reaches a functional threshold. The resulting calcium-axis configuration, defined by receptor functional state, chloride-gradient status, α2δ-1 gain, and ligand exposure, shapes Ca²⁺ output and constrains downstream biological responses. Under this framework, some divergent findings on acetylcholine, nicotine, and GABA become testable consequences of distinct calcium-regulatory configurations. CAGE yields testable predictions, including nonlinear nAChR dose–response curves, reversal of GABA_A polarity, α2δ-1-dependent signal scaling, and spatially heterogeneous Ca²⁺ states. Studies evaluating nAChR- and GABA-receptor-targeted therapies without prior calcium-axis stratification may not be underpowered; they may be asking the wrong question.

With the growing use of nanotechnology, the issue of exposure to non-biodegradable nanomaterials is becoming increasingly significant, raising concerns about their potential impact on developing organisms. Their use in dentistry, optoelectronics and biomedicine leads to environmental exposure. Zirconium oxide (ZrO₂) and yttrium oxide (Y₂O₃) nanoparticles are chemically stable and poorly soluble materials; however, their embryotoxicity remains extremely poorly characterised. This study assessed the effect of ZrO₂ and Y₂O₃ nanoparticles on the development of chicken embryos. The nanoparticles were administered into the air chamber of the egg on the first day of incubation at concentrations of 10 and 100 µg/mL. The redox status was assessed based on superoxide dismutase activity, malondialdehyde content and the level of carbonylated proteins. Transcriptomic responses were evaluated using a whole-genome microarray, and selected genes were verified by qPCR. Both types of nanoparticles induced time-dependent changes in markers of oxidative stress. Transcriptomic analysis revealed distinctly different responses, with seven genes showing altered expression following ZrO₂ administration, compared with 555 following Y₂O₃ administration. These results indicate that non-biodegradable metal oxide nanoparticles can influence the redox balance and gene expression during early embryonic development, with the extent of the response depending on the type of nanoparticle.