摘要: General anesthesia is widely applied in clinical practice.However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here,we measured the dynamics of five neurotransmitters,including γ-aminobutyric acid, glutamate, norepinephrine,acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

摘要: General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation,axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

摘要: Acetaminophen(APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field(SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

摘要: Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17(PCDH17) is associated with major mood disorders, including bipolar disorder and depression. However, the molecular mechanisms by which PCDH17 regulates spine number,morphology, and behavior remain elusive. In this study, we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons. Selective overexpression of PCDH17in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically, PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin) organization.Specifically, PCDH17 binds to ROCK2, increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3). Inhibition of ROCK2 activity with belumosudil(KD025) ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression, suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development. Hence, these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior, providing pathological insights into the neurobiological basis of mood disorders.

摘要: The Chinese tree shrew(Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans,macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2,CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies.Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

摘要: Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus（lPBN）, composed of external-（elPBN）, dorsal-（dlPBN）, and central/superior-subnuclei（jointly referred to as slPBN）, receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used regionspecific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor（NK1R）(lPBN^NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while el PBN neurons are dispensable for driving such reactions.Notably, lPBN^NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN^NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

摘要: Substance use disorders (SUDs) impact an estimated 300million people worldwide,significantly impairing both health and social functioning.These disorders are marked by an inability to regulate substance use,despite the harmful consequences.Addiction affects various neurotransmitter systems,including dopamine,serotonin,γ-aminobutyric acid(GABA),and glutamate,each of which plays a role in the reward,stress,and self-control pathways of the brain (Koob&Volkow,2016).

摘要: Researchers and clinicians have long been interested in the mechanisms of pain,anesthesia,and addiction.The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage (Raja et al.,2020).

摘要: The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow(Corvus corone), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this,carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria(75.51%) and Firmicutes(22.37%).Significant differences were observed in the relative abundance of Enterococcus faecalis among groups,highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E.faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection.Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha(TNF-α), interferon gamma(IFN-γ), and interleukin 6(IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice,thereby modulating the host's immune regulatory capacity.Therefore, E. faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

摘要: DEAR EDITOR,Big cats, such as Amur tigers (Panthera tigris altaica) and Amur leopards (P. pardus orientalis), are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al., 2022), thus playing a crucial role in maintaining biodiversity and ecosystem integrity by regulating preypredator dynamics. However, human-induced pressures,