General anesthesia is widely used in clinical practice,whereas the exact mechanism behind the general anesthetic-induced reversible loss of consciousness remains unclear.Recent studies have revealed a close relationship between the dopaminergic system and general anesthetic-induced loss of consciousness.This system,encompassing dopamine neurons,dopamine receptors,and related neural pathways,regulates functions such as movement,memory,arousal,and cognition.The dopaminergic neurons in the ventral periaqueductal gray and ventral tegmental area,along with D1 receptors,have been shown to facilitate emergence from anesthesia.However,the role of D2 receptors remains controversial.This review summarizes recent advancements in the role of the dopaminergic system in general anesthesia and the underlying mechanism,with the aim of clarifying the mechanism of general anesthesia and providing a theoretical basis for preventing delayed emergence from anesthesia.
Humans ; Anesthesia, General ; Brain/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine/physiology* ; Animals

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

The distribution of the common acupoints of acupuncture-moxibustion for gastrointestinal diseases conforms to the rule of the segmental homology of somatic afferent nerve-visceral nerve circuit at the spinal cord level. Acupuncture-moxibustion regulates the gastrointestinal function through the nerve-endocrine-immune system, and especially depending on the integrity of the structure and function of nervous system. The somatic afferent nerve-visceral nerve circuit plays an important role in the process of acupuncture and moxibustion for regulating the gastrointestinal function. There are three dimensions. ① The somatic afferent nerve-visceral nerve circuit at the peripheral level, including the somatic afferent nerve-visceral afferent nerve circuit centered on the dorsal root ganglion, and the somatic afferent nerve-visceral efferent nerve circuit centered on the sympathetic ganglia; ② that at the spinal cord level; ③ that at the supra-spinal cord level, focusing on the various reflex circuits with the solitary nucleus involved. The somatic afferent nerve-visceral nerve circuit at the spinal level and inferior to it determines the segmental regulation of acupuncture-moxibustion in the gastrointestinal system, while that at the level superior to the spinal cord determines the supersegmental action of acupuncture-moxibustion in regulating the gastrointestinal system. The neurophysiological mechanism of acupuncture-moxibustion is multi-circuits and multi-targets in regulating gastrointestinal function.
Humans ; Moxibustion ; Acupuncture Therapy ; Acupuncture Points ; Gastrointestinal Tract/physiology* ; Animals ; Neurons, Afferent/physiology* ; Afferent Pathways/physiology*

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

Currently, the incidence of Parkinson's disease (PD) is on the rise. More and more evidences suggest that mitochondrial dysfunction plays a crucial role in the etiology of PD, and dysfunction of mitochondrial complex I (MCI) is one of the most critical factors leading to mitochondrial dysfunction. On one hand, MCI dysfunction stimulates dopaminergic neurons to produce reactive oxygen species (ROS). On the other hand, MCI dysfunction decreases dopaminergic neuron viability and reduces ATP production. All these outcomes promote the pathological progression of PD. This review summarizes research progress on the role of MCI in the pathogenesis of PD, as well as PD treatment strategies based on MCI.
Parkinson Disease/metabolism* ; Humans ; Electron Transport Complex I/metabolism* ; Mitochondria/physiology* ; Reactive Oxygen Species/metabolism* ; Dopaminergic Neurons/metabolism* ; Animals ; Adenosine Triphosphate/metabolism*

The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans ; Dopamine/metabolism* ; Nervous System Diseases/physiopathology* ; Parkinson Disease/physiopathology* ; Receptors, Dopamine/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Alzheimer Disease/physiopathology* ; Schizophrenia/physiopathology* ; Animals

Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopaminergic neurons in the midbrain substantia nigra. This study aimed to investigate the effects of exercise preconditioning on motor deficits and mitochondrial function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sedentary + saline (SS), sedentary + MPTP (SM), exercise + saline (ES), and exercise + MPTP (EM) groups. Mice in the ES and EM groups received 4 weeks of treadmill training, and then SM and EM groups were treated with MPTP for 5 days. Motor function was assessed by behavioral tests, and morphological and functional changes in dopaminergic neurons and mitochondria in the substantia nigra of the midbrain were evaluated using immunohistochemistry, Western blot, and transmission electron microscopy technology. The results showed that, compared with the SM group, the EM group exhibited significantly improved motor ability, up-regulated protein expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the midbrain, and down-regulated protein expression of α-synuclein (α-Syn) in the mitochondria of substantia nigra. Compared with the SM group, the EM group showed up-regulated protein expression levels of mitochondrial fusion proteins, including optical atrophy protein 1 (OPA1) and mitofusin 2 (MFN2), and biogenesis-related proteins, including peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), while the protein expression levels of dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1) were significantly down-regulated. Compared with the SM group, the EM group showed significantly reduced damage to substantia nigra mitochondria, restored mitochondrial membrane potential and ATP production, and decreased levels of reactive oxygen species (ROS). These results suggest that 4-week treadmill pre-training can alleviate MPTP-induced motor impairments in PD mice by improving mitochondrial function, providing a theoretical basis for early exercise-based prevention of PD.
Animals ; Male ; Physical Conditioning, Animal/physiology* ; Mice ; Mice, Inbred C57BL ; Mitochondria/physiology* ; Dopaminergic Neurons ; MPTP Poisoning/physiopathology* ; Substantia Nigra ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Circadian rhythms are core regulatory mechanisms that evolved to align biological functions with the Earth's rotation. These rhythms are conserved across organisms from unicellular life to multicellular species and play essential roles in metabolism, immune responses, and sleep-wake cycle. Circadian disruptions are strongly associated with various diseases. Over the past decades, genetic studies in Drosophila and mice have identified key conserved clock genes and uncovered transcription-translation feedback loops governing circadian regulation. Additionally, rhythmic neurons in the brain integrate complex neural circuits to precisely regulate physiological and behavioral rhythms. This review highlights recent advances in understanding the neuronal circuit mechanisms of rhythmic neurons in the Drosophila brain and discusses future directions for translating circadian rhythm research into chronomedicine and precision therapies.
Animals ; Circadian Rhythm/genetics* ; Neurons/physiology* ; Drosophila/physiology* ; Brain/physiology* ; Nerve Net/physiology*

The purpose of this study was to investigate the anxiety-like behaviors, circadian rhythms and sleep, and to elucidate the possible underlying mechanisms of the abnormal sleep behavior in Shank3 gene knockout (Shank3-KO) mice. The anxiety-like behaviors were detected by elevated plus-maze (EPM) test, open field test (OFT) and tail suspension test (TST). The circadian rhythms were detected by running wheel test. The electroencephalogram (EEG)/electromyogram (EMG) recordings were performed synchronically by polysomnograph. The distribution of SHANK3 in anterior cingulate cortex (ACC), paraventricular thalamus (PVT), nucleus accumbens (NAc), basolateral amygdala (BLA) and hippocampal CA2 region in wild type (WT) mice was detected by immunofluorescence assay. The protein expression of c-Fos in PVT, ACC and NAc was also detected by immunofluorescence assay during light cycle. The colocalization of c-Fos and vesicular glutamate transporter 2 (Vglut2, a marker for glutamatergic neurons) in the PVT was detected by immunofluorescence double labeling experiment. The results of EPM test showed that, compared with the WT mice, the Shank3-KO mice showed less time in open arms and less number of open arm entries. The results of OFT showed that the Shank3-KO mice showed less time in central area and less number of central area entries. The immobility time of Shank3-KO mice was increased in the TST. The results of running wheel rhythm test showed that the phase shift time of Shank3-KO mice in the continuous dark period was increased. The results of EEG/EMG recording showed that, compared with the WT mice, the duration of wakefulness in Shank3-KO mice was increased and the duration of non-rapid eye movement (NREM) sleep was decreased during light phase; The bout number of wakefulness was increased, the bout number of NREM sleep was decreased, NREM-wake transitions were increased, and wake-NREM transitions were decreased during light phase. SHANK3 was expressed in ACC, PVT, NAc and BLA in the WT mice. The expression of c-Fos in the PVT of Shank3-KO mice was up-regulated 2 h after entering the light phase, and majority of c-Fos was co-localized with Vglut2. These results suggest that the anxiety level of Shank3-KO mice is increased, the regulation of the internal rhythms is decreased, and the bout number of wakefulness is increased during light phase. The glutamatergic neurons in PVT may be involved in the regulation of abnormal sleep behavior in Shank3-KO mice during the light phase.
Animals ; Mice, Knockout ; Mice ; Neurons/metabolism* ; Nerve Tissue Proteins/physiology* ; Male ; Midline Thalamic Nuclei/cytology* ; Circadian Rhythm/physiology* ; Sleep/physiology* ; Anxiety/physiopathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Vesicular Glutamate Transport Protein 2/metabolism* ; Mice, Inbred C57BL ; Microfilament Proteins

As an important part of the cytoskeleton, microtubules play a crucial role in many cellular processes, such as cell division, intracellular transport, and maintaining cell morphology. The MAP1 family is an important family of microtubule-associated proteins, which includes three members: MAP1A, MAP1B, and MAP1S. These proteins are widely involved in the dynamic regulation of the cytoskeleton and play a key role in the development and function of the central nervous system, especially in the development and function of neurons. This study reviews the research progress of the MAP1 family, mainly focusing on the structure and function of MAP1 family members, and paying particular attention to their roles in neuronal development and regeneration, regulatory mechanisms, and neurodegenerative diseases.
Humans ; Animals ; Microtubule-Associated Proteins/classification* ; Neurons/cytology* ; Neurodegenerative Diseases/physiopathology* ; Microtubules/physiology* ; Cytoskeleton/physiology*