1.Effects of electroacupuncture on cognitive impairment and mitophagy mediated by KIF5A/Miro1 pathway in Parkinson's disease mice.
Mengzhu LI ; Jiafan CHEN ; Mengxuan CHEN ; Haiyan LI ; Zhenyi ZHANG ; Da GAO ; Weicong ZENG ; Lijun ZHAO ; Meiling ZHU
Chinese Acupuncture & Moxibustion 2025;45(8):1111-1119
OBJECTIVE:
To explore the improvement effect of electroacupuncture (EA) based on Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) on cognitive impairment in mice with Parkinson's disease (PD), and to explore its regulatory mechanisms on the kinesin family member 5A (KIF5A)/mitochondrial Rho GTPase 1 (Miro1) pathway and mitophagy in prefrontal cortical neurons.
METHODS:
A total of 70 male C57BL/6J mice of clean grade were randomly divided into a normal group (12 mice), a sham operation group (12 mice), and a model pre-screening group (46 mice). Unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle was adopted to establish the PD model in the model pre-screening group. Twenty-four mice after successful modeling were randomly selected and divided into a model group and an EA group, 12 mice in each one. In the EA group, acupuncture was applied at "Shuigou" (GV26) and bilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6), ipsilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6) were connected to EA respectively, with disperse-dense wave, 5 Hz/20 Hz in frequency, 0.5 mA in current intensity, 20 min a time, 6 times a week for 30 days. Cognitive function was assessed by Y-maze and Morris water maze tests; morphology of prefrontal cortex was observed by H.E. staining; reactive oxygen species (ROS) level in prefrontal cortex was detected by fluorescence probe method; mitochondrial morphology and autophagosome ultrastructure were observed by transmission electron microscopy; the mRNA expression of tyrosine hydroxylase (TH) was detected by quantitative real-time PCR; the protein expression of TH, KIF5A, Miro1, p62, Parkin and PTEN induced kinase 1 (PINK1) was detected by Western blot.
RESULTS:
Compared with the sham operation group, both the model group and the EA group exhibited increased rotation number of per minute (P<0.001). Compared with the sham operation group, in the model group, the novel arm exploration time of Y-maze test was shortened (P<0.001), the escape latency of Morris water maze test was prolonged (P<0.05) and the platform crossing number of Morris water maze test was reduced (P<0.01); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was increased (P<0.001), and mitochondrial autophagosomes could be observed; in the prefrontal cortex, the relative expression of ROS was increased (P<0.001), the protein and mRNA expression of TH was decreased (P<0.001), the protein expression of Miro1, PINK1, Parkin was increased (P<0.001, P<0.01), the protein expression of KIF5A and p62 was decreased (P<0.001). Compared with the model group, in the EA group, the novel arm exploration time of Y-maze test was prolonged (P<0.01), the escape latency of Morris water maze test was shortened (P<0.05) and the platform crossing number of Morris water maze test was increased (P<0.05); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was decreased (P<0.001), and the number of mitochondrial autophagosomes reduced and the mitochondrial morphology was improved; in the prefrontal cortex, the relative expression of ROS was decreased (P<0.01), the protein and mRNA expression of TH was increased (P<0.001, P<0.01), the protein expression of Miro1, PINK1, Parkin was decreased (P<0.001, P<0.01, P<0.05), the protein expression of KIF5A and p62 was increased (P<0.01, P<0.05).
CONCLUSION
Xingnao Kaiqiao electroacupuncture effectively alleviates cognitive impairment and damage of neuronal function in PD mice, its mechanism may be related to the regulation of KIF5A/Miro1 pathway, hence reducing the mitophagy in prefrontal cortical neurons.
Animals
;
Electroacupuncture
;
Male
;
Mice
;
Parkinson Disease/physiopathology*
;
Cognitive Dysfunction/psychology*
;
Kinesins/genetics*
;
Humans
;
Mitophagy
;
Mice, Inbred C57BL
;
rho GTP-Binding Proteins/genetics*
;
Mitochondria/genetics*
;
Prefrontal Cortex/metabolism*
2.Neurotoxicity and biomarkers of lead exposure: a review.
Kang-sheng LIU ; Jia-hu HAO ; Yu ZENG ; Fan-chun DAI ; Ping-qing GU
Chinese Medical Sciences Journal 2013;28(3):178-188
Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease
;
chemically induced
;
metabolism
;
pathology
;
physiopathology
;
psychology
;
Animals
;
Behavior
;
drug effects
;
Biomarkers
;
metabolism
;
Brain
;
metabolism
;
pathology
;
physiopathology
;
Brain Diseases
;
chemically induced
;
pathology
;
physiopathology
;
Environmental Exposure
;
adverse effects
;
Humans
;
Lead
;
pharmacokinetics
;
toxicity
;
Lead Poisoning
;
etiology
;
metabolism
;
pathology
;
physiopathology
;
psychology
;
Neurotoxicity Syndromes
;
etiology
;
metabolism
;
pathology
;
physiopathology
;
psychology
;
Parkinson Disease, Secondary
;
chemically induced
;
metabolism
;
pathology
;
physiopathology
;
psychology
;
Schizophrenia
;
chemically induced
;
metabolism
;
pathology
;
physiopathology
3.Relationship between the auditory P300 and the procedural memory function in drug-naive patients with Parkinson's disease.
Gyung Whan KIM ; Young Ho SOHN ; Kyoon HUH ; Jin Soo KIM
Yonsei Medical Journal 1995;36(4):367-371
We evaluated and compared procedural memory and auditory P300 event-related potential in age-matched normal controls (n = 15) and drug-naive patients with Parkinson's disease (n = 16). We used Gollin's incomplete picture test for visual procedural memory function and Tower of Hanoi puzzle for visuomotor procedural memory function. The mean latency of P300 was significantly prolonged in the Parkinsonian group than in the controls. In the neuropsychology test, the patients group revealed selective impairment of visuomotor procedural memory against preserved visual procedural memory. In the patients group, the latency of P300 was inversely correlated with performance of visuomotor procedural memory. These results suggest that prolonged auditory P300 event-related potential show the dysfunction of visuomotor procedural memory in the basal ganglia, which appears to be more selectively impaired than visual procedural memory in drug-naive patients with Parkinson's disease.
*Event-Related Potentials, P300
;
*Evoked Potentials, Auditory
;
Female
;
Human
;
Male
;
Memory/*physiology
;
Middle Age
;
Neuropsychological Tests
;
Parkinson Disease/*physiopathology/*psychology
;
Reaction Time

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