Chronic pain, a prevalent chronic disease, frequently manifests not only in physical symptoms but also in cognitive impairment, which seriously affects patients' quality of life. Interneurons are multipolar neurons, most of which are inhibitory, serving as crucial connectors within neural networks. They play key roles in signal transmission and fine-tuning of neural activity. In recent years, growing evidence has shown that interneurons are involved in the development of chronic pain and its associated cognitive dysfunction. Investigating the relationship between interneuron dysfunction and chronic pain-related cognitive impairment is of great significance, offering new potential targets and insights for the development of novel therapeutic approaches.
Interneurons/physiology* ; Humans ; Chronic Pain/complications* ; Cognitive Dysfunction/physiopathology* ; Cognition Disorders/physiopathology* ; Animals

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Cognitive dysfunction often occurs in Alzheimer's disease, Parkinson's disease, cerebrovascular disease, or other neurodegenerative diseases, and can significantly impact the life quality of patients and create serious social, psychological, and economic burdens for individuals and their families. Numerous studies have confirmed that exercise can slow the decline in cognitive function through multiple pathways, in which fibronectin type III domain-containing protein 5 (FNDC5) plays an important role. However, the current research on the modulation of FNDC5 by exercise and its ability to improve hippocampal cognitive function lacks a systematic and comprehensive understanding. Therefore, this review focuses on the latest research progress regarding the role of exercise-induced FNDC5 in cognitive function, systematically reviews the positive effects of FNDC5 on cognitive function impairment caused by various factors, and clarifies the specific mechanisms by which exercise-induced FNDC5 improves cognitive function by inhibiting neuroinflammation and improving hippocampal neurogenesis and hippocampal synaptic plasticity. Based on the existing literature, we also identify the areas that require further research in this field. Overall, this review provides a theoretical basis for exercise-based prevention and improvement of cognitive function impairment.
Humans ; Cognition/physiology* ; Fibronectins/physiology* ; Exercise/physiology* ; Hippocampus/physiology* ; Cognitive Dysfunction/prevention & control* ; Neuronal Plasticity ; Animals ; Neurogenesis

BACKGROUND

Schizophrenia, a common mental disorder, is associated with cognitive impairment in middle-aged and older adults. Research highlights challenges such as white matter loss, dementia risk, psychosocial issues, nursing home admissions, and limited cognitive benefits from antipsychotics. Animal-Assisted Therapy (AAT) is an emerging intervention for mental and physical illnesses, including schizophrenia.

This quasi-experiment included 20 patients from a health care facility, selected through purposive sampling based on inclusion/exclusion criteria.

AAT significantly improved lower body strength (CST) and cognitive abilities (MOCA- P) but had no effect on agility (TUG). Male participants showed greater improvements than females in all domains: CST (+7.8), TUG (-2.365), and MOCA-P (+12). The dropout rate was 50% for females and 20% for males, primarily due to eligibility for discharge.

AAT significantly enhances lower body strength and cognitive function but does not improve agility. It is a safe, feasible adjunct therapy for chronic mental health conditions, though targeted interventions for mobility challenges are needed.

Dementia is an acquired loss of cognitive ability and is found to have a significant physical, psychological, social, and economic impact on patients, families, and communities. Diagnosis of dementia should be based on history and physical examination, together with cognitive, functional, and behavioral assessment. Validated tools such as the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA) should be used to screen for cognitive impairment. Functionality or Activities of Daily Living (ADL) should be assessed using the Katz and Lawton Index. Work-up of patients with dementia includes ruling out dementia-mimicking conditions, including routine hematology (full blood count and ESR), biochemistry (electrolytes, calcium, glucose, renal and liver function), Thyroid function tests, and Serum B12 and folate levels. Neuroimaging is performed to detect reversible causes of cognitive impairment and to determine the subtype of dementia. Family-based and community-based interventions should be offered to patients with dementia.

OBJECTIVE: To investigate the effect of moxibustion on central insulin resistance related proteins of the rats suffering from diabetic cognitive decline, and analyze the underlying mechanism of moxibustion for cognition improvement. METHODS: Using the intraperitoneal injection of STZ combined with a high-fat diet, the rat model of diabetic cognitive decline were prepared. Twenty successfully-modeled rats were assigned randomly into a model group and a moxibustion group, 10 rats in each one. Besides, a blank group was set up with 10 rats collected. In the moxibustion group, suspending moxibustion was applied to "Baihui" (GV20), "Shenting" (GV24) and "Dazhui" (GV14) at the same time, 20 min in each intervention, once a day, and 6 interventions were delivered weekly and the duration of treatment was consecutive 4 weeks. The random blood glucose was measured using glucometer, and the learning-memory ability was detected by water maze test. HE staining was used to observe the morphology of neurons in the hippocampal tissue, real-time PCR assay was to detect mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in the hippocampal tissue. The Western blot method was employed to detect the protein expression of IRS1, PI3K, AKT, phosphorylated IRS1 (p-IRS1), phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in the hippocampal tissue, and the ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT was calculated separately. The immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT was measured using immunofluorescence. RESULTS: Compared with the blank group, the rats of the model group exhibited higher random blood glucose (P<0.001), longer escape latency (P<0.001), severe pathological damage in the hippocampus, lower mRNA expression of IRS1, PI3K, and AKT (P<0.001), reduced ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT (P<0.001), and declined immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT in the hippocampal tissue (P<0.001). In comparison with the model group, for the rats of the moxibustion group, the random blood glucose decreased (P<0.05), the escape latency was shortened (P<0.01), the hippocampal pathological damage was attenuated, the mRNA expression of IRS1, PI3K and AKT increased (P<0.01), the ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT was elevated (P<0.01, P<0.05), and the immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT in the hippocampal tissue was strengthened (P<0.01, P<0.05). CONCLUSION In diabetic rats experiencing cognitive decline, moxibustion can enhance the learning-memory ability, which may be attributed to modulating the protein expression of IRS1, PI3K, and AKT, and their phosphorylation, activating insulin signal transduction, and reducing central insulin resistance.
Animals ; Moxibustion ; Insulin Resistance ; Rats ; Male ; Insulin Receptor Substrate Proteins/genetics* ; Rats, Sprague-Dawley ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Cognitive Dysfunction/genetics* ; Diabetes Mellitus, Experimental/therapy* ; Hippocampus/metabolism* ; Acupuncture Points ; Phosphatidylinositol 3-Kinases/genetics*

The paper introduces the diagnostic and therapeutic ideas and clinical experience of Professor LIU Zhibin in treatment with acupuncture for Parkinson's disease with mild cognitive impairment. Professor LIU believes that the basic pathogenesis of Parkinson's disease with mild cognitive impairment refers to the deficiency of liver and kidney, and the loss of mind control. Therefore, the treatment focuses on nourishing the liver and kidney, regulating the governor vessel, opening the brain orifice, and regulating the mind. The point prescription is composed of Tongdu Tiaoshen zhen (the points for promoting the circulating of the governor vessel and regulating the mind, i.e. four-mind needles [Extra], Shenting [GV24], bilateral Benshen [GB13] and Fengfu [GV16]), xiusanzhen (three-olfaction needles, including bilateral Yingxiang [LI20] and Yintang [GV24⁺]) and zhichan bazhen (eight anti-tremble needles, i.e. Baihui [GV20], Lianquan [CV23], and Hegu [LI4], Waiguan [TE5], Taichong [LR3], Zusanli [ST36], Sanyinjiao [SP6] and Taixi [KI3] on the affected side). Besides, the prescription is modified according to the syndrome, and the special technique of bone-touching needling is combined to enhance the therapeutic effect.
Humans ; Acupuncture Therapy ; Parkinson Disease/psychology* ; Cognitive Dysfunction/complications* ; Male ; Acupuncture Points ; Female ; Aged ; Middle Aged

OBJECTIVE: To observe the clinical efficacy of acupuncture on mild cognitive impairment (MCI) and its effect on gut microbiota. METHODS: A total of 62 MCI patients were randomly divided into an experimental group (31 cases, 2 cases dropped out) and a control group (31 cases). Both groups received exercise and cognitive training. In addition, the experimental group underwent acupuncture treatment at acupoints including Baihui (GV20), Sishencong (EX-HN1), and bilateral Fengchi (GB20), Xuanzhong (GB39), Zusanli (ST36), Yanglao (SI6), Xinshu (BL15), and etc., once every other day, three times per week, for a total of 12 weeks. Before and after treatment, the Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) scores were evaluated in the two groups, changes in gut microbiota were detected using 16S rDNA sequencing technology. The clinical efficacy was assessed after treatment. RESULTS: Compared before treatment, MoCA and MMSE scores were increased in both groups after treatment (P<0.001), with higher scores in the experimental group than those in the control group (P<0.001, P<0.05). After treatment, the relative abundance of Faecalibacterium, Clostridia, and Ruminococcaceae was increased in the experimental group compared with that before treatment (P<0.05). Moreover, the relative abundance of Faecalibacterium in the experimental group was higher than that in the control group (P<0.05). The total effective rate was 82.8% (24/29) in the experimental group, which was higher than 61.3% (19/31) in the control group (P<0.05). CONCLUSION Acupuncture could improve cognitive dysfunction in patients with MCI, and its mechanism may be related to increasing the relative abundance of butyrate-producing bacteria such as Faecalibacterium, Clostridia, and Ruminococcaceae, maintaining the intestinal barrier, and inhibiting related inflammatory responses.
Humans ; Acupuncture Therapy ; Gastrointestinal Microbiome ; Cognitive Dysfunction/psychology* ; Male ; Female ; Aged ; Middle Aged ; Acupuncture Points ; Treatment Outcome ; Aged, 80 and over ; Cognition

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*