OBJECTIVES: To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats. METHODS: Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated. RESULTS: BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month. CONCLUSION BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR.
Animals ; Hippocampus/pathology* ; Rats, Wistar ; Antioxidants/pharmacology* ; Berberine/therapeutic use* ; Cognition/drug effects* ; Male ; Lead Poisoning/metabolism* ; Chronic Disease ; Oxidative Stress/drug effects* ; Maze Learning/drug effects* ; Rats ; Lipid Peroxidation/drug effects* ; Malondialdehyde/metabolism*

OBJECTIVE: To explore the effects of acupuncture in comparison with sham acupuncture on cognitive functions in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In this randomized controlled trial, 31 RRMS patients in the acupuncture group were treated with traditional Chinese acupuncture based on the treatment principle of calming the mind, reinforcing qi and blood, and 31 patients in the control group were treated with sham acupuncture (shallow needling at non-acupuncture points) twice a week for 12 weeks. The primary outcome was the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) score, which was evaluated by a psychologist at baseline and after 12 weeks of treatment. The secondary outcomes were the Symptom Checklist 90-Revised (SCL-90-R), Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) scores. The participants were provided with contact information from the researchers with constant access to report any adverse symptoms. RESULTS: In total, 62 participants were enrolled and allocated to the acupuncture group (31 cases) or control group (31 cases). After 12 weeks of acupuncture treatment, BICAMS including Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-2 (CVLT-2) and delayed CVLT-2 scores were significantly improved in comparison with the control group (P<0.01). However, the changes in the Brief Visuospatial Memory Test-Revised (BVMT-R) and delayed BVMT-R scores related to visual/spatial memory did not differ significantly between the two groups (both P>0.05). The FSS, PSQI, and SCL-90-R scores were significantly reduced after 12-week treatment in the acupuncture group compared to the control group (P<0.05 or P<0.01). No life-threatening adverse events occurred throughout the study. CONCLUSIONS Twelve weeks of acupuncture treatment was effective in improving immediate and short-term auditory/verbal memory, attention and processing speed; reducing fatigue and decreasing sleep latency and the use of sleeping medications; alleviating depression, somatization, obsessive-compulsive and paranoid disorders in patients with RRMS. (Iranian Registry of Clinical Trials, No. IRCT20220101053582N1).
Humans ; Multiple Sclerosis, Relapsing-Remitting/physiopathology* ; Acupuncture Therapy ; Female ; Male ; Cognition/physiology* ; Adult ; Treatment Outcome ; Middle Aged

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

During long-duration manned space missions, the complex and extreme space environment exerts significant impacts on astronauts' physiological, psychological, and cognitive functions, thereby posing direct risks to mission safety and operational efficiency. As a key bridge between the brain and external devices, brain-computer interface (BCI) technology enables precise acquisition and interpretation of neural signals, offering a novel paradigm for human-machine collaboration in manned spaceflight. Non-invasive BCI technology shows broad application prospects across astronaut selection, mission training, in-orbit task execution, and post-mission rehabilitation. During mission preparation, multimodal signal assessment and neurofeedback training based on BCI can effectively enhance cognitive performance and psychological resilience. During mission execution, BCI can provide real-time monitoring of physiological and psychological states and enable intention-based device control, thereby improving operational efficiency and safety. In the post-mission rehabilitation phase, non-invasive BCI combined with neuromodulation may improve emotional and cognitive functions, support motor and cognitive recovery, and contribute to long-term health management. However, the application of BCI in space still faces challenges, including insufficient signal robustness, limited system adaptability, and suboptimal data processing efficiency. Looking forward, integrating multimodal physiological sensors with deep learning algorithms to achieve accurate monitoring and individualized intervention, and combining BCI with virtual reality and robotics to develop intelligent human-machine collaboration models, will provide more efficient support for space missions.
Brain-Computer Interfaces ; Humans ; Space Flight ; Astronauts/psychology* ; Neurofeedback ; Cognition ; Electroencephalography ; Man-Machine Systems

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

Objective:To explore various factors influencing speech recognition ability in patients with age-related hearing loss（ARHL） and to investigate the correlation between speech recognition ability and cognitive function. Methods:This case-control study enrolled 150 ARHL patients（experimental group） and 132 normal-hearing controls. Participants underwent relevant assessments of auditory function, cognitive function, and tinnitus severity. Various statistical analyses were performed to evaluate the results. Results:①The PBmax and MoCA scores were significantly lower in the ARHL group compared to the control group（P<0.05）. ②PBmax in the ARHL group was significantly influenced by multiple factors（P<0.05）. ③Negative correlations were observed between PBmax in the ARHL group and age, degree of hearing loss, duration of the disease, duration of the worst hearing loss, smoking status, and tinnitus severity（P<0.05）, while positive correlations were found between PBmax and education level, occupation type, frequency of verbal communication, and cognitive function level（P<0.05）. ④Higher education level, frequent verbal communication, and high cognitive function level were protective factors for PBmax in ARHL patients（P<0.05）, whereas the other factors were independent risk factors（P<0.05）. ⑤A significant correlation was found between PBmax and MoCA scores in the ARHL group, and this correlation between cognitive function and speech recognition ability remained significant across different degrees of hearing loss（<0.05）. Conclusion:Speech recognition ability in ARHL patients is influenced by multiple factors. Cognitive function demonstrates a robust, bidirectional association with speech recognition ability, even after adjusting for hearing loss severity.
Humans ; Case-Control Studies ; Middle Aged ; Male ; Female ; Aged ; Speech Perception ; Cognition ; Presbycusis/physiopathology* ; Adult ; Hearing Loss

OBJECTIVES: To explore the molecular mechanism by which miR-124 affects cognitive function of sleep-deprived rats. METHODS: Fifty-four adult male SD rats were randomized into 6 groups (n=9), including a normal control group, a sleep deprivation (SD) model group, and 4 intracerebral microinjection groups in which the rats were subjected to stereotactic injection of miR-124 agomir, miR-124 agomir NC, miR-124 antagomir, or miR-124 antagomir into the lateral ventricle 7 days before SD modeling. The cognitive functions of the rats were evaluated with Morris water maze test, and pathological changes in the hippocampus were observed using HE staining. The expression level of miR-124 in hippocampal tissues of the rats was detected with qRT-PCR, and the expression level of apoptosis-related proteins and signaling pathway proteins were determined using Western blotting. RESULTS: In Morris water maze test, the SD rat models treated with miR-124 agomir showed a significantly shorter escape latency and fewer platform crossings with increased percentage of time and swimming distance in the fourth quadrant as compared with those in SD model group, while the rats treated with miR-124 antagomir exhibited worsened performance in the test. In the SD rat models, treatment with miR-124 agomir obviously lessened pathological changes in the hippocampus, while treatment with miR-124 antagomir significantly worsened the pathological changes. Compared with those in SD model group, the miR-124 agomir-treated rats showed an increased hippocampal expression of miR-124 with upregulated protein expressions of PI3K, p-AKT/AKT, and Bcl-2 and downregulated expressions of Bax and caspase-3 proteins, while rats treated with miR-124 antagomir showed significantly decreased hippocampal expression of miR-124 with lowered expressions of PI3K, p-AKT/AKT and Bcl-2 proteins and increased Bax and caspase-3 protein expressions. CONCLUSIONS High expression of miR-124 alleviates SD-induced cognitive decline and neuronal apoptosis in rats by activating the PI3K/AKT signaling pathway.
Animals ; MicroRNAs/metabolism* ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Male ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cognition ; Rats ; Sleep Deprivation/metabolism* ; Apoptosis ; Maze Learning

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*