Pathogenesis Of Cognitive Impairment Research Articles

The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.

Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies. In AD, dysregulation of this axis contributes to amyloid-β accumulation and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. PD studies reveal that CXCL12/CXCR4 signaling influences dopaminergic neuron survival and microglial activation, affecting cognitive function. In MS, the axis modulates neuroinflammation and demyelination processes, impacting cognitive performance. ALS research indicates that the CXCL12/CXCR4/CXCR7 pathway is involved in motor neuron degeneration and associated cognitive deficits. Across these diseases, the axis influences neuroinflammation, synaptic plasticity, and neuronal survival through various signaling cascades, including PI3K/AKT, MAPK, and JAK/STAT pathways. Emerging evidence suggests that modulating this axis could provide neuroprotective effects and potentially alleviate cognitive symptoms. This review highlights the potential of the CXCL12/CXCR4/CXCR7 axis as a therapeutic target for addressing CI in neurodegenerative diseases. It also underscores the need for further research to fully elucidate its role and develop effective interventions, potentially leading to improved clinical management strategies for these devastating disorders.

CD8+T cells and monocytes were associated with brain alterations in human immunodeficiency virus-infected individuals with cognitive impairment.

Cognitive impairment (CI) continues to be a concern for people living with HIV-1 (PLWH) in the era of antiretroviral therapy (ART), yet the underlying mechanisms remain unclear. We aimed to elucidate the structural and functional brain alterations and peripheral immune profile of PLWH with CI, as well as the correlation between them. PLWH were divided into CI (n= 30) and cognitive normal (CN, n= 59) groups based on the Montreal Cognitive Assessment, and underwent multi-modal magnetic resonance imaging. Mass cytometry was utilized to profile immune cells, while the liquid chip technique was employed to measure plasma levels of cytokines and chemokines. Spearman correlation analyses were conducted for correlation analysis. Here, we found that the gray matter volume in left supramarginal gyrus was reduced, and the ReHo in the right middle frontal gyrus and the functional connectivity between right middle frontal gyrus and left postcentral gyrus were enhanced in CI group compared to CN group. Additionally, the frequencies of naïve CD8+T cells (Tn) and CD31lowCD8+ Tn were significantly correlated with gray matter volume in the left supramarginal gyrus. The amplitude of low frequency fluctuations in a specific brain region of frontal-middle lobe was negatively correlated with the frequencies of non-classical monocytes (nCM) and their subpopulations (CCR2lownCM, CD57lownCM and CD127+nCM), and positively associated with the plasma interleukin 25 and transforming growth factor-α levels. These findings suggest the association between peripheral immunity and the brain abnormalities in PLWH, highlighting a potential role of the immune-brain-cognition axis in the pathogenesis of CI in Chinese PLWH.

Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients.

The pathogenesis of cognitive impairment in schizophrenia (SCZ) remains unclear. Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor (BDNF) levels play a crucial role in the psychopathology of SCZ. However, their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated. To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ. The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ (SCZ group) and 80 healthy controls (HCs group) at the Huzhou Third Municipal Hospital between August 2021 and September 2023. ELISA was employed to measure the serum levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, and BDNF. The Chinese brief cognitive test (C-BCT) and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms. Compared to the HC group, the SCZ group exhibited elevated IL-1β and IL-6 levels, decreased BDNF levels, and reduced C-BCT scores (all P < 0.001). In SCZ, BDNF was negatively correlated with IL-6 (r = -0.324, P < 0.05). Information processing speed was negatively correlated with IL-6 (r = -0.315, P < 0.05) and positively with BDNF (r = 0.290, P < 0.05); attention, working memory, comprehensive ability, and executive function were negatively correlated with IL-1β and IL-6 (all P < 0.05) and positively with BDNF (all P < 0.05). Multiple regression analysis showed IL-6 influenced C-BCT dimensions (β = -0.218 to -0.327, all P < 0.05); attention and executive ability were influenced by IL-1β (β = -0.199 to -0.261, all P < 0.05); comprehensive executive ability was influenced by BDNF (β = 0.209, P < 0.05). Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

The entorhinal cortex and cognitive impairment in schizophrenia: A comprehensive review.

Schizophrenia, a severe mental illness characterized by cognitive impairment and olfactory dysfunction, remains an enigma with its pathological mechanism yet to be fully elucidated. The entorhinal cortex, a pivotal structure involved in numerous neural loop circuits related to olfaction, cognition, and emotion, has garnered significant attention due to its structural and functional abnormalities, which have been implicated in the pathogenesis of schizophrenia. This review focuses on the abnormal structural and functional changes in the entorhinal cortex in schizophrenia patients, as evidenced by neuroimaging, cellular biology, and genetic studies. These changes are posited to play a crucial role in the pathogenesis of cognitive impairment in schizophrenia. Furthermore, this review explores the various intervention strategies targeting the entorhinal cortex in current treatment modalities and proposes potential directions for future research endeavors, thereby providing a novel perspective on unraveling the complexity of neural mechanisms underlying schizophrenia and developing innovative therapeutic approaches for schizophrenia.

Hyperbaric Oxygen Improves Cognitive Impairment Induced by Hypoxia via Upregulating the Expression of Oleic Acid and MBOAT2 of Mice.

Cognitive impairment (CI) causes severe impairment of brain function and quality of life of patients, which brings a great burden to society. Cerebral hypoxia is an important factor in the pathogenesis of CI. Hyperbaric oxygen (HBO) therapy may mitigate hypoxia-induced CI, but its efficacy and mechanisms are not fully understood. In this study, a mice model of CI induced by hypoxia environment was established, then behavioral tests, pathological examination, metabolomic and lipidomic analyses, and molecular biology were used to assess the impact of HBO on hypoxia-induced CI. HBO was found to alleviate CI and pathological damage of hypoxia mice. Metabolomic, lipidomic, and molecular biology analyses showed that HBO increased the levels of oleic acid (OA) and membrane-bound O-acyltransferase 2 (MBOAT2), thereby altering the composition of membrane phospholipids (PLs) and reducing hypoxia-induced neuronal ferroptosis (FPT) to interfere with cognitive function in mice. In vitro experiments confirmed that OA and MBOAT2 led to membrane PL remodeling in a mutually dependent manner, affecting cell resistance to hypoxia-FPT. The results emphasized the combined effect value of OA and MBOAT2 in HBO for hypoxia-induced CI, and provided a novel perspective for the treatment of CI by HBO.

Распространенность когнитивных нарушений у пациентов с рассеянным склерозом

Multiple sclerosis (MS) is a chronic autoimmune disorder that manifests itself in progressive neurodegeneration causing a broad spectrum of cognitive deficits in the patients. Cognitive impairment being an essential component of the clinical picture of the disease come in a variety of manifestations and significantly lower the MS patients’ quality of life. This paper reports contemporary views on the prevalence and pathogenesis of cognitive impairment; the data of original studies involving patients with multiple sclerosis are provided.

Acupuncture and moxibustion therapy for cognitive impairment: the microbiome-gut-brain axis and its role.

Cognitive impairment poses a significant burden on individuals, families, and society worldwide. Despite the lack of effective treatment strategies, emerging evidence suggests that the microbiome-gut-brain (MGB) axis may play a critical role in the pathogenesis of cognitive impairment. While targeted treatment is not yet comprehensive, recently, acupuncture and moxibustion therapy has participated increasingly in the treatment of degenerative diseases and has achieved a certain therapeutic effect. In this review, the possible mechanisms by which acupuncture and moxibustion therapy may improve cognitive impairment through the MGB axis are reviewed, including regulating gut microbial homeostasis, improving intestinal inflammation mediated by the neuroendocrine-immune system, and enhancing intestinal barrier function. We also discuss common acupoints and corresponding mechanism analysis to provide insights into further exploration of mechanisms that target the MGB axis and thereby intervene in cognitive impairment.

Research hotspots and trends on NF-κB in cognitive impairment: a bibliometric analysis.

Cognitive impairment (CI) endangers the physical and mental health of patients in a significant manner, and it is expected that the number of people with CI in China will rise to 45.33 million by 2050. Therefore, CI has become a popular research topic. Inflammatory damage plays a key role in the pathogenesis of CI, and NF-κB is an important inflammatory signaling pathway. However, no bibliometric analysis regarding the relationship between CI and NF-κB has been reported. A bibliometric analysis regarding NF-κB and CI from 1 January 2008 to 12 December 2023 was conducted in the Science Citation Index-Expanded of the Web of Science Core Collection. The frontiers, hotspots, and trends of research regarding the role of NF-κB in CI were identified. VOSviewer and CiteSpace were used to analyze the retrieved articles and identify the author, country, institution, and keywords, as well as co-cited authors, co-cited journals, and co-cited references. We analyzed 1,468 original articles and reviews. Publications on NF-κB in CI began in 2010 and increased sharply in 2018. Hong Hao was the most represented author, having published 19 articles, and Chinese authors published more studies than those from other countries. China Pharmaceutical University published the most papers; however, the United States has a strong influence and demonstrates international cooperation. The keywords "apolipoprotein e" and "therapeutic target" demonstrated strong citation bursts, and this tendency may persist in the upcoming years. Neuroinflammation demonstrated a strong influence in research regarding NF-κB in CI. Gut microbiota and ketogenic diet also play an important role in NF-κB in CI. This bibliometric analysis and visualization using VOSviewer and CiteSpace revealed that the role of NF-κB in CI has become a research hotspot. The results of this study indicated that "neuroinflammation," "microglial," and "pathway" remain hotspots for future research. However, studies regarding NF-κB in CI have predominantly focussed on basic research; future research should include therapeutic targets, microbiota, and ketogenic diet.

Topological regularization of networks in temporal lobe epilepsy: a structural MRI study.

Patients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE. Thirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients. Although small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p < 0.001), normalized clustering coefficient (p < 0.001), and a decrease in the transfer coefficient (p < 0.001) compared with the NC group. Locally, TLE patients showed a decrease in nodal betweenness and degree in the left lingual gyrus, right middle occipital gyrus and right thalamus compared with the NC group (p < 0.05, uncorrected). The degree of structural networks in both TLE (Temporal Lobe Epilepsy) and control groups was distributed exponentially in truncated power law. In addition, the stability of random faults in the structural covariance network of TLE patients was stronger (p = 0.01), but its fault tolerance was lower (p = 0.03). The objective of this study is to investigate the potential neurobiological mechanisms associated with temporal lobe epilepsy through graph theoretical analysis, and to examine the topological characteristics and robustness of gray matter structural networks at the network level.

Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case-control study.

The pathogenesis of cognitive impairment (CI) in coronary artery disease (CAD) patients is still unclear and numerous influence factors could affect the CI status. The current studies suggest that sleep quality and behavior pattern are significant influence factors associated with CAD susceptibility. A total of 223 participants including 90 CAD patients with CI and 133 controls were enrolled into this retrospective study. Demographic information, laboratory test results, clinical diagnostic data, and questionnaire survey were collected to recognize the influencing factors of CI in CAD patients. Appropriate statistical methods are used to analyze these collected data. Univariate analysis results of demographic information, laboratory test results, and questionnaire survey data revealed that the differences in fatigue symptom, age, HDL, TG, and sleep quality were statistically significant (p = 0.006, p = 0.000, p = 0.019, p = 0.028, and p = 0.037, respectively). Logistic regression analysis showed that age, fatigue, and sleep quality were the influence factors for CI in CAD population (p = 0.000, p = 0.035, and p = 0.017). Sleep quality, fatigue, and age were associated with the increased susceptibility of CI in CAD patients. Both CI state and its related factors were involved in the pathological process of CAD, these findings could offer additional information for the prevention and control of CAD.

Mechanism of cognitiveimpairment induced by d-galactose and l-glutamate through gut-brain interaction in tree shrews.

d-Galactose (d-gal) and l-glutamate (l-glu) impair learning and memory. The mechanism of interaction between the gutmicrobiome and brain remains unclear. In this study, a model of cognitive impairment was induced in tree shrews by intraperitoneal (ip) injection of d-gal (600mg/kg/day), intragastric (ig) administration with l-glu (2000mg/kg/day), and the combination of d-gal (ip, 600mg/kg/day) and l-glu (ig, 2000mg/kg/day). The cognitive function of tree shrews was tested by the Morris water maze method. The expression of Aβ1-42 proteins, the intestinal barrier function proteins occludin and P-glycoprotein (P-gp), and the inflammatory factors NF-κB, TLR2, and IL-18 was determined by immunohistochemistry. The gutmicrobiome was analyzed by 16SrRNA high-throughput sequencing. After administering d-gal and l-glu, the escape latency increased (p<.01), and the times of crossing the platform decreased (p<.01). These changes were greater in the combinedadministration of d-gal and l-glu (p<.01). The expression of Aβ1-42 was higher in the perinuclear region of the cerebral cortex (p<.01) and intestinal cell (p<.05). There was a positive correlation between the cerebral cortex and intestinal tissue. Moreover, the expression of NF-κB, TLR2, IL-18, and P-gp was higher in the intestine (p<.05), while the expression of occludin and the diversity of gut microbes were lower, which altered the biological barrier of intestinal mucosal cells. This study indicated that d-gal and l-glu could induce cognitiveimpairment, increase the expression of Aβ1-42 in the cerebral cortex and intestinal tissue, decrease the gut microbial diversity, and alter theexpression of inflammatory factors in the mucosal intestines. The dysbacteriosis may produce inflammatory cytokines to modulate neurotransmission, causing the pathogenesis of cognitiveimpairment. This study provides a theoretical basis to explore the mechanism of learning and memory impairment through the interaction of microbes in the gut and the brain.

Pathomechanisms of cognitive impairment in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by early postural instability and falls, oculomotor dysfunction (vertical supranuclear gaze palsy), parkinsonism with poor response to levodopa, pseudobulbar palsy, and cognitive impairment. This four-repeat tauopathy is morphologically featured by accumulation of tau protein in neurons and glia causing neuronal loss and gliosis in the extrapyramidal system associated with cortical atrophy and white matter lesions. Cognitive impairment being frequent in PSP and more severe than in multiple system atrophy and Parkinson disease, is dominated by executive dysfunction, with milder difficulties in memory, and visuo-spatial and naming dysfunctions. Showing longitudinal decline, it has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, such as involvement of cholinergic and muscarinergic dysfunctions, and striking tau pathology in frontal and temporal cortical regions associated with reduced synaptic density. Altered striatofrontal, fronto-cerebellar, parahippocampal, and multiple subcortical structures, as well as widespread white matter lesions causing extensive connectivity disruptions in cortico-subcortical and cortico-brainstem connections, support the concept that PSP is a brain network disruption disorder. The pathophysiology and pathogenesis of cognitive impairment in PSP, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for adequate treatment to improve the quality of life of patients with this fatal disease.

Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract

Brain aging is a crucial risk factor for several neurodegenerative disorders and dementia. The most affected cognitive function is memory, worsening early during aging. Inflammation and oxidative stress are known to have a role in pathogenesis of cognitive impairments, and a link exists between aging/frailty and immunosenescence/inflammaging. Based on anti-aging properties, medicinal mushrooms represent a source to develop medicines and functional foods. In particular, Hericium erinaceus (He) displays several actions ranging from boosting the immune system to fighting senescence, due to its active ingredients/metabolites. Among these, Ergothioneine (ERGO) is known as the longevity vitamin. Currently, we demonstrated the efficacy of an ERGO-rich He primordium extract (He2) in preventing cognitive decline in a murine model of aging. We focused on recognition memory deterioration during aging, monitored through spontaneous behavioral tests assessing both memory components and frailty index. A parallel significant decrease in key markers of inflammation and oxidative stress, i.e., IL6, TGFβ1, GFAP, Nrf2, SOD1, COX2, NOS2, was revealed in the hippocampus by immunohistochemistry, accompanied by an enhancement of NMDAR1and mGluR2, crucially involved in glutamatergic neurotransmission. In summary, we disclosed a selective, preventive and neuroprotective effect of He2 on aged hippocampus, both on recognition memory as well on inflammation/oxidative stress/glutamate receptors expression.

HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load.

There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment-naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a tyrosine at position 45 (45Y) as a signature for neurocognitive impairment and histidine (45H) as a signature in the non-impaired individuals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load, and 60% lower absolute CD4-T cell count compared with those without the signature. Additionally, we identified four conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5-21), LGQYIY (42-47), TYGDTW (49-54), and PEDQGPQREPYNEW (5-18), that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitive impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery.

Implication of Hypotension in the Pathogenesis of Cognitive Impairment and Brain Injury in Chronic Liver Disease.

The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent neuronal injury and irreversibility. The pathophysiology of HE primarily implicates a strong role for hyperammonemia, but it is believed other pathogenic factors are involved. The fibrotic scarring of the liver during the progression of chronic liver disease (cirrhosis) consequently leads to increased hepatic resistance and circulatory anomalies characterized by portal hypertension, hyperdynamic circulatory state and systemic hypotension. The possible repercussions of these circulatory anomalies on brain perfusion, including impaired cerebral blood flow (CBF) autoregulation, could be implicated in the development of HE and/or permanent brain injury. Furthermore, hypotensive insults incurring during gastrointestinal bleed, infection, or liver transplantation may also trigger or exacerbate brain dysfunction and cell damage. This review will focus on the role of hypotension in the onset of HE as well as in the occurrence of neuronal cell loss in cirrhosis.

Integrated Clinical Features with Plasma and Multi-modal Neuroimaging Biomarkers to Diagnose Mild Cognitive Impairment in Early Drug-Naive Parkinson's Disease.

The pathogenesis of cognitive impairment in Parkinson's disease (PD) patients remains unclear, and there is no ideal diagnostic tool available at present. We assessed integrated clinical features with plasma and multi-modal neuroimaging biomarkers to identify mild cognitive impairment (MCI) in early drug-naive PD patients. 49 early drug-naive PD patients, including 26 with MCI (PD-MCI) and 23 with normal cognition (PD-NC), and 20 controls were recruited. Plasma markers [α-synuclein, beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), and phosphorylated Tau 181 (p-Tau181) levels], functional connectivity (FC) of the default mode network, and cortical thickness (CTh) were evaluated to identify PD-MCI. The PD-MCI group had significantly higher plasma p-Tau181 levels and p-Tau181/Aβ42 ratio and lower Aβ42/Aβ40 ratio compared to the PD-NC group. Compared to PD-NC, the PD-MCI group showed increased FC between left posterior cingulate cortex (pCC) and the left parahippocampal gyrus (PHG), and between the right hippocampal formation and the left anterior cingulate and paracingulate gyri, and the right middle temporal gyrus. Additionally, the PD-MCI group had thinner cortex thickness in the right lateral occipital and frontal pole compared to the PD-NC group. The final model combining clinical characteristics and several variables (age, sex, plasma p-Tau181 level, Aβ42/Aβ40 ratio, the right lateral occipital CTh, and the FC value between the left pCC and left PHG) had the highest diagnostic accuracy for PD-MCI (AUC = 0.987, 95% CI 0.903-1.000; p = 0.001 compared to age and sex alone). The combination of clinical features, plasma biomarkers, and multi-modal neuroimaging biomarkers can identify early cognitive decline in PD patients.

Combination of Donepezil and Memantine Attenuated Cognitive Impairment Induced by Mixed Endocrine-Disrupting Chemicals: an In Silico Study.

Little is known about the effects of endocrine-disrupting chemicals (EDCs) and the combination of memantine and donepezil on the pathogenesis of cognitive impairment. Here, we aimed to identify in silico the molecular mechanisms of the combination of memantine and donepezil that combat cognitive impairment induced by nine common EDCs using GeneMania, AutoDock Vina, Metascape, SwissADME, MIENTURNET, and miRNAsong. We observed that the mixture of memantine and donepezil had therapeutic effects on mixed EDC-induced cognitive impairment via five genes (TNF, ACHE, BAX, IL1B, and CASP3). With ACHE and TNF, donepezil and memantine both had a high docking score, respectively. The predominant connections among five mutual genes were physical interactions (77.6%). The major pathways associated with memantine and donepezil countering cognitive impairment generated by mixed EDCs were discovered to be "AGE-RAGE signaling pathway in diabetic complications," "pro-survival signaling of neuroprotectin D1," and "non-alcoholic fatty liver disease." The miRNAs and transcription factors implicated in memantine and donepezil protecting against mixed EDCs were hsa-miR-128-3p and hsa-miR-34a-5p, NFKB1, NFKB2, IRF8, and E2F4. The sponges' tertiary structure predictions for two major miRNAs were provided. The physicochemical and pharmacokinetic properties of memantine and donepezil highlighted the need for a therapeutic combination of these medications to treat cognitive impairment.

Identifying and revealing different brain neural activities of cognitive subtypes in early course schizophrenia.

BackgroundCognitive subtypes of schizophrenia may exhibit different neurobiological characteristics. This study aimed to reveal the underlying neurobiological features between cognitive subtypes in the early course of schizophrenia (ECS). According to prior studies, we hypothesized to identify 2–4 distinct cognitive subtypes. We further hypothesized that the subtype with relatively poorer cognitive function might have lower brain spontaneous neural activity than the subtype with relatively better cognitive function.MethodCognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Resting-state functional magnetic resonance imaging scanning was conducted for each individual. There were 155 ECS individuals and 97 healthy controls (HCs) included in the subsequent analysis. Latent profile analysis (LPA) was used to identify the cognitive subtypes in ECS individuals, and amplitude of low-frequency fluctuations (ALFFs) was used to measure brain spontaneous neural activity in ECS individuals and HCs.ResultsLPA identified two cognitive subtypes in ECS individuals, containing a severely impaired subtype (SI, n = 63) and a moderately impaired subtype (MI, n = 92). Compared to HCs, ECS individuals exhibited significantly increased ALFF in the left caudate and bilateral thalamus and decreased ALFF in the bilateral medial prefrontal cortex and bilateral posterior cingulate cortex/precuneus (PCC/PCu). In ECS cognitive subtypes, SI showed significantly higher ALFF in the left precentral gyrus (PreCG) and lower ALFF in the left PCC/PCu than MI. Furthermore, ALFFs of left PreCG were negatively correlated with several MCCB cognitive domains in ECS individuals, while ALFF of left PCC/PCu presented opposite correlations.ConclusionOur findings suggest that differences in the brain spontaneous neural activity of PreCG and PCC/PCu might be the potential neurobiological features of the cognitive subtypes in ECS, which may deepen our understanding of the role of PreCG and PCC/PCu in the pathogenesis of cognitive impairment in schizophrenia.

Current modeling approaches to experimental cognitive impairment (a literature review)

The aim of the work is to review the professional literature sources from the scientific database PubMed mainly for the last 20 years analyzing the modern view on approaches to experimental modeling of cognitive impairment. Materials and methods. A review of the scientific literature over the past 20 years was performed. The lack of requisite knowledge about the pathogenesis of cognitive impairment and the wide range of risk factors for these conditions continue to be major challenges in the development of guidelines on early diagnosis and treatment. The literary analysis suggests that all modeling approaches to experimental cognitive impairment are currently divided into two groups: cell culture and animal models. Conclusions. Experimental modeling of cognitive impairment remains important in addition to clinical and population-based studies. In recent years, the problem of selecting an adequate model to study cognitive impairment, which is a central clinical manifestation of various neurological diseases (Alzheimer’s and Parkinson’s diseases, traumatic brain injury, vascular, demyelinating, and infectious diseases, metabolic aberrations and hormonal imbalance, neurodegenerative diseases of the central nervous system) is becoming increasingly relevant. The choice of model and experimental material – animals or cultures (invertebrate and mammalian cells) is based on a clear understanding of the study design and depends on the ultimate goal of research.

LONG NONCODING RNA UPREGULATES ADAPTER SHCA PROTEIN EXPRESSION TO PROMOTE COGNITIVE IMPAIRMENT AFTER CARDIAC ARREST AND RESUSCITATION.

Aim: More patients are resuscitated from cardiac arrest and cardiopulmonary resuscitation (CA/CPR) due to advances in medical care. However, the burden now lies with post-cardiac arrest cognitive impairment in CA/CPR survivors. Based on our previous study, we aimed to further confirm the correlation between the long noncoding RNA-promoting ShcA (lncRNA-PS)/Src homology and collagen A (ShcA) axis and CA/CPR-induced cognitive impairment in molecular, cellular, and tissue levels. Methods and Results: The in vivo experiments were based on a mouse model of CA/CPR, while oxygen-glucose deprivation and reoxygenation was used as a cell model in vitro. Conditional ShcA suppression in neurons of the hippocampal CA1 region was achieved by cyclization recombinase of bacteriophage P1 recognizing DNA fragment locus of x-over P1 site (Cre/LoxP recombination system). Genetic manipulation of HT22 was achieved by lentivirus targeting lncRNA-PS and ShcA. Neurological function score was remarkably decreased, and cognitive function was affected after restoration of spontaneous circulation. LncRNA-PS and ShcA overexpression after CA/CPR, mainly happened in neurons of hippocampal CA1 region, was observed by in situ hybridization and immunofluorescence. Neuronal ShcA knockdown in hippocampal CA1 region before CA/CPR attenuated cognitive impairment after CA/CPR. ShcA deficiency protected HT22 cell line against oxygen-glucose deprivation and reoxygenation by inhibiting inflammation and apoptosis. In vitro upregulation of lncRNA-PS elevated ShcA expression, which was reversed by knockdown of ShcA. Conclusions: This study revealed that lncRNA-PS/ShcA axis is critically involved in the pathogenesis of cognitive impairment after CA/CPR. By inhibiting ShcA expression in neurons of the hippocampal CA1 region could improve the survival outcomes in mice after CA/CPR.