Neurons In Brain Research Articles

Drosulfakinin signaling encodes early-life memory for adaptive social plasticity.

Drosophila establishes social clusters in groups, yet the underlying principles remain poorly understood. Here we performed a systemic analysis of social network behavior (SNB) that quantifies individual social distance (SD) in a group over time. The SNB assessment in 175 inbred strains from the Drosophila Genetics Reference Panel showed a tight association of short SD with long developmental time, low food intake, and hypoactivity. The developmental inferiority in short-SD individuals was compensated by their group culturing. By contrast, developmental isolation silenced the beneficial effects of social interactions in adults and blunted the plasticity of SNB under physiological challenges. Transcriptome analyses revealed genetic diversity for SD traits, whereas social isolation reprogrammed select genetic pathways, regardless of SD phenotypes. In particular, social deprivation suppressed the expression of the neuropeptide Drosulfakinin (Dsk) in three pairs of adult brain neurons. Male-specific DSK signaling to Cholecystokinin-like receptor 17D1 mediated the SNB plasticity. In fact, transgenic manipulations of the DSK neuron activity were sufficient to imitate the state of social experience. Given the functional conservation of mammalian Dsk homologs, we propose that animals may have evolved a dedicated neural mechanism to encode early-life experience and transform group properties adaptively.

Astrocytes contribute to toll-like receptor 2-mediated neurodegeneration and alpha-synuclein pathology in a human midbrain Parkinson’s model

BackgroundParkinson’s disease (PD) is characterised by degeneration of ventral midbrain dopaminergic (DA) neurons and abnormal deposition of α-synuclein (α-syn) in neurons. Activation of the innate immune pathogen recognition receptor toll-like receptor 2 (TLR2) is associated with exacerbation of α-syn pathology. TLR2 is increased on neurons in the PD brain, and its activation results in the accumulation and propagation of α-syn through autophagy inhibition in neurons. In addition to the aggregation and propagation of pathological α-syn, dysfunction of astrocytes may contribute to DA neuronal death and subsequent clinical progression of PD. However, the role of astrocytes in TLR2-mediated PD pathology is less explored but important to address, given that TLR2 is a potential therapeutic target for PD.MethodsInduced pluripotent stem cells from three controls and three PD patients were differentiated into a midbrain model comprised of neurons (including DA neurons) and astrocytes. Cells were treated with or without the TLR2 agonist Pam3CSK4, and α-syn pathology was seeded using pre-formed fibrils. Confocal imaging was used to assess lysosomal function and α-syn pathology in the different cell types, as well as DA neuron health and astrocyte activation.ResultsTLR2 activation acutely impaired the autophagy lysosomal pathway, and potentiated α-syn pathology seeded by pre-formed fibrils in PD neurons and astrocytes, leading to degeneration and loss of DA neurons. The astrocytes displayed impaired chaperone-mediated autophagy reducing their ability to clear accumulated α-syn, and increases of A1 neurotoxic phenotypic proteins SerpinG1, complement C3, PSMB8 and GBP2. Moreover, the phenotypic changes in astrocytes correlated with a specific loss of DA neurons.ConclusionsTaken together, these results support a role for astrocyte dysfunction in α-syn accumulation and DA neuronal loss following TLR2 activation in PD.

Role of RNA m6A reader YTHDF2 in neurodegeneration of the aged mice

Objective: To investigate the role of RNA m6A reader YTHDF2 in neurodegeneration of the aged mice. Methods: Eighteen 18-month-old control C57BL/6 mice and 22 Ythdf2 conditional knockout (cKO) mice of the same age (that exhibited significant aging characteristics) were used. Five pairs of mice were used for morphological analysis. Thirteen control mice and 17 cKO mice were used for behavioral experiments. Immunofluorescence analysis was performed to detect the expression of YTHDF2 in the brains of 18-month-old C57BL/6 mice. After establishing the neural progenitor cell-specific knockout mice of Ythdf2, their phenotypes were analyzed through comparison of body weight, brain weight and H&E staining. Subsequently, immunohistochemistry and immunofluorescence analyses were used to detect the expression of various neural cell-specific markers in the aged control mice and Ythdf2 cKO mice. Finally, behavioral tests, including the open field test, new object recognition, and water maze, were used to assess the levels of anxiety, depression, learning and memory abilities. Results: Immunofluorescence staining showed that YTHDF2 was mainly expressed in the neurons. Compared with the age-matched control mice, there was no significant change in the body weight of the Ythdf2 cKO mice, but the brain weight decreased significantly (P<0.05). The immunostaining showed that Ythdf2 cKO mice had fewer neurons, fewer astrocytes with defective morphology, more microglia and activation of microglia (P<0.05). Behavioral tests showed that the aged Ythdf2 cKO mice exhibited impaired movement, learning and memory abilities (P<0.05). Conclusions: YTHDF2 is mainly expressed in the neurons of the aged brain. Conditional knockout of Ythdf2 causes quantitative and structural abnormalities in hippocampal neuronal cells, and impairs motor ability and learning and memory of the aged mice, suggesting that YTHDF2 plays an important role in neurodegeneration of the aged mice.

Regulation of sleep amount by CRTC1 via transcription ofCrhin mice

The cAMP-response element binding protein (CREB) is required for regulation of daily sleep amount, whereas gain-of-function of CREB-regulated transcription coactivator 1 (CRTC1) causes severe insomnia in mice. However, the physiological functions of CRTCs and their downstream target genes in the regulation of sleep amount remain unclear. Here, we use adult brain chimeric (ABC)-expression/knockout platform for somatic genetics analysis of sleep in adult male mice. ABC-expression of constitutively active mutant CRTC1/2CAin the mouse brain neurons significantly reduces the amount of non-rapid eye movement sleep (NREMS) and/or REMS. Consistent with that SIK3 phosphorylates and inhibits CRTCs, ABC-expression of CRTC1/2/3CArescues the hypersomnia phenotype ofSleepy(Sik3Slp) mice. While ABC-Crtc2KOorCrtc3KOcauses no sleep phenotype, ABC-Crtc1KOor ABC-expression of dominant-negative CRTC (dnCRTC) results in modest reduction of NREMS amount accompanied with elevated NREMS delta power. Moreover, ABC-expression of CRTC1CAor dnCRTC in the excitatory neurons causes bidirectional changes of NREMS/REMS amount and/or NREMS delta power, whereas expression of CRTC1CAin the inhibitory neurons decreases REMS amount and increases NREMS delta power. The ability of CRTC1CAto regulate sleep requires its transactivation domain and CREB-binding domain and is dependent on CREB. Furthermore, we showed that inducible ABC-expression of corticotropin releasing hormone (Crh) and brain-derived neurotrophic factor (Bdnf)–two target genes of CRTCs–significantly reduces daily sleep amount. Notably, ABC-CrhKO, but notBdnfKO, rescues the insomnia phenotype of ABC-CRTC1CAmice. Taken together, these results indicate that CREB-CRTC1 complex regulates daily sleep amount by modulating the transcription ofCrhin the mouse brain neurons.Significance StatementCRTCs function as coactivators for CREB, a transcription factor required for the regulation of daily sleep amount in mice. Here, we found that CRTC1/2/3 function similarly to suppress NREMS and REMS in a CREB-dependent manner. Consistent with that CRTCs are substrates of SIK3 kinase, expression of constitutive active mutant CRTCsCArescue the hypersomnia phenotype ofSleepy(Sik3Slp) mice. Furthermore, we showed that CRTC1 reduces NREMS amount by upregulating the expression of neuropeptide CRH. These results elucidate the mechanism by which CRTCs regulates sleep amount and suggest a potential transcriptional mechanism in the stress-induced sleep/wake regulation.

LRP1-mediated p-tau propagation contributes to cognitive impairment after chronic neuropathic pain in rats.

Trigeminal neuralgia (TN) is a prevalent chronic neuropathic pain syndrome characterized by severe pain, often accompanied by cognitive dysfunction and cerebral degeneration. However, its mechanisms remain poorly understood. Hyperphosphorylation of tau protein (p-tau) is often seen in neurodegenerative disorders such as Alzheimer's disease (AD). LRP1 expression on brain neurons and microglial cells is believed to facilitate the propagation of p-tau. We established a TN rat model via infraorbital nerve chronic constrictive injury (ION-CCI). Once the model was established, we investigated the association between p-tau and cognitive impairment in TN rats by evaluating behavioral and degenerative markers. During the initial phase, we noted an increase in p-tau level in the prefrontal cortex and hippocampal tissues of TN rats. The accompanied impaired learning and memory abilities suggested cognitive dysfunction. Blocking p-tau synthesis by orally administering a protein phosphatase and by injecting adenoviral vectors targeting LRP1 into the lateral ventricle of rats ameliorated cognitive impairment. This suggests that cognitive decline in TN rats is linked to elevated p-tau levels. Our findings show that LRP1-mediated p-tau propagation may drive cognitive impairment associated with neuropathic pain in TN rats.

Santiago Ramón y Cajal: Artistic legacy in Science, 90 years later

Ninety years after his death in 1934, the artistic beauty of the innovative brain images created by physician and histologist Santiago Ramón y Cajal, as well as his revolutionary neuroanatomical theory, remains relevant today. As a scientist who isolated brain nerve cells, he visualized them as physically distinct entities, answering one of the most crucial questions of his time. Prior to his work, the prevailing belief was in the reticular theory, which suggested that nervous tissue was continuous and formed a network of interconnected cells. His anatomical studies helped establish the foundations of modern neuroscience. Cajal, who worked in solitude for many years, embodied one of the most important virtues of a scientist in his life: perseverance.

Effect of calcium ions on the aggregation of highly phosphorylated tau

Tau is typically an axonal protein, but in neurons of brains affected by Alzheimer's disease (AD), aggregation of hyperphosphorylated tau in the somatodendritic compartment causes neuronal death. We have previously demonstrated that tau mRNA is transported within dendrites and undergoes immediate translation and hyperphosphorylation of AD epitopes in response to NMDA receptor stimulation. Although this explains the emergence of hyperphosphorylated tau in dendrites, the relationship between tau hyperphosphorylation and aggregation is not well understood. In this study, we found that recombinant highly phosphorylated tau purified from NG108-15 rodent neuroblastoma/glioma cells transfected with both tau and GSK3β expression vectors bound calcium ions and formed sarkosyl-insoluble aggregates. In addition, thioflavin T analysis revealed that this highly phosphorylated tau tended to aggregate on its own, further facilitated by calcium ions. When NG108-15 cells expressing the highly phosphorylated tau were treated with calcium ionophore, sarkosyl-insoluble tau was generated. Interestingly, these cells exhibited resistance to both calcium ionophore-induced cytotoxicity and glutamate-induced excitotoxicity. We further found that sarkosyl-insoluble phosphorylated tau was increased in cultured hippocampal neurons due to glutamate-induced hyperactivity. Our data suggest that hyperphosphorylated tau synthesized in response to NMDA receptor stimulation contributes to regulation of neuronal activity by binding calcium ions, but that this calcium binding may cause tau to adopt an aggregated form.

Design of experiments and artificial neural networks as useful tools in the optimization of analytical procedure.

Developing the analytical procedure requires estimating what independent variables will be tested and at what levels. There are statistical models that enable the optimization of the process. They involve statistical analysis, which indicates the crucial factors for the process and the potential interactions between the analyzed variables. Analysis of variance (ANOVA) is applied in the evaluation of the significance of the independent variables and their interactions. The most commonly used chemometric models are Box-Behnken Design, Central Composite Design and Doehlert Design, which are second-order fractional models. The alternative may be the artificial neural networks (ANN), whose structure is based on the connection of neurons in the human brain. They consist of the input, hidden and output layer. In such analysis, the activation functions must be defined. Both approaches might be useful in planning the analytical procedure, as well as in predicting the response prior to performance the measurements. The proposed procedures may be applied for polymeric systems.

Eighty-six billion and counting: do we know the number of neurons in the human brain?

Through statistical analysis and comparison of different studies, Alain Goriely challenges the widely accepted figure of 86 billion neurons in the human brain, and argues that the actual number is uncertain, with estimates ranging between 61 and 99 billion.

Potential of soybean-velvet bean combination tempe in improving cognitive function

Velvet bean is a native Indonesian legume containing L-dopa, yet it remains underutilized. The aim of this study was to analyze the effects of different types of tempe (soybean, velvet bean, and their combination) on cognitive function, brain histology, dopamine levels, and serum β-amyloid in rats, as well as to identify the parameters most influencing cognitive function, including brain mass and volume, hippocampal neuron count, and dopamine and β-amyloid levels. An experimental study was conducted using a completely randomized design with one factor: the protein source of diet. Five rat groups were included based on protein sources: non-protein, casein control, soybean tempe flour, velvet bean tempe flour, and a combination of soybean and velvet bean tempe flour. This study examined cognitive performance by measuring maze completion time, while brain mass and volume, hippocampus histology for neuron cell counts in the dentate gyrus section, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3), brain dopamine and β-amyloid serum levels were measured after eight weeks of intervention. Our data indicated that rats deprived of protein had significantly slower maze completion times (p&lt;0.001), underscoring the importance of protein in cognitive processes. Rats treated with non-protein rations had significantly lighter brain masses (p&lt;0.001) than other treatments. Histological analysis of the hippocampus showed that the three types of tempe rations helped maintain the number and density of neuron cells in the dentate gyrus and CA3 of the hippocampus. Additionally, the protein in the ration could increase dopamine levels and suppress serum β-amyloid levels. There was a strong correlation between brain volume and neuron cell density in the dentate gyrus section of the hippocampus with cognitive function. These results highlight the promising role of combination tempe in increasing cognitive function, brain mass and volume, dopamine levels, and suppressing serum β-amyloid.

Eleutheroside B alleviates oxidative stress and neuroinflammation by inhibiting the JAK2/STAT3 signaling pathway in a rat high altitude cerebral edema model.

High altitude cerebral edema (HACE) is a condition where the central nervous system experiences severe impairment as a result of sudden oxygen deprivation at high elevations. At present, effective measures for preventing and treating this condition are still lacking. Eleutheroside B (EB), the primary natural active compound found in the Eleutheroside senticosus, has demonstrated various biological functions. It has also shown significant potential in addressing acute mountain sickness and various neurological disorders. However, additional investigation is required to explore the potential protective effects and its underlying mechanisms of EB on HACE. The male rats received pre-treatment with either vehicle, EB 100mg/kg or 50mg/kg, Dexamethasone 4mg/kg, or coumermycin A1 100μg/kg. To simulate the hypobaric hypoxia environment at a plateau of 6,000m, a hypobaric hypoxia chamber was utilized. The therapeutic effects of EB were assessed through measurements of brain water content, histopathological observation, and evaluation of oxidative stress and inflammatory factors using immunofluorescence and ELISA. Furthermore, molecular docking, molecular dynamics simulation and Western blot were employed to clarify its molecular mechanism. Through these analyses, the underlying mechanism by which EB on HACE was identified. Pre-treatment with EB demonstrated a significant protective effect against HACE by effectively reducing brain water content, down-regulating HIF-1α and AQP4 protein expression induced by hypoxia and reversing pathological changes in brain tissue and neuron damage. Compared to the group treated with HACE alone, the group pre-treated with EB showed a significant reduction in levels of ROS and MDA, as well as an increase in GSH. In addition, pre-treatment with EB led to a significant decrease in the levels of IL-1β, IL-6, and TNF-α. Molecular docking and dynamics simulations indicated that EB has a strong binding affinity to the JAK2/STAT3 signaling pathway. Western blot further confirmed that EB significantly downregulated the expression of JAK2/STAT3 related proteins in the brain tissue of HACE rats. Additionally, coumermycin A1, an agonist of the JAK2, reversed the anti-oxidative stress and neuroinflammation against HACE of EB. EB exerts its antioxidant stress and anti-neuroinflammatory effects by inhibiting the JAK2/STAT3 signaling pathway in a rat HACE model.

N-Cadherin — A Potential Target for Psychopharmacology

Glycoprotein N-cadherin (Neuronal cadherin) belongs to the family of calcium-dependent cell adhesion molecules, representing a key element that carries out intercellular contacts in brain neurons. However, it is involved not only in the mechanical connection of neurons, but also influences the specifics of the further development and functional state of the neuron. This is due to the active interaction of N-cadherin with many proteins at the pre- and post-synapse, initiating a cascade of reactions that provide such processes as long-term potentiation (underlying learning and memory), morphogenesis, neuronal recognition, activation of receptors (NMDA and AMPA types), regulation of cytoskeleton formation. This polyfunctionality is necessary for specific neurons to connect to each other in a certain way, and such adhesion leads to the coordination of cell behavior through intercellular signaling and spatio–temporal control of differential gene expression. Mutations in the genes responsible for the expression of N-cadherin lead to various disorders of the functional activity of the synapse and the processes of spatial orientation and memory. Thus, involvement in important neuroplastic processes regulating cognitive functions and behavior determines interest in studying the effect of drugs on N-cadherin. In particular, N-cadherin deserves closer consideration by pharmacologists as a potential target in the mechanism of action of various psychoactive substances.

Velocity coding in the central brain of bumblebees.

Moving animals experience wide-field optic flow due to the displacement of the retinal image during motion. These cues provide information about self-motion and are important for flight control and stabilization, and for more complex tasks like path integration. While in honeybees and bumblebees the use of wide-field optic flow in behavioral tasks is well investigated, little is known about the underlying neuronal processing of these cues. Furthermore, there is a discrepancy between the temporal frequency tuning observed in most motion-sensitive neurons described so far from the optic lobe of insects and the velocity tuning that has been shown for many behaviors. Here we investigated response properties of motion-sensitive neurons in the central brain of bumblebees. Extracellular recordings allowed us to present a large number of stimuli to probe the spatiotemporal tuning of these neurons. We presented moving gratings that simulated either front-to-back or back-to-front optic flow and found three response types. Direction-selective responses of one of the groups matched those of TN-neurons, which provide optic flow information to the central complex, while the other groups contained neurons with purely excitatory responses that were either selective or non-selective for stimulus direction. Most recorded units showed velocity-coding properties at lower angular velocities, but showed spatial frequency dependent responses at higher velocities. Based on behavioral data, neuronal modelling work has previously predicted the existence of non direction-selective neurons with such properties. Our data now provides physiological evidence for these neurons and shows that neurons with TN-like properties exhibit a similar velocity-dependent coding.

A systematic review of progenitor survival and maturation in Parkinsonian models

Stem cell–based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source. Unlike current therapeutic options for patients, this approach has the potential to provide long-term stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients. The ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain. Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies, the aim of this systematic review was to assess these parameters in human stem cell–derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease. A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024. After screening, 76 articles were included in the analysis from which 178 separate transplant studies were identified. From these, graft survival could be assessed in 52 studies and differentiation in 129 studies. Overall, we found that graft survival ranged from &lt; 1% to 500% of cells transplanted, with a median of 51% of transplanted cells surviving in the brain; while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%. This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell–derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

Human single-neuron activity is modulated by intracranial theta burst stimulation of the basolateral amygdala.

Individual neurons in the human brain were responsive to theta burst stimulationBasolateral amygdala stimulation preferentially modulated neurons in the hippocampus, orbitofrontal cortex, and amygdalaNeurons modulated by stimulation tended to have greater baseline firing ratesDuration, onset, and valence of neuronal modulation were heterogeneous. Campbell et al. identify a subset of neurons in humans whose firing rate is modulated by intracranial theta burst stimulation of the basolateral amygdala. Location and baseline activity of detected neurons were associated with responsiveness to stimulation. These results provide a link between micro- and macroscale responses evoked by stimulation.

EPCO-28. UNVEILING INVASIVE MECHANISMS OF GLIOBLASTOMA CELLS THROUGH MULTIMODAL SINGLE-CELL SEQUENCING

Abstract Glioblastoma (GBM) is the most common malignancy of the central nervous system, characterized by a dismal prognosis and inevitable recurrence despite aggressive standard-of-care therapy. Extensive colonization of the surrounding brain parenchyma precludes complete surgical resection, posing a significant therapeutic challenge. While well-studied in model systems, the molecular features and epigenetic regulators of invasive GBM cells remain under-explored directly in clinical samples. To address this gap, we performed a multimodal single-cell sequencing characterization of GBM tumor samples from anatomically distinct regions collected using MRI guidance. Our results demonstrate an enrichment of progenitor-like (neural- and oligodendrocyte-like) malignant states and neurons at the tumor margins. In contrast, differentiated-like states and myeloid cells were more abundant in the tumor core. Peri-tumoral progenitor-like malignant states expressed a unique neuronal signature associated with synaptic signaling, neurogenesis, and Notch signaling. Further, the expression of this neuronal signature was correlated with increased invasiveness. Analysis of matched primary-recurrent GBM patient cohorts revealed an expansion of this neuronal activity program, which was associated with worse overall survival. Motifs of proneural transcription factors implicated in neuronal lineage differentiation were also found to be differentially accessible in progenitor-like malignant states marked by the neuronal invasive signature, potentially contributing to the remodeling of cell states at the invasive margin. Further, cell-cell interaction analysis predicted greater communication between neurons and peri-tumoral progenitor-like malignant states, mediated predominantly through neurexin-neuroligin trans-synaptic signaling, facilitating synaptogenesis and the integration of tumor cells into neural circuits. Altogether, these findings suggest a model in which GBM invasive cells communicate with normal brain neurons in peri-tumoral regions, exploiting neurodevelopmental pathways to facilitate invasion and potentially seed recurrence. Our characterization of invasive GBM cells provides insight into the mechanisms of brain invasion and highlights potential therapeutic vulnerabilities of malignant invasive cells. Understanding these mechanisms opens new avenues for targeted therapies aimed at curtailing the invasive and adaptive capabilities of GBM.

MicroRNA-24 therapeutic potentials in infarction, stroke, and diabetic complications.

The prevalence of cardiovascular events, stroke, and diabetes worldwide underscores the urgent need for effective and minimally invasive treatments. With nearly 20million annual casualties attributed to cardiovascular diseases and an estimated 463million people living with diabetes in 2022. Identifying promising therapeutic candidates is paramount. MicroRNAs, short nucleic acids involved in regulating gene expression, emerge as potential game-changers. Among these, microRNA-24 (miR-24), a hypoxia-sensitive player in endothelial vessels, has protective roles against diverse vascular complications. Following heart infarction and stroke, elevating miR-24 expression proves beneficial by mitigating oxidative stress, inflammation, and apoptosis while enhancing cell survival. It reduces cardiac fibrosis in heart disease, regulates aberrant angiogenesis in cerebral hemorrhagic strokes, and enhances the functionality of cardiomyocytes and brain neurons. In diabetic conditions, augmenting miR-24 expression mitigates complications. Further, being miR-24 also expressed by the skeletal muscle (i.e., myo-miR) in response to exercise, this miRNA may participate in the complex molecular network that systemically spreads the beneficial effects of physical exercise. This review provides a comprehensive vision of the molecular mechanisms underpinning the miR-24 protective effects, offering new insights into its therapeutic potential and proposing a novel avenue for medical intervention.

MECHANISMS OF STRUCTURAL FEATURES IN THE CEREBRAL CORTEX IN MODELS OF PREMATURE AGING OF NERVOUS TISSUE AFTER BACTERIAL LIPOPOLYSACCHARIDE

Introduction. Many chemical compounds affect brain neurons differently than other cell populations. This is provided by the protective potential of the blood-brain barrier (BBB). One of the compounds capable of passing through the BBB is bacterial lipopolysaccharide (LPS). It can cause irreversible morphological changes in the neurons of the cerebral cortex. The aim of the work is to study the mechanisms of neuronal damage and death. Material and methods. More than 50 sources for 15 past years were analyzed at PubMed and Elibrary databases. Results. Astrocytes recognize LPS due to toll-like receptors, and glial macrophages are also able to capture areas of the external bacterial membrane with LPS. However, variations in the dose of LPS, the method and frequency of its administration have different effects on the morphology of the cerebral cortex. In particular, it is relevant to study changes similar to those in aging and neurodegenerative processes. Conclusion. The review examines the structural changes of neurons and glia in the use of LPS in adult animals. The authors conclude that repeated systemic administration of non-septic doses of LPS is most suitable for modeling aging-like changes, but it is necessary to develop a standardized model of such administration.

The effect of Vagus nerve stimulation (VNS) on seizure control, cognitive function, and quality of life in individuals with drug-resistant epilepsy: A systematic review article.

To evaluate the effect of vagus nerve stimulation (VNS) on seizure control, cognitive functions, and quality of life in individuals with drug-resistant epilepsy. An extensive search of electronic databases was carried out in order to carry out this systematic review. The databases Google Scholar, Embase, PubMed, and the Cochrane Library were searched first to carryout gray literature. To reduce the quantity of pointless studies in the advanced search, the search is limited to "human studies" and "English language" publications only. Combining keywords and Medical Subject Headings (MeSH) terms like ("Vagus Nerve Stimulation" OR "VNS") AND ("Epilepsy" OR "Seizure Control") AND ("Cognitive Function" OR "Quality of Life"). Studies that have been published up to November 30/2023 were included. The search strategy yielded a total of 392 relevant studies. The mean age of participant's ranges from 11 years to 33 years. The duration of follow-up ranging from 6 to 36 months. Eleven studies were included in the review. The mean≥50% response rate after VNS therapy was 56.94% ranged from 48.90% to 83.00%. Four and three studies provided information about Quality of Life in Epilepsy Inventory (QOLIE-31) and The Liverpool Seizure Severity Scale (LSSS) questionnaires respectively. Epilepsy is a chronic disease characterized by sudden abnormal discharge of brain neurons, which leads to transient brain dysfunction and the presence of spontaneous recurrent seizures. Vagus nerve stimulation has recently been proposed as a potential tool in the treatment of seizure, depressive symptoms, and cognitive impairments. There has been variation in the effects of VNS treatment on seizure control, cognitive functions, and quality of life among patients with drug-resistant epilepsy. So, a comprehensive review of exciting literature is important to see the pooled effect. Previous systematic review and meta-analysis papers were mostly randomized control trial type with specific diseases. The use of a wider variety of study designs than only randomized controlled trials is important. So, we included retrospective and prospective cohort studies in addition to randomized control trials. This enables a more thorough assessment of the connection between quality of life, cognitive function, and vagus nerve stimulation. In addition, the paper looks at a wide range of disease kinds and patterns. We have established a uniform and comprehensive approach throughout the selected studies by mandating the inclusion of all three crucial parameters: vagus nerve stimulation, cognitive function, and quality of life. This systematic review examined 392 relevant studies on vagus nerve stimulation (VNS) therapy, with participants ranging from 11 to 33 years old and follow-up durations of 6-36 months. Eleven studies were included, and the mean response rate after VNS therapy was 56.94%, ranging from 48.90% to 83.00%. The review also reported on quality of life and cognitive function, and seizure severity frequency result from several studies.

Roasted Astragalus membranaceus Inhibits Aβ25-35-Induced Oxidative Stress in Neuronal Cells by Activating the Nrf2/HO-1 and AKT/CREB/BDNF Pathways.

(1) Background: Astragalus membranaceus (AM) has antioxidant and anti-inflammatory effects, but its specific mechanism of action in the brain is still unclear. In this study, we developed a roasting process to maximize the cognitive improvement impact of AM. We focused on enhancing physiological activity to enhance the brain neuron protection effect and alleviate neuronal damage caused by neurodegenerative diseases. (2) Methods: AM was roasted at 260 °C for 20, 30, or 40 min, and the hot water extracts were tested on HT22 cells for ROS levels, apoptosis, and antioxidant protein expression. The effect on the BDNF-AKT-CREB pathway under stress was also analyzed. (3) Results: Roasted AM decreased ROS production and the expression of apoptosis-related factors while activating the expression of antioxidant proteins in HT22 cells treated with Aβ25-35. In particular, 30 min roasting (R-AM2) significantly reduced ROS production, inhibited cell death, and increased antioxidant protein expression. The Nrf2 pathway was activated Bax, and cleaved caspase-3 levels were reduced. BDNF and p-CREB expression were increased by 20% and 50-70%, respectively. In the MAPK pathway, p-ERK levels were increased by 30%, and p-P38 levels were increased by approximately 20%. (4) Conclusions: These findings suggest that roasted AM upregulates brain-derived neurotrophic factor (BDNF) in HT22 cells, providing neuroprotective effects by activating the AKT/CREB/BDNF pathway and inhibiting neuronal apoptosis. Therefore, roasted AM shows potential as a neuroprotective agent for preventing or treating neurodegenerative diseases, such as Alzheimer's, linked to BDNF deficiency.