Synaptic Function Research Articles

Multidimensional free shape-morphing flexible neuromorphic devices with regulation at arbitrary points

Biological neural systems seamlessly integrate perception and action, a feat not efficiently replicated in current physically separated designs of neural-imitating electronics. This segregation hinders coordination and functionality within the neuromorphic system. Here, we present a flexible device tailored for neuromorphic computation and muscle actuation. Each individual device component emulates essential synaptic functions for neural computing, while the collective ensemble replicates muscle actuation in response to efferent neuromuscular commands. These properties stem from densely-packed, hydrophilic nanometer-sized channels, and the erection of a high-entropy, intricately silver nanowires to capture and store of hydrated cations. Leveraging the remarkable deformation effect, we demonstrate hazard detection-avoidance robot, and multidimensional integration for arbitrary programmed shapes like 360° panoramic information capture and soft-bodied biological deformations wherein localized responses to stimuli are harmoniously integrated to achieve arbitrary coordinated motion. These results provide a significant avenue for the development of future flexible electronics and bio-inspired systems.

Establishment and Validation of the Diagnostic Value of Oligodendrocyte-related Genes in Alzheimer's Disease.

AD is a demyelinating disease. Myelin damage initiates the pathological process of AD, resulting in abnormal synaptic function and cognitive decline. The myelin sheath formed by oligodendrocytes (OL) is a crucial component of white matter. Investigating AD from the perspective of OL may offer novel diagnostic and therapeutic perspectives. This study aimed to analyze the association between OL-related genes and Alzheimer's disease (AD) using bioinformatics and verify this association via molecular biology experiments. The AD datasets were acquired from the Gene Expression Omnibus (GEO) database of NCBI. Consensus clustering was employed to determine the subtypes of AD, followed by evaluating the clinical characteristics of these subtypes. Subsequently, immune infiltration analysis of relevant genes and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identify modules and hub genes associated with AD progression. The intersection of genes obtained was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. To narrow down the scope and identify OL-related genes with diagnostic potential, three machine learning algorithms were utilized. In addition, the eXtreme Sum (XSum) algorithm was used to screen small molecule drug candidates based on the connectivity map (CMAP) database. Finally, these identified genes were validated using Real-time fluorescence quantitative PCR (RT-qPCR). Among the three subtypes of AD, Cluster A and Cluster C exhibited increased levels of Braak and neurofibrillary tangles compared to Cluster B. The proportion of females was greater than that of males among the three subclasses of AD. There were no significant differences in age among the three subclasses, but significant differences in gene expression existed. Through WGCNA analysis, 108 genes were identified. Among these, 16 genes were identified as shared genes by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machines (SVM) algorithms, and logistic regression further determined 11 genes. The establishment of a nomogram demonstrated the significance of these 11 genes in AD. The "XSum" algorithm revealed five drugs with therapeutic potential for AD. qPCR analysis revealed the upregulation and downregulation of the highlighted genes. According to this study, 11 genes related to OL were also found to be associated with immune cell infiltration in AD patients. These genes demonstrated potential diagnostic value for AD. Additionally, we screened five small molecular drugs that exhibit potential therapeutic effects on AD. This research provides a new perspective for personalized clinical management and treatment of AD.

Cationic peptides cause memory loss through endophilin-mediated endocytosis.

The zeta inhibitory peptide (ZIP) interferes with memory maintenance and long-term potentiation (LTP)1 when administered to mice. However, mice lacking its putative target, protein kinase PKMζ, exhibit normal learning and memory as well as LTP2,3, making the mechanism of ZIP unclear. Here we show that ZIP disrupts LTP by removing surface AMPA receptors through its cationic charge alone. This effect requires endophilin-A2-mediated endocytosis and is fully blocked by drugs suppressing macropinocytosis. ZIP and other cationic peptides remove newly inserted AMPA receptor nanoclusters at potentiated synapses, providing a mechanism by which these peptides erase memories without altering basal synaptic function. When delivered in vivo, cationic peptides canmodulate memories on local and brain-wide scales, and these mechanisms can be leveraged to prevent memory loss in a model of traumatic brain injury. Our findings uncover a previously unknown synaptic mechanism by which memories are maintained or lost.

Changes in RNA Splicing: A New Paradigm of Transcriptional Responses to Probiotic Action in the Mammalian Brain

Elucidating the gene regulatory mechanisms underlying the gut–brain axis is critical for uncovering novel gut–brain interaction pathways and developing therapeutic strategies for gut bacteria-associated neurological disorders. Most studies have primarily investigated how gut bacteria modulate host epigenetics and gene expression; their impact on host alternative splicing, particularly in the brain, remains largely unexplored. Here, we investigated the effects of the gut-associated probiotic Lacidofil® on alternative splicing across 10 regions of the rat brain using published RNA-sequencing data. The Lacidofil® altogether altered 2941 differential splicing events, predominantly, skipped exon (SE) and mutually exclusive exon (MXE) events. Protein–protein interactions and a KEGG analysis of differentially spliced genes (DSGs) revealed consistent enrichment in the spliceosome and vesicle transport complexes, as well as in pathways related to neurodegenerative diseases, synaptic function and plasticity, and substance addiction across brain regions. Using the PsyGeNET platform, we found that DSGs from the locus coeruleus (LConly), medial preoptic area (mPOA), and ventral dentate gyrus (venDG) were enriched in depression-associated or schizophrenia-associated genes. Notably, we highlight the App gene, where Lacidofil® precisely regulated the splicing of two exons causally involved in amyloid β protein-based neurodegenerative diseases. Although the splicing factors exhibited both splicing plasticity and expression plasticity in response to Lacidofil®, the overlap between DSGs and differentially expressed genes (DEGs) in most brain regions was rather low. Our study provides novel mechanistic insight into how gut probiotics might influence brain function through the modulation of RNA splicing.

MiRNAs as major players in brain health and disease: current knowledge and future perspectives.

MicroRNAs are regulators of gene expression and their dysregulation can lead to various diseases. MicroRNA-135 (MiR-135) exhibits brain-specific expression, and performs various functions such as neuronal morphology, neural induction, and synaptic function in the human brain. Dysfunction of miR-135 has been reported in brain tumors, and neurodegenerative and neurodevelopmental disorders. Several reports show downregulation of miR-135 in glioblastoma, indicating its tumor suppressor role in the pathogenesis of brain tumors. In this review, by performing in silico analysis of molecular targets of miR-135, we reveal the significant pathways and processes modulated by miR-135. We summarize the biological significance, roles, and signaling pathways of miRNAs in general, with a focus on miR-135 in different neurological diseases including brain tumors, and neurodegenerative and neurodevelopmental disorders. We also discuss methods, limitations, and potential of glioblastoma organoids in recapitulating disease initiation and progression. We highlight the promising therapeutic potential of miRNAs as antitumor agents for aggressive human brain tumors including glioblastoma.

Cell Membrane-Integrated Neuroligin-1 Regulates the Anti-Inflammatory Effects of CRC Cell-Derived Exosomes

Tumor-associated macrophages (TAMs) are one of the most abundant cell types in the colorectal cancer (CRC) tumor microenvironment (TME). CRC cell-derived exosomes support macrophage polarization toward an M2-like phenotype, which leads to tumor growth and metastasis. Neuroligin 1 (NLG1) is a transmembrane protein critical in synaptic function. We reported that NLG1 via an autocrine manner promotes CRC progression by modulating the APC/β-catenin pathway. This study aimed to answer whether NLG1 is involved in the exosome-mediated intercellular cross-talk between CRC and TAMs. Our results showed that exosomes of NLG1-expressing CRC cells induce M2-like (CD206high CD80low) polarization in macrophages. On the other hand, we found that the exosomes of the NLG1 knocked-down CRC cells reinforce the expression of CD80 and pro-inflammatory genes, including IL8, IL1β, and TNFα, in the macrophages, indicating an M1-like phenotype polarization. In conclusion, NLG1, as a cell-membrane-integrated protein, could be a therapeutic target on the surface of the CRC cells for developing clinical treatments to inhibit exosome-induced anti-inflammatory immune responses in TME.

Transcriptomic Analysis of Effects of Developmental PCB Exposure in the Hypothalamus of Female Rats.

This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these phenotypes. We used 3' targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.

Amyloid-β-driven synaptic deficits are mediated by synaptic removal of GluA3-containing AMPA-receptors.

The detrimental effects of oligomeric amyloid-β (Aβ) on synapses are considered the leading cause for cognitive deficits in Alzheimer's disease. However, through which mechanism Aβ oligomers impair synaptic structure and function remains unknown. Here, we used electrophysiology and AMPA-receptor (AMPAR) imaging on mice and rat neurons to demonstrate that GluA3 expression in neurons lacking GluA3 is sufficient to re-sensitize their synapses to the damaging effects of Aβ, indicating that GluA3-containing AMPARs at synapses are necessary and sufficient for Aβ to induce synaptic deficits. We found that Aβ-oligomers trigger the endocytosis of GluA3 and promote its translocation towards endo-lysosomal compartments for degradation. Mechanistically, these Aβ-driven effects critically depend on the PDZ-binding motif of GluA3. A single point mutation in the GluA3 PDZ-binding motif prevented Aβ-driven effects and rendered synapses fully resistant to the effects of Aβ. Correspondingly, proteomics on synaptosome fractions from APP/PS1-transgenic mice revealed a selective reduction of GluA3 at an early age. These findings support a model where the endocytosis and lysosomal degradation of GluA3-containing AMPARs is a critical early step in the cascade of events through which Aβ accumulation causes a loss of synapses.Significance statement Early cognitive symptoms in Alzheimer's disease are considered to be driven by dysfunctional synapses. Studies in animal models for Alzheimer's disease have demonstrated that the preservation of synapses alleviates cognitive symptoms. However, a clinically viable approach to preserve synapses requires a mechanistic understanding of how synaptic function is perturbed. Our study reveals that synapse impairments in Alzheimer models require the synaptic removal and subsequent lysosomal degradation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that contain subunit GluA3. Preventing this aberrant trafficking of GluA3 leads to the preservation of synapses. This study identifies that the presence of GluA3 determines whether synapses are vulnerable to Alzheimer pathology, thereby deepening our understanding of how synapses are affected in Alzheimer's disease.

Q241R mutation of Braf causes neurological abnormalities in a mouse model of cardio-facio-cutaneous syndrome, independent of developmental malformations.

Constitutively active mutants of BRAF cause cardio-facio-cutaneous (CFC) syndrome, characterized by growth and developmental defects, cardiac malformations, facial features, cutaneous manifestations, and mental retardation. An animal model of human CFC syndrome, the systemic BrafQ241R/+ mutant mouse, has been reported to exhibit multiple CFC syndrome-like phenotypes. In this study, we analyzed the effects of Braf mutations on neural function, separately from their effects on developmental processes. To this end, we generated Braf mutant mice expressing BRAFQ241R specifically in mature excitatory neurons (n-BrafQ241R/+). We found no growth retardation or cardiac malformations in n-BrafQ241R/+ mice, indicating normal development. Behavioral analysis revealed that n-BrafQ241R/+ mice exhibited reduced home cage activity and learning disability, which were similar to those of systemic BrafQ241R/+ mice. The active form of ERK was increased in the hippocampus of n-BrafQ241R/+ mice, whereas basal synaptic transmission and synaptic plasticity in hippocampal Schaffer collateral-CA1 synapses seems to be normal. Transcriptome analysis of the hippocampal tissue revealed significant changes in the expression of genes involved in regulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway, synaptic function and memory formation. These data suggest that the neuronal dysfunction observed in the systemic CFC mouse model is due to the disruption of homeostasis of the RAS/MAPK signaling pathway by the activated Braf mutant after maturation, rather than abnormal development of the brain. A similar mechanism may be possible in human CFC syndrome.

BK channels mediate a presynaptic form of mGluR-LTD in the neonatal hippocampus

BK channels can control neuronal function, but their functional relevance in activity-dependent changes of synaptic function remains elusive. Here, we report that repetitive low-frequency stimulation activates BK channels through 12(S)HPETE, an arachidonic acid metabolite, produced downstream of postsynaptic metabotropic glutamate receptors (mGluRs) to trigger long-term depression (LTD) at CA3-CA1 synapses in hippocampal slices from P7-P10 mice. Activation of BK channels is subunit specific, as paxilline but not iberiotoxin blocked mGluR-LTD. Also, 12(S)HPETE does not change the electrophysiological properties of the BK channel when the BKα subunit is expressed alone but increases the channel open probability when the BKα is coexpressed with the β4-subunit. Our findings reveal an interaction between 12(S)HPETE and BK channels to regulate synaptic strength at central synapses and increase our understanding of the mechanisms underlying mGluR-LTD in the neonatal hippocampus that likely contribute to circuit maturation necessary for learning.

Fetal growth restriction adversely impacts trajectory of hippocampal neurodevelopment and function.

The last pregnancy trimester is critical for fetal brain development but is a vulnerable period if the pregnancy is compromised by fetal growth restriction (FGR). The impact of FGR on the maturational development of neuronal morphology is not known, however, studies in fetal sheep allow longitudinal analysis in a long gestation species. Here we compared hippocampal neuron dendritogenesis in FGR and control fetal sheep at three timepoints equivalent to the third trimester of pregnancy, complemented by magnetic resonance image for brain volume, and electrophysiology for synaptic function. We hypothesized that the trajectory of hippocampal neuronal dendrite outgrowth would be decreased in the growth-restricted fetus, with implications for hippocampal volume, connectivity, and function. In control animals, total dendrite length increased with advancing gestation, but not in FGR, resulting in a significantly reduced trajectory of dendrite outgrowth in FGR fetuses for total length, branching, and complexity. Ex vivo electrophysiology analysis shows that paired-pulse facilitation was reduced in FGR compared to controls for cornu ammonis 1 hippocampal outputs, reflecting synaptic dysfunction. Hippocampal brain-derived neurotrophic factor density decreased over late gestation in FGR fetuses but not in controls. This study reveals that FGR is associated with a significant deviation in the trajectory of dendrite outgrowth of hippocampal neurons. Where dendrite length significantly increased over the third trimester of pregnancy in control brains, there was no corresponding increase over time in FGR brains, and the trajectory of dendrite outgrowth in FGR offspring was significantly reduced compared to controls. Reduced hippocampal dendritogenesis in FGR offspring has severe implications for the development of hippocampal connectivity and long-term function.

Neurotrophomodulatory effect of TNF-α through NF-κB in rat cortical astrocytes.

Tumor necrosis factor alpha (TNF-α) is a well-known pro-inflammatory cytokine originally recognized for its ability to induce apoptosis and cell death. However, recent research has revealed that TNF-α also plays a crucial role as a mediator of cell survival, influencing a wide range of cellular functions. The signaling of TNF-α is mediated through two distinct receptors, TNFR1 and TNFR2, which trigger various intracellular pathways, including NF-κB, JNK, and caspase signaling cascades. Both TNFR1 and TNFR2 are expressed in astrocytes, which are specialized glial cells essential for maintaining the structural and functional integrity of the central nervous system (CNS). Astrocytes support neuronal function by regulating brain homeostasis, maintaining synaptic function, and supplying metabolic substrates. In addition, astrocytes are known to secrete a variety of growth factors and neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4/5. These neurotrophins play a critical role in supporting neuronal survival, synaptic plasticity, and myelination within the brain. The present study focuses on the role of TNF-α in modulating neurotrophin expression and secretion in rat cortical astrocytes. We demonstrate that TNF-α induces the upregulation of neurotrophins, particularly NGF and BDNF, in cultured astrocytes. This effect is accompanied by an increase in the expression of their respective receptors (TrkA & TrkB), further suggesting a functional modulation of neurotrophic signaling pathways. Notably, we show that the modulation of neurotrophin expression by TNF-α is mediated via the NF-κB signaling pathway. Additionally, we observed that TNF-α also regulates the secretion levels of NGF and BDNF into the culture media of astrocytes in a dose-dependent manner, indicating that TNF-α can modulate both the production and release of these growth factors. Taken together, our findings highlight a previously underexplored neuroprotective role of TNF-α in astrocytes. Specifically, we propose that TNF-α, through the upregulation of neurotrophins, may contribute to maintaining neuronal health and supporting neuroprotection under disease conditions.

The Role of Glial Cells in Autism Spectrum Disorder: Molecular Mechanisms and Therapeutic Approaches.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Emerging evidence highlights the significant role of glial cells, particularly astrocytes and microglia, in the pathophysiology of ASD. Glial cells are crucial for maintaining homeostasis, modulating synaptic function, and responding to neural injury. Dysregulation of glial cell functions, including altered cytokine production, impaired synaptic pruning, and disrupted neuroinflammatory responses, has been implicated in ASD. Molecular mechanisms underlying these disruptions involve aberrant signaling pathways, such as the mTOR pathway, and epigenetic modifications, leading to altered gene expression profiles in glial cells. Moreover, microglial activation and reactive astrocytosis contribute to an inflammatory environment that exacerbates neural circuit abnormalities. Understanding these molecular mechanisms opens avenues for therapeutic interventions. Current therapeutic approaches targeting glial cell dysfunction include anti-inflammatory agents, modulators of synaptic function, and cell-based therapies. Minocycline and ibudilast have shown potential for modulating microglial activity and reducing neuroinflammation. Additionally, advancements in gene editing and stem cell therapy hold promise for restoring normal glial function. This abstract underscores the importance of glial cells in ASD. It highlights the need for further research to elucidate the complex interactions between glial dysfunction and ASD pathogenesis, aiming to develop targeted therapies that can ameliorate the clinical manifestations of ASD.

Subchronic cyanuric acid treatment impairs spatial flexible behavior in female adolescent rats through depressing GluN2B-dependent neuronal and synaptic function.

Subchronic exposure to cyanuric acid (CA) and its structural analogue melamine induces long-term effects on brain and behavior in male rodents. To examine if this exposure induced negative effects on cognitive function in females, we examined the behavioral performance and further attempted to investigate synaptic and neuronal function. CA was intraperitoneal treated with 20 or 40 mg/kg/day to adolescent female rats for 4 consecutive weeks. Multiple behavioral tests were employed to assess spatial cognition, learning strategy, locomotion and motivation. Hippocampal synaptic function at Schaffer collaterals-CA1 synapses and excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons was evaluated. Meanwhile, the glutamate transport inhibitor DL-threo-β-benzyloxyaspartate (DL-TBOA) was infused into hippocampal CA1 region to certify the underlying mechanism. We found that subchronic CA exposure impairs reversal learning ability with dose-dependent effects but did not affect spatial learning and memory, or learning strategy. The expression and phosphorylation of N-methyl-D-aspartate receptor (NMDAR) GluN2B subunits were simultaneously reduced in the hippocampus and the GluN2B-mediated synaptic function, including long-term depression (LTD) and paired-pulse facilitation (PPF), was suppressed. CA could also diminish postsynaptic density protein-95 (PSD-95) expression but did change the levels of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) GluA1 or NMDAR GluN2A subunit, or hippocampal spine density. Meanwhile, CA depressed frequency and amplitude of GluN2B-mediated EPSCs, indicating the presynaptic and postsynaptic actions of CA on neuronal activity. Furthermore, the DL-TBOA infusions could effectively mitigate the diminished GluN2B-LTD and GluN2B-EPSCs and the impairments in behavioral flexibility. Our findings provide the first evidence that CA can exert neurotoxic effects on females and certify that one of the potential mechanisms for neuronal and synaptic dysfunction is the GluN2B-mediated signaling pathway.

Deep proteomics and network pharmacology reveal sex- and age-shared neuropathic pain signatures in mouse dorsal root ganglia.

Our understanding of how sex and age influence chronic pain at the molecular level is still limited with wide-reaching consequences for adolescent patients. Here, we leveraged deep proteome profiling of mouse dorsal root ganglia (DRG) from adolescent (4-week-old) and adult (12-week-old) male and female mice to investigate the establishment of neuropathic pain in the spared nerve injury (SNI)-model in parallel. We quantified over 12,000 proteins, including notable ion channels involved in pain, highlighting the sensitivity of our approach. Differential expression revealed sex- and age-dependent proteome changes upon nerve injury. In contrast to most previous studies, our comprehensive dataset enabled us to determine differentially expressed proteins (DEPs), which were shared between male and female mice of both age groups. Among these, the vast majority (94 %) were also expressed and, in part, altered in human DRG of neuropathic pain patients, indicating evolutionary conservation. Proteome signatures represented numerous targets of FDA-approved drugs comprising both (i) known pain therapeutics (e.g. Pregabalin and opioids) and, importantly, (ii) compounds with high potential for future re-purposing, e.g. Ptprc-modulators and Epoetins. Protein network and multidimensional analysis uncovered distinct hubs of sex- and age-shared biological pathways impacted by neuropathic pain, such as neuronal activity and synaptic function, DNA-damage, and neuroimmune interactions. Taken together, our results capture the complexity of nerve injury-associated DRG alterations in mice at the network level, moving beyond single-candidate studies. Consequently, we provide an innovative resource of the molecular landscape of neuropathic pain, enabling novel opportunities for translational pain research and network-based drug discovery.

A triradical-containing trinuclear Pd(II) complex: spin-polarized electronic transmission, analog resistive switching and neuromorphic advancements.

Neuromorphic computation has emerged as a potential alternative to subvert the von Neumann bottleneck issue in conventional computing. In this context, the development of resistive switching-based memristor devices mimicking various synaptic functionalities has engendered paramount attention. Here, we report a triradical-containing trinuclear Pd(II) cluster with a cyclohexane-like framework constituted by the Pd-Se coordination motif displaying facile memristor property with neuromorphic functionality as a thin-film device. The metal-ligand complex (complex 1) possessed an St = 1/2 ground state by experiencing a spin-frustrated-type magnetic coupling phenomenon amongst the three ligand-based organic radicals (SR = 1/2), coordinated to the Pd(II) ions. Three reversible one-electron reduction waves countered with a one-electron and one two-electron reversible oxidation waves were noticed in the cyclic voltammogram of the complex, confirming electrons accepting and releasing capacity of the complex at low potentials, i.e., within +0.2 V to -1.1 V. Employing the radical-containing complex 1 as the active thin-film sandwiched between two orthogonal electrodes, resistive switching based memristor property with biological synaptic actions were successfully emulated. Intriguingly, the artificial neural network (ANN) simulated efficient pattern recognition demonstrated using the recorded potentiation and depression curves from the device, which is a step ahead for the hardware realization of neuromorphic computing. The performance of the ANN on MNIST data with reduced image resolution has further been evaluated. Density functional theory (DFT)-based theoretical calculation predicted that the spin-polarized electronic transmission substantiated the memristive property in the neutral complex 1.

Indirect influence on the BDNF/TrkB receptor signaling pathway via GPCRs, an emerging strategy in the treatment of neurodegenerative disorders.

Neuronal survival depends on neurotrophins and their receptors. There are two types of neurotrophin receptors: a nonenzymatic, trans-membrane protein of the tumor necrosis factor receptor (TNFR) family-p75 receptor and the tyrosine kinase receptors (TrkR) A, B, and C. Activation of the TrkBR by brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5) promotes neuronal survival, differentiation, and synaptic function. It is shown that in the pathogenesis of several neurodegenerative conditions (Alzheimer's disease, Parkinson's disease, Huntington's disease) the BDNF/TrkBR signaling pathway is impaired. Since it is known that GPCRs and TrkR are regulating several cell functions by interacting with each other and generating a cross-communication in this review we have focused on the interaction between different GPCRs and their ligands on BDNF/TrkBR signaling pathway.

Gut microbiota may affect Alzheimer's disease through synaptic function mediated by CAMs pathway: A study combining Mendelian randomization and bioinformatics

Background The association between gut microbes and Alzheimer's disease (AD) has not been entirely elucidated. Objective We aimed to demonstrate the association between gut microbes and AD and to further investigate the pathogenesis of microbes with a causal relationship to AD. Methods Mendelian randomization analyses were used to determine the significant causal relationship between gut microbes and AD. Protein-protein interaction (PPI) network was used to identify the hub genes. Functional enrichment analysis was used to reveal the pathogenesis theoretically between gut microbes and AD. Results In the present study, a total of 32 microbes were identified that were significantly associated with AD. Subsequently, DLGAP2, NRXN3, NEGR1, NTNAP2, MYH9, and SCN3A were identified as hub genes. The genes NRXN3, NEGR1, and NTNAP2 were enriched in the cell adhesion molecules (CAMs) signaling, and the taxons of gut microbes that corresponded to these were Bifidobacterium adolescentis, Actinomycetales, and Intestinimonas massiliensis. Conclusions Bifidobacterium adolescentis, Actinomycetales, and Intestinimonas massiliensis may promote the progression of AD through the regulation of the CAMs signaling pathway-mediated synaptic function. Hence, the in-depth study of gut microbes may increase the efficiency of screening and diagnosis of AD.

Oxide-based bionic hetero-dendritic neuron with capabilities of Bienenstock–Cooper–Munro learning activities

A multi-gate sodium alginate/graphene oxide gated oxide hetero-dendritic neuron was proposed, demonstrating high-pass filter characteristics and BCM learning rules under the spike-timing-dependent plasticity and heterosynaptic mechanism.

Lipids shape brain function through ion channel and receptor modulations: physiological mechanisms and clinical perspectives.

Lipids represent the most abundant molecular type in the brain, with a fat content of ∼60% of the dry brain weight in humans. Despite this fact, little attention has been paid to circumscribe the dynamic role of lipids in brain function and disease. Membrane lipids such as cholesterol, phosphoinositide, sphingolipids, arachidonic acid, and endocannabinoids finely regulate both synaptic receptors and ion channels that ensure critical neural functions. After a brief introduction on brain lipids and their respective properties, we review here their role in regulating synaptic function and ion channel activity, action potential propagation, neuronal development, and functional plasticity and their contribution in the development of neurological and neuropsychiatric diseases. We also provide possible directions for future research on lipid function in brain plasticity and diseases.