Molecular Brain最新文献

{"title":"Synthetic data-driven overlapped neural spikes sorting: decomposing hidden spikes from overlapping spikes.","authors":"Min-Ki Kim, Sung-Phil Kim, Jeong-Woo Sohn","doi":"10.1186/s13041-024-01161-y","DOIUrl":"https://doi.org/10.1186/s13041-024-01161-y","url":null,"abstract":"<p><p>Sorting spikes from extracellular recordings, obtained by sensing neuronal activity around an electrode tip, is essential for unravelling the complexities of neural coding and its implications across diverse neuroscientific disciplines. However, the presence of overlapping spikes, originating from neurons firing simultaneously or within a short delay, has been overlooked because of the difficulty in identifying individual neurons due to the lack of ground truth. In this study, we propose a method to identify overlapping spikes in extracellular recordings and to recover hidden spikes by decomposing them. We initially estimate spike waveform templates through a series of steps, including discriminative subspace learning and the isolation forest algorithm. By leveraging these estimated templates, we generate synthetic spikes and train a classifier using their feature components to identify overlapping spikes from observed spike data. The identified overlapping spikes are then decomposed into individual hidden spikes using a particle swarm optimization. Results from the testing of the proposed approach, using the simulation dataset we generated, demonstrated that employing synthetic spikes in the overlapping spike classifier accurately identifies overlapping spikes among the detected ones (the maximum F1 score of 0.88). Additionally, the approach can infer the synchronization between hidden spikes by decomposing the overlapped spikes and reallocating them into distinct clusters. This study advances spike sorting by accurately identifying overlapping spikes, providing a more precise tool for neural activity analysis.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"89"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histamine H₃ receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization during resting state: an exploratory cortex-wide imaging study in mice.","authors":"Sentaro Kaita, Yoshikazu Morishita, Kenta Kobayashi, Hiroshi Nomura","doi":"10.1186/s13041-024-01165-8","DOIUrl":"https://doi.org/10.1186/s13041-024-01165-8","url":null,"abstract":"<p><p>The histaminergic system plays a key role in modulating learning and memory, wakefulness, and energy balance. Histamine H₃ receptors constitutively inhibit the synthesis and release of histamine and other neurotransmitters. Therefore, H₃ receptor inverse agonists/antagonists increase the synthesis and release of these neurotransmitters, enhancing cognitive functions, including memory consolidation and retrieval. Spontaneous neural activity across the cerebral cortex is essential for cognitive function, including memory consolidation. Abnormal spontaneous activity has, in fact, been associated with cognitive dysfunctions and psychiatric disorders. Given the cognitive improvement achieved with the use of H₃ receptor inverse agonists/antagonists, we examined the effects of two inverse agonists/antagonists - thioperamide and pitolisant - on spontaneous cortical activity, using in vivo wide-field Ca²⁺ imaging. Changes in cortical activity, across multiple cortical regions and in inter-regional connectivity, from pre- to post-administration were evaluated using a linear support vector machine decoder. Thioperamide and pitolisant both modified the amplitude distribution of calcium events across multiple cortical regions, including a reduction in the frequency of low-amplitude calcium events in the somatosensory cortex. Graph theory analysis revealed increases in centrality measures in the somatosensory cortex with the use of both thioperamide and pitolisant, indicative of their importance in the organization of cortical networks. These findings indicate that H₃ receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization of activity in the cerebral cortex during the resting state.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"88"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcutaneous auricular vagus nerve stimulation in anesthetized mice induces antidepressant effects by activating dopaminergic neurons in the ventral tegmental area.","authors":"Tae-Yong Choi, Jeongseop Kim, Ja Wook Koo","doi":"10.1186/s13041-024-01162-x","DOIUrl":"https://doi.org/10.1186/s13041-024-01162-x","url":null,"abstract":"<p><p>Depression, a prevalent neuropsychiatric disorder, involves the dysregulation of neurotransmitters such as dopamine (DA). The restoration of DA balance is a pivotal therapeutic target for this condition. Recent studies have indicated that both antidepressant medications and non-pharmacological treatments, such as transcutaneous auricular vagus nerve stimulation (taVNS), can promote recovery from depressive symptoms. Despite the promise of taVNS as a non-invasive depression therapy, its precise mechanism remains unclear. We hypothesized that taVNS exerts antidepressant effects by modulating the DAergic system. To investigate this, we conducted experiments demonstrating that taVNS in anesthetized mice reduced depressive-like behaviors. However, this effect was abolished when DA neurons in the ventral tegmental area (VTA^DA) were inhibited. Additionally, taVNS in anesthetized mice enhanced VTA^DA activity, providing further evidence to support its antidepressant effects. Overall, our findings suggest that taVNS alleviates depression by augmenting VTA^DA activity, thereby contributing to a more comprehensive understanding of its therapeutic mechanisms.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"86"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism.","authors":"Ozan Baytas, Shawn M Davidson, Julie A Kauer, Eric M Morrow","doi":"10.1186/s13041-024-01154-x","DOIUrl":"https://doi.org/10.1186/s13041-024-01154-x","url":null,"abstract":"<p><p>Recessive loss-of-function mutations in the mitochondrial enzyme Glutamate Pyruvate Transaminase 2 (GPT2) cause intellectual disability in children. Given this cognitive disorder, and because glutamate metabolism is tightly regulated to sustain excitatory neurotransmission, here we investigate the role of GPT2 in synaptic function. GPT2 catalyzes a reversible reaction interconverting glutamate and pyruvate with alanine and alpha-ketoglutarate, a TCA cycle intermediate; thereby, GPT2 may play an important role in linking mitochondrial tricarboxylic acid (TCA) cycle with synaptic transmission. In mouse brain, we find that GPT2 is enriched in mitochondria of synaptosomes (isolated synaptic terminals). Loss of Gpt2 in mouse appears to lead to reprogramming of glutamate and glutamine metabolism, and to decreased glutamatergic synaptic transmission. Whole-cell patch-clamp recordings in pyramidal neurons of CA1 hippocampal slices from Gpt2-null mice reveal decreased excitatory post-synaptic currents (mEPSCs) without changes in mEPSC frequency, or importantly, changes in inhibitory post-synaptic currents (mIPSCs). Additional evidence of defective glutamate release included reduced levels of glutamate released from Gpt2-null synaptosomes measured biochemically. Glutamate release from synaptosomes was rescued to wild-type levels by alpha-ketoglutarate supplementation. Additionally, we observed evidence of altered metabolism in isolated Gpt2-null synaptosomes: decreased TCA cycle intermediates, and increased glutamate dehydrogenase activity. Notably, alterations in the TCA cycle and the glutamine pool were alleviated by alpha-ketoglutarate supplementation. In conclusion, our data support a model whereby GPT2 mitochondrial activity may contribute to glutamate availability in pre-synaptic terminals, thereby highlighting potential interactions between pre-synaptic mitochondrial metabolism and synaptic transmission.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"87"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AKAP6 controls NFATc4 activity for BDNF-mediated neuroprotection.","authors":"Joanna Mackiewicz, Julia Tomczak, Malwina Lisek, Feng Guo, Tomasz Boczek","doi":"10.1186/s13041-024-01157-8","DOIUrl":"10.1186/s13041-024-01157-8","url":null,"abstract":"<p><p>Brain-derived neurotrophic factor (BDNF) is known for its potent prosurvival effect. Despite successfully replicating this effect in various clinical and pre-clinical models, the complete characterization of the molecular mechanisms underlying its neuroprotective action remains incomplete. Emerging research suggests a vital role for A-kinase anchoring proteins (AKAPs) as central nodal points orchestrating BDNF-dependent signaling. Among the over 50 identified AKAPs, AKAP6 has recently gained special attention due to its involvement in the neurotrophin-mediated survival of injured retinal ganglion cells (RGCs). However, the mechanisms by which AKAP6 responds to pro-survival BDNF signaling remain unknown. In this study, we shown that AKAP6 plays a crucial role in regulating BDNF-mediated NFAT transcriptional activity in neuronal survival by anchoring protein phosphatase calcineurin (CaN) and nuclear factor of activated T cells (NFATc4). Furthermore, we demonstrate that disrupting the anchoring of CaN diminishes the pro-survival effect of BDNF. Lastly, through experiments with NFATc4-/- mice, we provide evidence that NFATc4 acts downstream to BDNF's neuroprotection in vivo. These findings could offer valuable insights for developing neuroprotective strategies aimed at preserving injured neurons from degeneration and promoting their regeneration.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"85"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma.","authors":"Anne Rombaut, Rune Brautaset, Pete A Williams, James R Tribble","doi":"10.1186/s13041-024-01160-z","DOIUrl":"10.1186/s13041-024-01160-z","url":null,"abstract":"<p><p>Neuroinflammation is a significant contributor to the pathology of glaucoma. Targeting key-mediators in this process is a realistic option to slow disease progression. Galectin-3 is a β-galactoside binding lectin that has been associated with inflammation in both systemic and central nervous system diseases. Elevated Galectin-3 has recently been detected in multiple animal models of glaucoma and inhibiting Galectin-3 using an intravitreal injection of TD139 (a Galectin-3 small molecule inhibitor) is neuroprotective. We queried whether this neuroprotective effect was translatable to another animal model and species. TD139 was intravitreally injected, in a rat ocular hypertensive model of glaucoma, 3 days after the induction of ocular hypertension (at peak intraocular pressure). Retinal ganglion cell survival and glial morphological markers were quantified. The degeneration of retinal ganglion cells was prevented by TD139 injection, but gross glial markers remained unaffected. These data confirm that the intravitreal injection of TD139 is neuroprotective in a rat ocular hypertensive model of glaucoma, while suggesting that the inhibition of Galectin-3 is not sufficient to alter the gross inflammatory outcome.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"84"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A structural analysis of the splice-specific functional impact of the pathogenic familial hemiplegic migraine type 1 S218L mutation on Ca_v2.1 P/Q-type channel gating.","authors":"Anne-Sophie Sack, Gennerick J Samera, Anna Hissen, Robert J Wester, Esperanza Garcia, Paul J Adams, Terrance P Snutch","doi":"10.1186/s13041-024-01152-z","DOIUrl":"10.1186/s13041-024-01152-z","url":null,"abstract":"<p><p>P/Q-type (Ca_v2.1) calcium channels mediate Ca²⁺ influx essential for neuronal excitability and synaptic transmission. The CACNA1A gene, encoding the Ca_v2.1 pore forming subunit, is highly expressed throughout the mammalian central nervous system. Alternative splicing of Ca_v2.1 pre-mRNA generates diverse channel isoforms with distinct biophysical properties and drug affinities, which are differentially expressed in nerve tissues. Splicing variants can also affect channel function under pathological conditions although their phenotypic implication concerning inherited neurological disorders linked to CACNA1A mutations remains unknown. Here, we quantified the expression of Ca_v2.1 exon 24 (e24) spliced transcripts in human nervous system samples, finding different levels of expression within discrete regions. The corresponding Ca_v2.1 variants, differing by the presence (+) or absence (Δ) of Ser-Ser-Thr-Arg residues (SSTR) in the domain III S3-S4 linker, were functionally characterized using patch clamp recordings. Further, the + /ΔSSTR isoforms were used to demonstrate the differential impact of the Familial Hemiplegic Migraine Type 1 (FHM-1) S218L mutation, located in the domain I S4-S5 linker, on the molecular structure and electrophysiological properties of Ca_v2.1 isoforms. S218L has a prominent effect on the voltage-dependence of activation of +SSTR channels when compared to ΔSSTR, indicating a differential effect of the mutation depending on splice-variant context. Structural modeling based upon Cav2.1 cryo-EM data provided further insight reflecting independent contributions of amino acids in distant regions of the channel on gating properties. Our modelling indicates that by increasing hydrophobicity the Leu218 mutation contributes to stabilizing a structural conformation in which the domain I S4-S5 linker is oriented alongside the inner plasma membrane, similar to that occurring when S4 is translocated upon activation.The SSTR insertion appears to exert an influence in the local electric field of domain III due to an change in the distribution of positively charged regions surrounding the voltage sensing domain, which we hypothesize impacts its movement during the transition to the open state. In summary, we reveal molecular changes correlated with distinct functional effects provoked by S218L FHM-1 mutation in hCa_v2.1 splice isoforms whose differential expression could impact the manifestation of the neurological disorder.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"82"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.","authors":"Andrew Awuah Wireko, Adam Ben-Jaafar, Jonathan Sing Huk Kong, Krishitha Meenu Mannan, Vivek Sanker, Sophie-Liliane Rosenke, Allswell Naa Adjeley Boye, Princess Afia Nkrumah-Boateng, Jeisun Poornaselvan, Muhammad Hamza Shah, Toufik Abdul-Rahman, Oday Atallah","doi":"10.1186/s13041-024-01155-w","DOIUrl":"10.1186/s13041-024-01155-w","url":null,"abstract":"<p><p>CNS tumours encompass a diverse group of neoplasms with significant morbidity and mortality. The SHH signalling pathway plays a critical role in the pathogenesis of several CNS tumours, including gliomas, medulloblastomas and others. By influencing cellular proliferation, differentiation and migration in CNS tumours, the SHH pathway has emerged as a promising target for therapeutic intervention. Current strategies such as vismodegib and sonidegib have shown efficacy in targeting SHH pathway activation. However, challenges such as resistance mechanisms and paradoxical effects observed in clinical settings underscore the complexity of effectively targeting this pathway. Advances in gene editing technologies, particularly CRISPR/Cas9, have provided valuable tools for studying SHH pathway biology, validating therapeutic targets and exploring novel treatment modalities. These innovations have paved the way for a better understanding of pathway dynamics and the development of more precise therapeutic interventions. In addition, the identification and validation of biomarkers of SHH pathway activation are critical to guide clinical decision making and improve patient outcomes. Molecular profiling and biomarker discovery efforts are critical steps towards personalised medicine approaches in the treatment of SHH pathway-associated CNS tumours. While significant progress has been made in understanding the role of the SHH pathway in CNS tumorigenesis, ongoing research is essential to overcome current therapeutic challenges and refine treatment strategies. The integration of molecular insights with advanced technologies and clinical expertise holds great promise for developing more effective and personalised therapies for patients with SHH pathway-driven CNS tumours.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"83"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEK7 induces lactylation in Alzheimer's disease to promote pyroptosis in BV-2 cells.","authors":"Jing Cheng, Hui Zhao","doi":"10.1186/s13041-024-01156-9","DOIUrl":"10.1186/s13041-024-01156-9","url":null,"abstract":"<p><p>Alzheimer's disease (AD), an age-related neurodegenerative disorder, is characterized by irreversible brain tissue degeneration. The amyloid-β (Aβ) cascade hypothesis stands as the predominant paradigm explaining AD pathogenesis. This study aimed to elucidate the mechanisms underlying Aβ-induced pyroptosis in AD. AD models were established using amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and Aβ-treated BV-2 cells (5 µM, 24 h). NEK7 expression was evaluated in vitro and in vivo. Cell pyroptosis was assessed before and after NEK7 expression was inhibited in BV-2 cells. Adeno-associated virus (AAV) vectors carrying short hairpin RNA (shRNA) against NEK7 (AAV-sh-NEK7) were administered to mice to knockdown NEK7 in vivo. Spatial learning and memory abilities were evaluated using the Morris water maze test. The interaction between NEK7 and histone H4 lysine 12 lactylation (H4K12la) were then investigated. The results suggested that NEK7 expression was markedly elevated in both in vitro and in vivo AD models. Treatment with Aβ significantly reduced cell viability and enhanced pyroptosis in BV-2 cells; these effects were reversed by inhibiting NEK7. Furthermore, AD mice with NEK7 knockdown exhibited shorter escape latencies and increased time spent in the target quadrant, suggesting that NEK7 inhibition improved cognitive function and memory retention. Mechanistically, Aβ treatment induced histone lactylation in BV-2 cells, and suppression of lactylation attenuated NEK7 transcriptional activity and mRNA levels. In summary, elevated NEK7 expression promoted histone lactylation in BV-2 cells, thereby facilitating pyroptosis. Inhibition of NEK7 conferred protection against Aβ-induced cellular damage and enhanced cognitive performance and memory retention in AD model mice. Collectively, targeting NEK7 represents a potential therapeutic strategy for alleviating AD symptoms.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"81"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of exosome-mediated propagation of systemic inflammatory responses into the central nervous system.","authors":"Mahesh Chandra Kodali, Chinnu Salim, Saifudeen Ismael, Sarah Grace Lebovitz, Geng Lin, Francesca-Fang Liao","doi":"10.1186/s13041-024-01120-7","DOIUrl":"10.1186/s13041-024-01120-7","url":null,"abstract":"<p><p>The mechanisms through which systemic inflammation exerts its effect on the central nervous system (CNS) are still not completely understood. Exosomes are small (30 to 100 nm) membrane-bound extracellular vesicles released by most of the mammalian cells. Exosomes play a vital role in cell-to-cell communication. This includes regulation of inflammatory responses by shuttling mRNAs, miRNAs, and cytokines, both locally and systemically to the neighboring as well as distant cells to further modulate the transcriptional and/or translational states and affect the functional phenotype of those cells that have taken up these exosomes. The role of circulating blood exosomes leading to neuroinflammation during systemic inflammatory conditions was hereby characterized. Serum-derived exosomes from LPS-challenged mice (SDEL) were freshly isolated from the sera of the mice that were earlier treated with LPS and used to study the effects on neuroinflammation. Exosomes isolated from the sera of the mice injected with saline were used as a control. In-vitro studies showed that the SDEL upregulate pro-inflammatory cytokine gene expression in the murine cell lines of microglia (BV-2), astrocytes (C8-D1A), and cerebral microvascular endothelial cells (bEnd.3). To further study their effects in-vivo, SDEL were intravenously injected into normal adult mice. Elevated mRNA expression of pro-inflammatory cytokines was observed in the brains of SDEL recipient mice. Proteomic analysis of the SDEL confirmed the increased expression of inflammatory cytokines in them. Together, these results demonstrate and strengthen the novel role of peripheral circulating exosomes in causing neuroinflammation during systemic inflammatory conditions.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"80"},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}