Frontiers in Cellular Neuroscience最新文献

{"title":"Editorial: Neuromodulation technology: advances in optics and acoustics.","authors":"Meijun Ye, Chen Yang, Ji-Xin Cheng, Hyeon Jeong Lee, Ying Jiang, Linli Shi","doi":"10.3389/fncel.2024.1494457","DOIUrl":"https://doi.org/10.3389/fncel.2024.1494457","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1494457"},"PeriodicalIF":4.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461923","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 novel <i>KCNC3</i> gene variant in the voltage-dependent Kv3.3 channel in an atypical form of SCA13 with dominant central vertigo.","authors":"Felix P Bernhard, Sven Schütte, Moritz Heidenblut, Moritz Oehme, Susanne Rinné, Niels Decher","doi":"10.3389/fncel.2024.1441257","DOIUrl":"https://doi.org/10.3389/fncel.2024.1441257","url":null,"abstract":"<p><p>Potassium channel mutations play an important role in neurological diseases, such as spinocerebellar ataxia (SCA). SCA is a heterogeneous autosomal-dominant neurodegenerative disorder with multiple sub-entities, such as SCA13, which is characterized by mutations in the voltage-gated potassium channel Kv3.3 (<i>KCNC3</i>). In this study, we present a rare and atypical case of SCA13 with a predominant episodic central rotational vertigo, while the patient suffered only from mild progressive cerebellar symptoms, such as dysarthria, ataxia of gait and stand, and recently a cognitive impairment. In this patient, we identified a heterozygous variant in <i>KCNC3</i> (c.2023G > A, p.Glu675Lys) by next-generation sequencing. This Kv3.3^E675K variant was studied using voltage-clamp recordings in <i>Xenopus</i> oocytes. While typical SCA13 variants are dominant-negative, show shifts in the voltage-dependence of activation or an altered TBK1 regulation, the Kv3.3^E675K variant caused only a reduction in current amplitude and a more pronounced cumulative inactivation. Thus, the differences to phenotypes observed in patients with classical SCA13 mutations may be related to the mechanism of the observed Kv3.3 loss-of-function. Treatment of our patient with riluzole, a drug that is known to also activate potassium channels, turned out to be partly beneficial. Strikingly, we found that the Kv3.3 and Kv3.3^E675K inactivation and the frequency-dependent cumulative inactivation was antagonized by increased extracellular potassium levels. Thus, and most importantly, carefully elevated plasma potassium levels in the physiological range, or novel drugs attenuating Kv3.3 inactivation might provide novel therapeutic approaches to rescue potassium currents of SCA13 variants <i>per se</i>. In addition, our findings broaden the phenotypic spectrum of Kv3.3 variants, expanding it to atypical phenotypes of Kv3.3-associated neurological disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1441257"},"PeriodicalIF":4.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461919","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":"Loss of C1q alters the auditory brainstem response.","authors":"Sima M Chokr, Ashley Bui-Tran, Karina S Cramer","doi":"10.3389/fncel.2024.1464670","DOIUrl":"https://doi.org/10.3389/fncel.2024.1464670","url":null,"abstract":"<p><p>Neural circuits in the auditory brainstem compute interaural time and intensity differences used to determine the locations of sound sources. These circuits display features that are specialized for these functions. The projection from the ventral cochlear nucleus (VCN) to the medial nucleus of the trapezoid (MNTB) body travels along highly myelinated fibers and terminates in the calyx of Held. This monoinnervating synapse emerges during development as multiple inputs are eliminated. We previously demonstrated that elimination of microglia with a colony stimulating factor-1 inhibitor results in impaired synaptic pruning so that multiple calyceal terminals reside on principal cells of MNTB. This inhibitor also resulted in impaired auditory brainstem responses (ABRs), with elevated thresholds and increased peak latencies. Loss of the microglial fractalkine receptor, CX3CR1, decreased peak latencies in the ABR. The mechanisms underlying these effects are not known. One prominent microglial signaling pathway involved in synaptic pruning and plasticity during development and aging is the C1q-initiated compliment cascade. Here we investigated the classical complement pathway initiator, C1q, in auditory brainstem maturation. We found that C1q expression is detected in the MNTB by the first postnatal week. C1q levels increased with age and were detected within microglia and surrounding the soma of MNTB principal neurons. Loss of C1q did not affect microglia-dependent calyceal pruning. Excitatory and inhibitory synaptic markers in the MNTB and LSO were not altered with C1q deletion. ABRs showed that C1q KO mice had normal hearing thresholds but shortened peak latencies. Altogether this study uncovers the developmental time frame of C1q expression in the sound localization pathway and shows a subtle functional consequence of C1q knockdown.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1464670"},"PeriodicalIF":4.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461924","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":"Noise-induced cochlear synaptopathy in C57BL/6 N mice as a function of trauma strength: ribbons are more vulnerable than postsynapses.","authors":"Kerstin Blum, Pauline Schepsky, Philip Derleder, Philipp Schätzle, Fahmi Nasri, Philipp Fischer, Jutta Engel, Simone Kurt","doi":"10.3389/fncel.2024.1465216","DOIUrl":"https://doi.org/10.3389/fncel.2024.1465216","url":null,"abstract":"<p><p>Noise-induced cochlear synaptopathy is characterized by irreversible loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) despite normal hearing thresholds. We analyzed hearing performance and cochlear structure in C57BL/6 N mice exposed to 100, 106, or 112 dB SPL broadband noise (8-16 kHz) for 2 h. Auditory brainstem responses (ABRs) were assessed before, directly after, and up to 28 days post-trauma. Finally, the number, size, and pairing of IHC presynaptic (CtBP2-positive) ribbons and postsynaptic AMPA receptor scaffold (Homer1-positive) clusters were analyzed along the cochlea. Four weeks after the 100 dB SPL trauma, a permanent threshold shift (PTS) was observed at 45 kHz, which after the higher traumata extended toward middle to low frequencies. Loss in ABR wave I amplitudes scaled with trauma strength indicating loss of functional IHC synaptic connections. Latencies of wave I mostly increased with trauma strength. No trauma-related OHC loss was found. The number of synaptic pairs was reduced in the midbasal and basal cochlear region in all trauma conditions, with ribbon loss amounting up to 46% of control. Ribbons surviving the trauma were paired, whereas 4-6 unpaired postsynapses/IHC were found in the medial, midbasal, and basal regions irrespective of trauma strength, contrasting findings in CBA/CaJ mice. Our data confirm the susceptibility of ribbon synapses and ABR wave I amplitudes to a noise trauma of 100 dB SPL or larger. Notably, peripheral dendrites bearing IHC postsynapses were less vulnerable than presynaptic ribbons in C57BL/6 N mice.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1465216"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461925","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":"Ammonium chloride reduces excitatory synaptic transmission onto CA1 pyramidal neurons of mouse organotypic slice cultures.","authors":"Dimitrios Kleidonas, Louis Hilfiger, Maximilian Lenz, Dieter Häussinger, Andreas Vlachos","doi":"10.3389/fncel.2024.1410275","DOIUrl":"https://doi.org/10.3389/fncel.2024.1410275","url":null,"abstract":"<p><p>Acute liver dysfunction commonly leads to rapid increases in ammonia concentrations in both the serum and the cerebrospinal fluid. These elevations primarily affect brain astrocytes, causing modifications in their structure and function. However, its impact on neurons is not yet fully understood. In this study, we investigated the impact of elevated ammonium chloride levels (NH₄Cl, 5 mM) on synaptic transmission onto CA1 pyramidal neurons in mouse organotypic entorhino-hippocampal tissue cultures. We found that acute exposure to NH₄Cl reversibly reduced excitatory synaptic transmission and affected CA3-CA1 synapses. Notably, NH₄Cl modified astrocytic, but not CA1 pyramidal neuron, passive intrinsic properties. To further explore the role of astrocytes in NH₄Cl-induced attenuation of synaptic transmission, we used methionine sulfoximine to target glutamine synthetase, a key astrocytic enzyme for ammonia clearance in the central nervous system. Inhibition of glutamine synthetase effectively prevented the downregulation of excitatory synaptic activity, underscoring the significant role of astrocytes in adjusting excitatory synapses during acute ammonia elevation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1410275"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461920","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":"Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders.","authors":"Isabel E Faulkner, Rachael Z Pajak, Michael K Harte, Jocelyn D Glazier, Reinmar Hager","doi":"10.3389/fncel.2024.1449151","DOIUrl":"https://doi.org/10.3389/fncel.2024.1449151","url":null,"abstract":"<p><p>Voltage-gated potassium channels are a widely distributed subgroup of potassium channels responsible for the efflux of potassium in the repolarisation of the cell membrane, and hence contribute to the latency and propagation of action potentials. As they are causal to synaptic transmission, alterations to the structure of these channels can lead to a variety of neurological and psychiatric diseases. The Kv3 subfamily of voltage-gated potassium channels are found on many neurons in the brain, including inhibitory interneurons where they contribute to fast-frequency firing. Changes to the firing ability of these interneurons can lead to an imbalance of inhibitory and excitatory neurotransmission. To date, we have little understanding of the mechanism by which excitatory and inhibitory inputs become imbalanced. This imbalance is associated with cognitive deficits seen across neurological and neuropsychiatric disorders, which are currently difficult to treat. In this review, we collate evidence supporting the hypothesis that voltage-gated potassium channels, specifically the Kv3 subfamily, are central to many neurological and psychiatric disorders, and may thus be considered as an effective drug target. The collective evidence provided by the studies reviewed here demonstrates that Kv3 channels may be amenable to novel treatments that modulate the activity of these channels, with the prospect of improved patient outcome.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1449151"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461927","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":"Anatomical and molecular development of the human primary visual cortex.","authors":"Kathryn M Murphy, Leanne Monteiro","doi":"10.3389/fncel.2024.1427515","DOIUrl":"https://doi.org/10.3389/fncel.2024.1427515","url":null,"abstract":"<p><p>The human primary visual cortex (V1) development is pivotal to understanding cortical maturation and neuroplasticity. Theories on V1 development range from early maturation models, which emphasize the early peak of synapses in infancy, to those suggesting an extended developmental timeline where key plasticity mechanisms continue to mature well into adulthood. Classic histological approaches have supported early development, while recent molecular studies highlight prolonged or multiple windows of plasticity, indicating that V1 remains susceptible to experience-dependent modifications beyond childhood. This review consolidates findings from both anatomical and molecular studies, tracing the development of V1 from prenatal stages through aging. The evidence reveals that human V1 develops across multiple timescales, with some aspects maturing early and others gradually changing across the lifespan. Reflecting on Cajal's early work, this review underscores the importance of methodological advancements in revealing the intricate details of V1's development.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1427515"},"PeriodicalIF":4.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461921","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":"Anti-neuroinflammatory effects of conjugated linoleic acid isomers, c9,t11 and t10,c12, on activated BV-2 microglial cells.","authors":"Clara Porcedda, Claudia Manca, Gianfranca Carta, Franca Piras, Sebastiano Banni, Valeria Sogos, Elisabetta Murru","doi":"10.3389/fncel.2024.1442786","DOIUrl":"https://doi.org/10.3389/fncel.2024.1442786","url":null,"abstract":"<p><p>Conjugated linoleic acid (CLA) isomers exhibit anti-inflammatory properties within the central nervous system (CNS). This study investigated the effects of CLA isomers c9,t11 and t10,c12 on fatty acid (FA) and <i>N-</i>acylethanolamine (NAE) profiles and their association with pro-inflammatory molecule expression in BV-2 microglia cell line, the CNS's resident immune cells responsible for maintaining neuronal activity and immune homeostasis. BV-2 cells were treated with 25 μM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 h, followed by lipopolysaccharide (LPS) stimulation. After treatment, the cell's FA and NAE profiles and pro-inflammatory molecule expression were analyzed. Our results demonstrated that CLA isomers mitigate LPS-induced morphological changes in BV-2 cells and reduce gene expression and protein levels of inflammatory markers. This effect was linked to an upregulation of acyl-CoA oxidase 1, a key enzyme in the anti-inflammatory peroxisomal beta-oxidation pathway that efficiently metabolizes CLA isomers. Notably, t10,c12-CLA significantly suppressed stearoyl-CoA desaturase 1, impacting monounsaturated fatty acid synthesis. The NAEs profile was remarkably altered by CLA isomers, with a significant release of the anti-neuroinflammatory mediator docosahexaenoic acid (DHA)-derived <i>N-</i>acylethanolamine (DHAEA). In conclusion, our findings suggest that the anti-neuroinflammatory effects of CLA isomers are due to their unique influences on FA metabolism and the modulation of bioactive FA-derived NAEs, highlighting a potential strategy for nutritional intervention in conditions characterized by neuroinflammation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1442786"},"PeriodicalIF":4.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461922","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":"Corrigendum: Contribution of thyrotropin-releasing hormone to cerebellar long-term depression and motor learning.","authors":"Masashi Watanave, Yasunori Matsuzaki, Yasuyo Nakajima, Atsushi Ozawa, Masanobu Yamada, Hirokazu Hirai","doi":"10.3389/fncel.2024.1495155","DOIUrl":"https://doi.org/10.3389/fncel.2024.1495155","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncel.2018.00490.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1495155"},"PeriodicalIF":4.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399878","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":"Editorial: Gateways to the brain: vascular-glial-immune network in health and disease.","authors":"Diana Matias, Patrícia P Garcez, Helena Florindo, Luis Graça, Luiz Gustavo Dubois","doi":"10.3389/fncel.2024.1461604","DOIUrl":"https://doi.org/10.3389/fncel.2024.1461604","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1461604"},"PeriodicalIF":4.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399879","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}