Developmental Neuroscience最新文献

{"title":"Neurochemical Profile of BRAFV600E/AktT308D/S473D Mouse Gangliogliomas Reveals Impaired GABAergic System Inhibition.","authors":"Maria Kyriazi,&nbsp;Philipp Müller,&nbsp;Julika Pitsch,&nbsp;Karen M J van Loo,&nbsp;Anne Quatraccioni,&nbsp;Thoralf Opitz,&nbsp;Susanne Schoch,&nbsp;Albert J Becker,&nbsp;Silvia Cases-Cunillera","doi":"10.1159/000528587","DOIUrl":"https://doi.org/10.1159/000528587","url":null,"abstract":"<p><p>Gangliogliomas (GGs), composed of dysmorphic neurons and neoplastic astroglia, represent the most frequent tumor entity associated with chronic recurrent epileptic seizures. So far, a systematic analysis of potential differences in neurochemical profiles of dysmorphic tumoral neurons as well as neurons of the peritumoral microenvironment (PTME) was hampered by the inability to unequivocally differentiate between the distinct neuronal components in human GG biopsies. Here, we have applied a novel GG mouse model that allows to clearly resolve the neurochemical profiles of GG-intrinsic versus PTME neurons. For this purpose, glioneuronal tumors in mice were induced by intraventricular in utero electroporation (IUE) of piggyBac-based plasmids for BRAFV600E and activated Akt (AktT308D/S473D, further referred to as AktDD) and analyzed neurochemically by immunocytochemistry against specific marker proteins. IUE of BRAFV600E/AktDD in mice resulted in tumors with the morphological features of human GGs. Our immunocytochemical analysis revealed a strong reduction of GABAARα1 immunoreactivity in the tumor compared to the PTME. In contrast, the extent of NMDAR1 immunoreactivity in the tumor appeared comparable to the PTME. Interestingly, tumor cells maintained the potential to express both receptors. Fittingly, the abundance of the presynaptic vesicular neurotransmitter transporters VGLUT1 and VGAT was also decreased in the tumor. Additionally, the fraction of parvalbumin and somatostatin nonneoplastic interneurons was reduced. In conclusion, changes in the levels of key proteins in neurotransmitter signaling suggest a loss of synapses and may thereby lead to neuronal network alterations in mouse GGs.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 2","pages":"53-65"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In utero Exposure to Valproic Acid throughout Pregnancy Causes Phenotypes of Autism in Offspring Mice.","authors":"Takayuki Mitsuhashi,&nbsp;Satoko Hattori,&nbsp;Kimino Fujimura,&nbsp;Shinsuke Shibata,&nbsp;Tsuyoshi Miyakawa,&nbsp;Takao Takahashi","doi":"10.1159/000530452","DOIUrl":"10.1159/000530452","url":null,"abstract":"<p><p>Valproic acid (VPA) is an antiepileptic drug that inhibits the epileptic activity of neurons mainly by inhibiting sodium channels and GABA transaminase. VPA is also known to inhibit histone deacetylases, which epigenetically modify the cell proliferation/differentiation characteristics of stem/progenitor cells within developing tissues. Recent clinical studies in humans have indicated that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in offspring; we have previously reported that low-dose VPA exposure in utero throughout pregnancy increases the production of projection neurons from neuronal stem/progenitor cells that are distributed in the superficial neocortical layers of the fetal brain. In the present study, we found that in utero VPA-exposed mice exhibited abnormal social interaction, changes in cognitive function, hypersensitivity to pain/heat, and impaired locomotor activity, all of which are characteristic symptoms of autism spectrum disorder in humans. Taken together, our findings indicate that VPA exposure in utero throughout pregnancy alters higher brain function and predisposes individuals to phenotypes that resemble autism and intellectual disability. Furthermore, these symptoms are likely to be due to neocortical dysgenesis that was caused by an increased number of projection neurons in specific layers of the neocortex.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"223-233"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9290265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression Analyses of Rich2/Arhgap44, a Rho Family GTPase-Activating Protein, during Mouse Brain Development.","authors":"Naoki Goto,&nbsp;Masashi Nishikawa,&nbsp;Hidenori Ito,&nbsp;Mariko Noda,&nbsp;Nanako Hamada,&nbsp;Hidenori Tabata,&nbsp;Makoto Kinoshita,&nbsp;Koh-Ichi Nagata","doi":"10.1159/000529051","DOIUrl":"https://doi.org/10.1159/000529051","url":null,"abstract":"<p><p>Rho family small GTPases, such as Rho, Rac, and Cdc42, play essential roles during brain development, by regulating cellular signaling and actin cytoskeletal reorganization. Rich2/Arhgap44, a Rac- and Cdc42-specific GTPase-activating protein, has been reported to be a key regulator for dendritic spine morphology and synaptic function. Given the essential roles of Rac and Cdc42 in brain development, Rich2 is supposed to take part in brain development. However, not only the molecular mechanism involved but also the expression profile of Rich2 during neurodevelopment has not yet been elucidated. In this study, we carried out expression analyses of Rich2 by focusing on mouse brain development. In immunoblotting, Rich2 exhibited a tissue-dependent expression profile in the young adult mouse, and the expression was increased during brain development. In immunohistochemical analyses, Rich2 was observed in the cytoplasm of cortical neurons at postnatal day (P) 0 and then came to be enriched in the nucleus with moderate distribution in neuropils at P7. Later at P30, a complex immunostaining pattern of Rich2 was observed; Rich2 was distributed in the nucleus, cytoplasm, and neuropils in many cortical neurons, whereas other neurons frequently displayed little expression. In the hippocampus at P7, Rich2 was distributed mainly in the cytoplasm of excitatory neurons in the cornu ammonis regions, while it was moderately detected in the nucleus in the dentate granule cells. Notably, Rich2 was distributed in excitatory synapses of the cornu ammonis 1 region at P30. Biochemical fractionation analyses also detected Rich2 in the postsynaptic density. Taken together, Rich2 is found to be expressed in the central nervous system in a developmental stage-dependent manner and may be involved in synapse formation/maintenance in cortical neurons.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 1","pages":"19-26"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of C4 Gene Copy Number in Pediatric Acute Neuropsychiatric Syndrome.","authors":"Agnieszka Kalinowski, Lu Tian, Reenal Pattni, Hanna Ollila, Maroof Khan, Cindy Manko, Melissa Silverman, Meiqian Ma, Laurie Columbo, Bahare Farhadian, Susan Swedo, Tanya Murphy, Mats Johnson, Elisabeth Fernell, Christopher Gillberg, Margo Thienemann, Elizabeth D Mellins, Douglas F Levinson, Alexander E Urban, Jennifer Frankovich","doi":"10.1159/000531707","DOIUrl":"10.1159/000531707","url":null,"abstract":"<p><p>Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of comorbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) were used to assess whether the time to juvenile idiopathic arthritis (JIA) or autoimmune disease (AI) onset was a function of total C4A or C4B CN. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes, and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (hazard ratio = 2.7, p value = 0.004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis, and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"315-324"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10070131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual Dimorphism in the Closure of the Hippocampal Postnatal Critical Period of Synaptic Plasticity after Intrauterine Growth Restriction: Link to Oligodendrocyte and Glial Dysregulation.","authors":"Michael Nugent,&nbsp;Mark St Pierre,&nbsp;Ashley Brown,&nbsp;Salma Nassar,&nbsp;Pritika Parmar,&nbsp;Yuma Kitase,&nbsp;Sarah Ann Duck,&nbsp;Charles Pinto,&nbsp;Lauren Jantzie,&nbsp;Camille Fung,&nbsp;Raul Chavez-Valdez","doi":"10.1159/000530451","DOIUrl":"10.1159/000530451","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Intrauterine growth restriction (IUGR) resulting from hypertensive disease of pregnancy (HDP) leads to sexually dimorphic hippocampal-dependent cognitive and memory impairment in humans. In our translationally relevant mouse model of IUGR incited by HDP, we have previously shown that the synaptic development in the dorsal hippocampus including GABAergic development, NPTX2+ excitatory synaptic formation, axonal myelination, and perineural net (PNN) formation were perturbed by IUGR at adolescent equivalence in humans (P40). The persistence of these disturbances through early adulthood and the potential upstream mechanisms are currently unknown. Thus, we hypothesized that NPTX2+ expression, PNN formation, axonal myelination, all events closing synaptic development in the hippocampus, will be persistently perturbed, particularly affecting IUGR female mice through P60 given the fact that they had worse short-term recognition memory in this model. We additionally hypothesized that such sexual dimorphism is linked to persistent glial dysregulation. We induced IUGR by a micro-osmotic pump infusion of a potent vasoconstrictor U-46619, a thromboxane A2-analog, in the last week of the C57BL/6 mouse gestation to precipitate HDP. Sham-operated mice were used as controls. At P60, we assessed hippocampal and hemispheric volumes, NPTX2 expression, PNN formation, as well as myelin basic protein (MBP), Olig2, APC/CC1, and M-NF expression. We also evaluated P60 astrocytic (GFAP) reactivity and microglial (Iba1 and TMEM119) activation using immunofluorescent-immunohistochemistry and Imaris morphological analysis plus cytokine profiling using Meso Scale Discovery platform. IUGR offspring continued to have smaller hippocampal volumes at P60 not related to changes in hemisphere volume. NPTX2+ puncta counts and volumes were decreased in IUGR hippocampal CA subregions of female mice compared to sex-matched shams. Intriguingly, NPTX2+ counts and volumes were concurrently increased in the dentate gyrus (DG) subregion. PNN volumes were smaller in CA1 and CA3 of IUGR female mice along with PNN intensity in CA3 but they had larger volumes in the CA3 of IUGR male mice. The myelinated axon (MBP+) areas, volumes, and lengths were all decreased in the CA1 of IUGR female mice compared to sex-matched shams, which correlated with a decrease in Olig2 nuclear expression. No decrease in the number of APC/CC1+ mature oligodendrocytes was identified. We noted an increase in M-NF expression in the mossy fibers connecting DG to CA3 only in IUGR female mice. Reactive astrocytes denoted by GFAP areas, volumes, lengths, and numbers of branching were increased in IUGR female CA1 but not in IUGR male CA3 compared to sex-matched shams. Lastly, activated microglia were only detected in IUGR female CA1 and CA3 subregions. We detected no difference in the cytokine profile between sham and IUGR adult mice of either sex. Collectively, our data support a sexually dimorphic impaired closure of po","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"234-254"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9306757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippo Pathway in Schwann Cells and Regeneration of Peripheral Nervous System.","authors":"Jingyuan Wang,&nbsp;Haofeng Chen,&nbsp;Wulei Hou,&nbsp;Qingjian Han,&nbsp;Zuoyun Wang","doi":"10.1159/000530621","DOIUrl":"10.1159/000530621","url":null,"abstract":"<p><p>Hippo pathway is an evolutionarily conserved signaling pathway comprising a series of MST/LATS kinase complexes. Its key transcriptional coactivators YAP and TAZ regulate transcription factors such as TEAD family to direct gene expression. The regulation of Hippo pathway, especially the nuclear level change of YAP and TAZ, significantly influences the cell fate switching from proliferation to differentiation, regeneration, and postinjury repair. This review outlines the main findings of Hippo pathway in peripheral nerve development, regeneration, and tumorigenesis, especially the studies in Schwann cells. We also summarize other roles of Hippo pathway in damage repair of the peripheral nerve system and discuss the potential future research which probably contributes to novel therapeutic strategies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"276-289"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9426315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone as a Neuroprotective Agent in Neonatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review.","authors":"Ming-Te Lee,&nbsp;Rosin McNicholas,&nbsp;Lawrence Miall,&nbsp;Nigel Simpson,&nbsp;Kevin C W Goss,&nbsp;Nicola J Robertson,&nbsp;Paul Chumas","doi":"10.1159/000521540","DOIUrl":"https://doi.org/10.1159/000521540","url":null,"abstract":"<p><p>Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of progesterone (PROG) include anti-apoptotic, anti-inflammatory, and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema, and excitotoxicity. In pre-clinical studies of neonatal HIE, PROG has neuroprotective properties but has not been the subject of systematic review. Here, our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria. Population: human neonates with HIE/animal models of HIE; intervention: PROG +/- other agents; comparison: V.S. control; outcome: pathological, neurobehavioural, and mechanistic outcome measures. Medline, EMBASE, and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and keywords. Study inclusion, data extraction, and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG reduced neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) insult in 8 and 3 studies, respectively. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies, and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing, and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without TH.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 2","pages":"76-93"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvedilol Reduces the Neuronal Apoptosis after Ischemic Stroke by Modulating Activator of Transcription 3 Expression in vitro.","authors":"Zhao Zheng,&nbsp;Fei Hou,&nbsp;Guodong He,&nbsp;Fengfeng Jiang,&nbsp;Xiang Bao,&nbsp;Minfeng Tong","doi":"10.1159/000527484","DOIUrl":"https://doi.org/10.1159/000527484","url":null,"abstract":"<p><p>Cerebral ischemia is divided into local cerebral ischemia and diffuse cerebral ischemia. The etiology of localized cerebral ischemia includes middle cerebral artery embolism; stenosis, occlusion, or thrombosis of extracranial internal carotid artery or vertebral artery; and cerebral artery spasm. The causes of diffuse cerebral ischemia include cardiac arrest, hypotension, anemia, and hypoglycemia. However, the underlying mechanism is still unclear. In this study, we demonstrated that activator of transcription 3 (ATF3) is a hubgene in IS by bioinformatics analysis. The expression of ATF3 was increased in PC12 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. ATF3 deficiency inhibited cell viability and induced cell apoptosis, whereas ATF3 overexpression showed the opposite role in cell viability and cell apoptosis. Moreover, Carvedilol as a compound targeting ATF3 also facilitated cell viability and reduced cell apoptosis. ATF3 deficiency retarded the increase in cell viability and inhibition of cell apoptosis in OGD/R-PC12 cells with Carvedilol treatment. Additionally, the decreased Bax and cleaved caspase-3 were released in OGD/R-PC12 cells with Carvedilol and siATF3 treatment, while Bcl-2 expression was inhibited in OGD/R-PC12 cells with Carvedilol and siATF3 treatment. In conclusion, Carvedilol may be a key compound targeting ATF3 in OGD/R-PC12 cells. Graphical Abstract: Carvedilol positively regulated cell viability and negatively regulated cell apoptosis in OGD/R-PC12 cells by inhibition of ATF3.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 2","pages":"94-104"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9728282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Macrocephaly, as an Isolated Trait, on EEG Signal as Measured by Spectral Power and Multiscale Entropy during the First Year of Life.","authors":"Gabriela López-Arango,&nbsp;Florence Deguire,&nbsp;Kristian Agbogba,&nbsp;Élisabeth Audet-Duchesne,&nbsp;Marc-Antoine Boucher,&nbsp;Inga S Knoth,&nbsp;Ramy El-Jalbout,&nbsp;Amélie Damphousse,&nbsp;Samuel Kadoury,&nbsp;Sarah Lippé","doi":"10.1159/000529722","DOIUrl":"https://doi.org/10.1159/000529722","url":null,"abstract":"<p><p>Macrocephaly has been associated with neurodevelopmental disorders; however, it has been mainly studied in the context of pathological or high-risk populations and little is known about its impact, as an isolated trait, on brain development in general population. Electroencephalographic (EEG) power spectral density (PSD) and signal complexity have shown to be sensitive to neurodevelopment and its alterations. We aimed to investigate the impact of macrocephaly, as an isolated trait, on EEG signal as measured by PSD and multiscale entropy during the first year of life. We recorded high-density EEG resting-state activity of 74 healthy full-term infants, 50 control (26 girls), and 24 macrocephalic (12 girls) aged between 3 and 11 months. We used linear regression models to assess group and age effects on EEG PSD and signal complexity. Sex and brain volume measures, obtained via a 3D transfontanellar ultrasound, were also included into the models to evaluate their contribution. Our results showed lower PSD of the low alpha (8-10 Hz) frequency band and lower complexity in the macrocephalic group compared to the control group. In addition, we found an increase in low alpha (8.5-10 Hz) PSD and in the complexity index with age. These findings suggest that macrocephaly as an isolated trait has a significant impact on brain activity during the first year of life.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 4","pages":"210-222"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cilia at the Crossroads of Tumor Treating Fields and Chemotherapy.","authors":"Loic P Deleyrolle, Matthew R Sarkisian","doi":"10.1159/000529193","DOIUrl":"10.1159/000529193","url":null,"abstract":"<p><p>Glioblastoma (GBM), the most common and lethal primary brain tumor in adults, requires multi-treatment intervention which unfortunately barely shifts the needle in overall survival. The treatment options after diagnosis and surgical resection (if possible) include irradiation, temozolomide (TMZ) chemotherapy, and now tumor treating fields (TTFields). TTFields are electric fields delivered locoregionally to the head/tumor via a wearable medical device (Optune®). Overall, the concomitant treatment of TTFields and TMZ target tumor cells but spare normal cell types in the brain. Here, we examine whether primary cilia, microtubule-based \"antennas\" found on both normal brain cells and GBM cells, play specific roles in sensitizing tumor cells to treatment. We discuss evidence supporting GBM cilia being exploited by tumor cells to promote their growth and treatment resistance. We review how primary cilia on normal brain and GBM cells are affected by GBM treatments as monotherapy or concomitant modalities. We also focus on latest findings indicating a differential regulation of GBM ciliogenesis by TTFields and TMZ. Future studies await arrival of intracranial TTFields models to determine if GBM cilia carry a prognostic capacity.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":"45 1","pages":"139-146"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44255276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}