{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T04:15:41Z","timestamp":1781928941263,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Apoptosis has been recognized as a critical pathophysiological process during cerebral ischemia. The neuroprotective effect of CART on ischemic brain injury is determined. However, there is little research on the protective effect of CART on neural stem cells (NSCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary cultured rat NSCs were utilized as the research subject. <jats:italic>In vitro<\/jats:italic> oxygen glucose deprivation (OGD) treatment was employed, and NSCs were extracted from SD pregnant rats following previous experimental protocols and identified through cell immunofluorescence staining. The appropriate concentration of CART affecting OGD NSCs was initially screened using Cell Counting Kit-8 (CCK-8) and Lactate Dehydrogenase (LDH) assays. EdU staining and Western blotting (WB) techniques were employed to assess the impact of the suitable CART concentration on the proliferation and apoptosis of OGD NSCs. Finally, Western blot analysis was conducted to investigate the cAMP-response element binding protein (CREB) pathway and expression levels of related proteins after KG-501 treatment in order to elucidate the mechanism underlying apoptosis and proliferation regulation in OGD NSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CCK-8 and LDH assays indicated that a concentration of 0.8\u2009nM CART may be the optimal concentration for modulating the proliferation of OGD NSCs. Subsequently, cellular immunofluorescence and EdU detection experiments further confirmed the findings obtained from CCK-8 analysis. Western blot analysis of apoptosis-related protein expression also demonstrated that an appropriate concentration of CART could suppress the apoptosis of OGD NSCs. Finally, Western blotting was conducted to examine the CREB pathway and related protein expression after treatment with KG-501, revealing that an appropriate concentration of CART regulated both apoptosis and proliferation in OGD NSCs through CREB signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The concentration of CART at 0.8\u2009nM may be deemed appropriate for inhibiting apoptosis and promoting proliferation in OGD NSCs <jats:italic>in vitro<\/jats:italic>. The mechanism maybe through activating the CREB pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2024.1424719","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T04:31:52Z","timestamp":1724128312000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cocaine amphetamine-regulated transcription peptide inhibits apoptosis in oxygen\u2013glucose deprived neural stem cells"],"prefix":"10.3389","volume":"18","author":[{"given":"Lu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moxi","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dujuan","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.peptides.2018.10.008","article-title":"Cocaine-and amphetamine-regulated transcript (CART): A multifaceted neuropeptide","volume":"110","author":"Ahmadian-Moghadam","year":"2018","journal-title":"Peptides"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/s0140-6736(20)31179-x","article-title":"Stroke","volume":"396","author":"Campbell","year":"2020","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.1038\/s41467-018-04445-9","article-title":"CREB controls cortical circuit plasticity and functional recovery after stroke","volume":"9","author":"Caracciolo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1007\/s00429-017-1544-6","article-title":"CART neurons in the lateral hypothalamus communicate with the nucleus accumbens shell via glutamatergic neurons in paraventricular thalamic nucleus to modulate reward behavior","volume":"223","author":"Choudhary","year":"2018","journal-title":"Brain Struct. Funct."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"657846","DOI":"10.3389\/fcell.2021.657846","article-title":"Post-stroke Neurogenesis: Friend or Foe?","volume":"9","author":"Cuartero","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1016\/j.peptides.2006.01.025","article-title":"The CART gene: structure and regulation","volume":"27","author":"Dominguez","year":"2006","journal-title":"Peptides"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1523\/jneurosci.15-03-02471.1995","article-title":"PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine","volume":"15","author":"Douglass","year":"1995","journal-title":"J. Neurosci."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/3473","article-title":"Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes","volume":"16","author":"Flax","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.cell.2016.10.021","article-title":"Adult neurogenesis in the Hippocampus: from stem cells to behavior","volume":"167","author":"Gon\u00e7alves","year":"2016","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3390\/ijms22147703","article-title":"Neural stem cells for early ischemic stroke","volume":"22","author":"Hamblin","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1056\/NEJMoa2213379","article-title":"Trial of endovascular therapy for acute ischemic stroke with large infarct","volume":"388","author":"Huo","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nm.2399","article-title":"The immunology of stroke: from mechanisms to translation","volume":"17","author":"Iadecola","year":"2011","journal-title":"Nat. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1177\/0963689718819994","article-title":"MRI tracking of iPS cells-induced neural stem cells in traumatic brain injury rats","volume":"28","author":"Jiang","year":"2019","journal-title":"Cell Transplant."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1073\/pnas.0806518106","article-title":"Synaptic activity-responsive element in the arc\/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons","volume":"106","author":"Kawashima","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1007\/bf00688633","article-title":"The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion","volume":"68","author":"Kuroiwa","year":"1985","journal-title":"Acta Neuropathol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"3298","DOI":"10.3892\/mmr.2018.9296","article-title":"Cocaine-and amphetamine-regulated transcript (CART) is associated with dopamine and is protective against ischemic stroke","volume":"18","author":"Lin","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/jcbfm.2012.172","article-title":"CART peptide induces neuroregeneration in stroke rats","volume":"33","author":"Luo","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e29343","DOI":"10.1371\/journal.pone.0029343","article-title":"CART peptide is a potential endogenous antioxidant and preferentially localized in mitochondria","volume":"7","author":"Mao","year":"2012","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/s1474-4422(09)70182-6","article-title":"Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study","volume":"8","author":"Mazighi","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s12975-010-0047-z","article-title":"Proteomic protease substrate profiling of tPA treatment in acute ischemic stroke patients: A step toward individualizing thrombolytic therapy at the bedside","volume":"1","author":"Ning","year":"2010","journal-title":"Transl. Stroke Res."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fneur.2020.00148","article-title":"Therapeutic plasticity of neural stem cells","volume":"11","author":"Ottoboni","year":"2020","journal-title":"Front. Neurol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/s0140-6736(18)31269-8","article-title":"Prevention of stroke: a global perspective","volume":"392","author":"Pandian","year":"2018","journal-title":"Lancet"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.stem.2015.10.006","article-title":"Imported stem cells strike against stroke","volume":"17","author":"P\u00e9ron","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1056\/NEJMcp1917030","article-title":"Acute Ischemic Stroke","volume":"383","author":"Powers","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1161\/strokeaha.122.040073","article-title":"Projected global trends in ischemic stroke incidence, deaths and disability-adjusted life years from 2020 to 2030","volume":"54","author":"Pu","year":"2023","journal-title":"Stroke"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12975-020-00841-w","article-title":"Neurogenesis after stroke: A therapeutic perspective","volume":"12","author":"Rahman","year":"2021","journal-title":"Transl. Stroke Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3298","DOI":"10.1093\/brain\/aws259","article-title":"Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke mice","volume":"135","author":"Sakata","year":"2012","journal-title":"Brain"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1369-1600.2012.00475.x","article-title":"Reduced ethanol consumption and preference in cocaine-and amphetamine-regulated transcript (CART) knockout mice","volume":"19","author":"Salinas","year":"2014","journal-title":"Addict. Biol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1097\/WNR.0b013e328363f7a1","article-title":"A cocaine-regulated and amphetamine-regulated transcript inhibits oxidative stress in neurons deprived of oxygen and glucose","volume":"24","author":"Sha","year":"2013","journal-title":"Neuroreport"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.brainres.2014.07.043","article-title":"Cocaine-and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons","volume":"1582","author":"Sha","year":"2014","journal-title":"Brain Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.bbr.2018.03.035","article-title":"Cocaine-and amphetamine-regulated transcript peptide (CART) induced reward behavior is mediated via G(i\/o) dependent phosphorylation of PKA\/ERK\/CREB pathway","volume":"348","author":"Somalwar","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1089\/cell.2012.0081","article-title":"Tracking induced pluripotent stem cells-derived neural stem cells in the central nervous system of rats and monkeys","volume":"15","author":"Tang","year":"2013","journal-title":"Cell. Reprogram."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"14489","DOI":"10.1073\/pnas.0602932103","article-title":"Role of cocaine-and amphetamine-regulated transcript in estradiol-mediated neuroprotection","volume":"103","author":"Xu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"7029","DOI":"10.1073\/pnas.96.12.7029","article-title":"\"global\" cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain","volume":"96","author":"Yandava","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1038\/nm.2022","article-title":"Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery","volume":"15","author":"Yemisci","year":"2009","journal-title":"Nat. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1056\/NEJMoa2118191","article-title":"Endovascular therapy for acute stroke with a large ischemic region","volume":"386","author":"Yoshimura","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/s0140-6736(18)31874-9","article-title":"Current practice and future directions in the diagnosis and acute treatment of ischaemic stroke","volume":"392","author":"Zerna","year":"2018","journal-title":"Lancet"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"102023","DOI":"10.1016\/j.npep.2020.102023","article-title":"Cocaine-and amphetamine-regulated transcript protects synaptic structures in neurons after ischemic cerebral injury","volume":"81","author":"Zhang","year":"2020","journal-title":"Neuropeptides"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1111\/j.1440-1681.2011.05642.x","article-title":"Roles of cocaine-and amphetamine-regulated transcript in the central nervous system","volume":"39","author":"Zhang","year":"2012","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"817","DOI":"10.4252\/wjsc.v11.i10.817","article-title":"Neural stem cell transplantation therapy for brain ischemic stroke: review and perspectives","volume":"11","author":"Zhang","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s12975-022-00984-y","article-title":"Neural stem cells therapy for ischemic stroke: Progress and challenges","volume":"13","author":"Zhao","year":"2022","journal-title":"Transl. Stroke Res."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"97","DOI":"10.2174\/1389450053345055","article-title":"Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation","volume":"6","author":"Zhu","year":"2005","journal-title":"Curr. Drug Targets"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.1056\/NEJMc055304","article-title":"Tracking neural stem cells in patients with brain trauma","volume":"355","author":"Zhu","year":"2006","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2024.1424719\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T04:31:53Z","timestamp":1724128313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2024.1424719\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":43,"alternative-id":["10.3389\/fnins.2024.1424719"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2024.1424719","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]},"article-number":"1424719"}}