{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:02:05Z","timestamp":1791007325944,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T00:00:00Z","timestamp":1218672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p>\n                    Hyperhomocysteinemia (HHcy)\u2014abnormally elevated plasma levels of homocysteine (Hcy)\u2014has been associated with the development of neurodegenerative dementia and mild cognitive impairment. This association suggests that HHcy might facilitate memory loss in the elderly. As memory loss can occur through a deteriorated neurogenic capacity, we have studied the effects of Hcy on neural progenitor cells (NPCs) both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We show that Hcy exerts an antiproliferative effect on basic fibroblast growth factor (bFGF) \u2010stimulated NPCs isolated from the postnatal subventricular zone (SVZ), accompanied by inactivation of the extracellular signal\u2010regulated kinase (Erk1\/2) and inhibition of Erk1\/ 2\u2010dependent expression of cyclin E. Using a mice model we show that, under normal folate conditions, HHcy exerts an inhibitory effect on adult brain neurogenesis. This inhibition occurs in the caudal areas of the dentate gyrus (DG) of the hippocampus, a neurogenic area mainly involved in learning and memory performance, and in the SVZ, recently implicated in olfactory learning performance. In both areas reduced number of proliferative neuroblasts were found. Since neuroblasts are primarily bFGF\u2010responsive progenitors already committed to a neuronal phenotype, our results strongly suggest that excess Hcyinhibits neurogenesis in the DG and SVZ byinhibiting the bFGF\u2010dependent activation of Erk1\/2 in these cells.\u2014 Rabaneda, L. G., Carrasco, M., Lopez\u2010Toledano, M. A., Murillo\u2010Carretero, M., Ruiz, F. A., Estrada, C., Castro, C. Homocysteine inhibits proliferation of neuronal precursors in the mouse adult brain by impairing the basic fibroblast growth factor signaling cascade and reducing extracellular regulated kinase 1\/2\u2010dependent cyclin E expression.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 3823\u20133835 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-109306","type":"journal-article","created":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T21:06:56Z","timestamp":1218748016000},"page":"3823-3835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Homocysteine inhibits proliferation of neuronal precursors in the mouse adult brain by impairing the basic fibroblast growth factor signaling cascade and reducing extracellular regulated kinase 1\/2\u2010dependent cyclin E expression"],"prefix":"10.1096","volume":"22","author":[{"given":"Luis G.","family":"Rabaneda","sequence":"first","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"L\u00f3pez\u2010Toledano","sequence":"additional","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maribel","family":"Murillo\u2010Carretero","sequence":"additional","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix A.","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"},{"name":"Hospital Universitario Puerta del Mar C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Estrada","sequence":"additional","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Castro","sequence":"additional","affiliation":[{"name":"Area de Fisiologia, Facultad de Medicina Universidad de C\u00e1diz C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,8,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011613"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.08.012"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.49.1.31"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.2.511"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60109-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01752.2002"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06920.2000"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nn1707","article-title":"Potential role for adult neurogenesis in the encoding of time in new memories","volume":"9","author":"Amone J. 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