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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-dependent cyclin E expression.
FASEB J. 2008 Nov; 22(11):3823-35.FJ

Abstract

Hyperhomocysteinemia (HHcy)-abnormally elevated plasma levels of homocysteine (Hcy)-has 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 in vitro and in vivo. We show that Hcy exerts an antiproliferative effect on basic fibroblast growth factor (bFGF) -stimulated NPCs isolated from the postnatal subventricular zone (SVZ), accompanied by inactivation of the extracellular signal-regulated kinase (Erk1/2) and inhibition of Erk1/2-dependent 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-responsive progenitors already committed to a neuronal phenotype, our results strongly suggest that excess Hcy inhibits neurogenesis in the DG and SVZ by inhibiting the bFGF-dependent activation of Erk1/2 in these cells.

Authors+Show Affiliations

Area de Fisiologia, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18703672

Citation

Rabaneda, Luis G., et al. "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-dependent Cyclin E Expression." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 22, no. 11, 2008, pp. 3823-35.
Rabaneda LG, Carrasco M, López-Toledano MA, et al. 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-dependent cyclin E expression. FASEB J. 2008;22(11):3823-35.
Rabaneda, L. G., Carrasco, M., López-Toledano, M. A., Murillo-Carretero, M., Ruiz, F. A., Estrada, C., & Castro, C. (2008). 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-dependent cyclin E expression. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 22(11), 3823-35. https://doi.org/10.1096/fj.08-109306
Rabaneda LG, et al. 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-dependent Cyclin E Expression. FASEB J. 2008;22(11):3823-35. PubMed PMID: 18703672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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-dependent cyclin E expression. AU - Rabaneda,Luis G, AU - Carrasco,Manuel, AU - López-Toledano,Miguel A, AU - Murillo-Carretero,Maribel, AU - Ruiz,Félix A, AU - Estrada,Carmen, AU - Castro,Carmen, Y1 - 2008/08/14/ PY - 2008/8/16/pubmed PY - 2008/11/19/medline PY - 2008/8/16/entrez SP - 3823 EP - 35 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 22 IS - 11 N2 - Hyperhomocysteinemia (HHcy)-abnormally elevated plasma levels of homocysteine (Hcy)-has 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 in vitro and in vivo. We show that Hcy exerts an antiproliferative effect on basic fibroblast growth factor (bFGF) -stimulated NPCs isolated from the postnatal subventricular zone (SVZ), accompanied by inactivation of the extracellular signal-regulated kinase (Erk1/2) and inhibition of Erk1/2-dependent 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-responsive progenitors already committed to a neuronal phenotype, our results strongly suggest that excess Hcy inhibits neurogenesis in the DG and SVZ by inhibiting the bFGF-dependent activation of Erk1/2 in these cells. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/18703672/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_dependent_cyclin_E_expression_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.08-109306?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -