title: Neuroprotective role of liver growth factor "LGF" in an experimental model of cerebellar ataxia.
abstract: Cerebellar ataxias (CA) comprise a heterogeneous group of neurodegenerative diseases characterized by a lack of motor coordination. They are caused by disturbances in the cerebellum and its associated circuitries, so the major therapeutic goal is to correct cerebellar dysfunction. Neurotrophic factors enhance the survival and differentiation of selected types of neurons. Liver growth factor (LGF) is a hepatic mitogen that shows biological activity in neuroregenerative therapies. We investigate the potential therapeutic activity of LGF in the 3-acetylpiridine (3-AP) rat model of CA. This model of CA consists in the lesion of the inferior olive-induced by 3-AP (40 mg/kg). Ataxic rats were treated with 5 µg/rat LGF or vehicle during 3 weeks, analyzing: (a) motor coordination by using the rota-rod test; and (b) the immunohistochemical and biochemical evolution of several parameters related with the olivo-cerebellar function. Motor coordination improved in 3-AP-lesioned rats that received LGF treatment. LGF up-regulated NeuN and Bcl-2 protein levels in the brainstem, and increased calbindin expression and the number of neurons receiving calbindin-positive projections in the cerebellum. LGF also reduced extracellular glutamate and GABA concentrations and microglia activation in the cerebellum. In view of these results, we propose LGF as a potential therapeutic agent in cerebellar ataxias.
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain. luciacalatrava@gmail.com.
authors.forename: Lucía
authors.initials: L
authors.lastname: Calatrava-Ferreras
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain. rafael.gonzalo@hrc.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gonzalo-Gobernado
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain. diana.reimers@hrc.es.
authors.forename: Diana
authors.initials: D
authors.lastname: Reimers
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain. antonio.sanchez@hrc.es.
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Herranz
authors.affiliation: Service of Neurology, Ramón y Cajal Hospital, Madrid 28034, Spain. jimeneze@yahoo.com.
authors.forename: Adriano
authors.initials: A
authors.lastname: Jiménez-Escrig
authors.affiliation: Service of Experimental Biochemistry, Puerta de Hierro-Majadahonda Hospital, Madrid 28222, Spain. jjdiazgil@yahoo.es.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Díaz-Gil
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain. m.jose.casarejos@hrc.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Casarejos
authors.affiliation: Service of Biochemistry, Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid 28034, Spain. teresa.montero@hrc.es.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Montero-Vega
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain. eulalia.bazan@hrc.es.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Bazán
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001663:Bilirubin / Q000494:pharmacology*; D064026:Calbindins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002524:Cerebellar Ataxia / Q000188:drug therapy* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D064026:Calbindins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; C546339:Rbfox3 protein, rat; D012709:Serum Albumin; C053498:albumin-bilirubin complex; C010835:3-acetylpyridine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001663:Bilirubin; D000075462:Serum Albumin, Human