Neuroprotective Role of Liver Growth Factor “LGF” in an Experimental Model of Cerebellar Ataxia

International Journal of Molecular Sciences

Luc໚ Calatrava-Ferreras¹  Rafael Gonzalo-Gobernado¹  Diana Reimers¹  Antonio S. Herranz¹  Adriano Jiménez-Escrig²  Juan José D໚z-Gil³  Mar໚ José Casarejos¹  Mar໚ Teresa Montero-Vega⁴  Eulalia Bazán¹ 

[1] Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), Madrid 28034, Spain; E-Mails:;Service of Neurology, Ramón y Cajal Hospital, Madrid 28034, Spain; E-Mail:;Service of Experimental Biochemistry, Puerta de Hierro-Majadahonda Hospital, Madrid 28222, Spain; E-Mail:;Service of Biochemistry, Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid 28034, Spain; E-Mail:

关键词: liver growth factor;    neuroregeneration;    cerebellar ataxias;    neuroprotection;    glutamate;    GABA;   

DOI  :  10.3390/ijms151019056

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.