Abstract
Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders.
Highlights
Cerebellar ataxias (CAs) include a heterogeneous group of infrequent diseases characterized by lack of motor coordination [1]
HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats
We show that HuUCBMCs upregulate the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP-lesioned rats
Summary
Cerebellar ataxias (CAs) include a heterogeneous group of infrequent diseases characterized by lack of motor coordination [1]. According to their etiology, they can be divided into sporadic forms and hereditary diseases. Current therapeutic approaches are based on the use of drugs that correct some of the molecular processes involved in the pathogenesis of this group of diseases [1, 6,7,8]. Other studies have assayed the potential therapeutic activity of intracerebroventricular, peripheral, or intranasal administration of neurotrophic factors such as insulinlike growth factor (IGF-I), or glial-derived growth factor (GDNF), in different experimental models of cerebellar ataxia in rodents [9,10,11,12,13]. The above-mentioned treatments (drugs and trophic factors) yielded promising results, there is not yet an effective therapy for these types of diseases to date [1]
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