Disorders of the Nervous System
Author: Benjamín Zylberberg | Email: BZylberberg-iimt@austral.edu.ar
Benjamín Zylberberg1°, Angela M. Suburo1°2°, M. Florencia Coronel1°2°, Graciela L. Mazzone1°2°
1° Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET-Universidad Austral, Av. Pte. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina.
2° Facultad de Ciencias Biomédicas, Universidad Austral, Av. Pte. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina.
We have previously demonstrated that excitotoxicity can be triggered by the glutamate analogue kainate (KA), leading to a significant decrease in the number of rat spinal neurons and a higher release of glutamate, ultimately resulting in the blockage of the locomotor network. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/C adult mice was induced by KA intraspinal injection (1 μL, 5 mM) while spinal cord in vitro excitotoxicity was produced by bath-applied KA (100 μM). Locomotor behaviors were evaluated in an open field by applying the Basso Mouse locomotor scale rating (BMS), the horizontal ladder, and the footprinting analysis. The application of KA induced a significant deterioration in hindlimb motor coordination and balance during locomotion. When performing the Choi test an increased sensitivity to cold stimuli was detected in the ipsilateral hindpaw from 8 to 30 days after injury. Immunohistochemical analysis showed that KA evoked significant neuronal loss and decreased the number of CREB positive nuclei in the ventral horn and dorsal layers III-IV. Thus, our present data suggests that CREB could be used as a novel indicator of spinal tissue damage. Supported by Universidad Austral, CONICET, FONCYT, and IBRO Collaborative Research Grant.