Histopathological and Behavioral Assessment of Toxin-Produced Cerebellar Lesion: A Potent Model for Cell Transplantation Studies in The Cerebellum


Mohammad Amin Edalatmanesh, Ph.D, 1,*Haniyeh Nikfarjam, M.Sc, 1Marzieh Moghadas, MSc, 1Aliakbar Haddad-Mashadrizeh, Ph.D, 2Reza Robati, M.Sc, 1Mohammad Reza Hashemzadeh, M.Sc, 3
Department of Physiology, Science and Research Branch, Islamic Azad University, Fars, Iran
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
Department of Stem cell and Regenerative Biology, Eram Biotechnology Research Center, Technical and Vocational Training Organization, Mashhad, Iran
Department of Physiology, Science and Research Branch, Islamic Azad University, Fars, Iran
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
Department of Stem cell and Regenerative Biology, Eram Biotechnology Research Center, Technical and Vocational Training Organization, Mashhad, Iran
*Corresponding Address: P.O.Box: 73715181 Department of Physiology Science and Research Branch Islamic Azad University Fars Iran Email:edalatmanesh@fsriau.ac.ir
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Edalatmanesh Mohammad Amin, Nikfarjam Haniyeh, Moghadas Marzieh, Haddad-Mashadrizeh Aliakbar, Robati Reza, Hashemzadeh Mohammad Reza. Histopathological and Behavioral Assessment of Toxin-Produced Cerebellar Lesion: A Potent Model for Cell Transplantation Studies in The Cerebellum. Cell J. 2014; 16(3): 325-334.

Abstract

Objective

The cerebellum is a key structure involved in coordinated motor planning, cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities.

Materials and Methods

In this experimental study, slow administration of quinolinic acid (QA, 5 µl of 200 µmol, 1 µl/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student’s t test.

Results

The QA treated group showed marked motor learning deficits on the rotating rod test (p=0.0001), locomotor asymmetry on the cylinder test (p=0.0001), dysmetria on the beam balance test (p=0.0001), abnormalities in neuromuscular strength on the hang wire test (p=0.0001), spatial memory deficits in the Morris water maze (MWM, p=0.001) and fear conditioned memory on the passive avoidance test (p=0.01) over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p=0.001) and granular cell density (p=0.0001) in the lesioned hemisphere of the cerebellum.

Conclusion

Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.