The Distribution of the Stress Protein HSP70 in the Cerebellum of Patients with Schizophrenia
- 1 Theodor Theohari Cozzika Foundation, Neurobiology Research Institute, Athens, Greece.
Abstract
Data accumulated from neuro-imaging, clinical and morphological studies suggest that the cerebellum is involved in cognitive functions and thus may be important in the etiopathogenesis of schizophrenia, since patients show cognitive abnormalities. In the present study, we have attempted to localize cellular metabolic dysfunctions applying the immunohistochemical and Western blot method to demonstrate the expression of the stress protein HSP70, which is a marker of cellular metabolic dysfunction in the brain. We studied the post mortem brains’ cerebellum of 12 normal controls and 10 schizophrenics. We have used the polyclonal antibody rabbit anti-HSP70 on paraffin sections as well as on nitrocellulose membranes. Bound antibody was detected using the indirect method of streptavidin-peroxidase-DAB. The results in the cerebellum of controls showed intense HSP70 immunoreaction in the synaptic glomeruli of the granular cell layer, in the cytoplasm and dendrites of Purkinje cells. In the same areas of the cerebellum of schizophrenics the HSP70 immunoreactivity was minimal. These results suggest that the reduced levels of HSP70 in the cerebellum are likely to contribute synergistically to the cognitive dysfunction in schizophrenia. This may suggest abnormality of protective neural mechanisms in such pathological conditions.
- N. C. Andreasen, “A Unitary Model of Schizophrenia,” Archives of General Psychiatry, Vol. 56, No. 9, 1999, pp. 781-787. doi:10.1001/archpsyc.56.9.781
- H. Picard, I. Amado, S. Mouchet-Mages, J. P. Olie and M. O. Krebs, “The Role of the Cerebellum in Schizophrenia: An Update of Clinical, Cognitive, and Functional Evidences,” Schizophrenia Bulletin, Vol. 34, No. 1, 2008, pp. 155-172. doi:10.1093/schbul/sbm049
- D. O. Frost, C. A. Tamminga, D. R. Medoff, C. Caviness, G. Innocenti and W. T. Carpenter, “Neuroplasticity and Schizophrenia,” Biological Psychiatry, Vol. 56, No. 8, 2004, pp. 540-543. doi:10.1016/j.biopsych.2004.01.020
- S. L. Eastwood and P. J. Harrison, “Synaptic Pathology in the Anterior Cingulate Cortex in Schizophrenia and mood disorders. A review and A Western Blot Study of Synaptophysin, GAP-43 and the Complexins,” Brain Research Bulletin, Vol. 55, No. 5, 2001, pp. 569-578. doi:10.1016/S0361-9230(01)00530-5
- M. L. Phillips, W. C. Drevets, S. L. Rauch and R. Lane, “Neurobiology of Emotion Perception II: Implications for Major Psychiatric Disorders,” Biological Psychiatry, Vol. 54, No. 5, 2003, pp. 515-528. doi:10.1016/S0006-3223(03)00171-9
- A. Parcellier, S. Gurbuxani, E. Schmitt, E. Solary and C. Garrido “Heat Shock Proteins, Cellular Chaperones that Modulate Mitochondrial Cell Death Pathways,” Biochemical and Biophysical Research Communications, Vol. 304, No. 3, 2003, pp. 505-512. doi:10.1016/S0006-291X(03)00623-5
- R. G. Giffard and M. A. Yenari, “Many Mechanisms for Hsp70 Protection from Cerebral Ischemia,” Journal of Neurosurgical Anesthesiology, Vol. 16, No. 1, 2004, pp. 53-61. doi:10.1097/00008506-200401000-00010
- S. Takayama, J. C. Reed and S. Homma, “Heat-Shock Proteins as Regulators of Apoptosis,” Oncogene, Vol. 22, No. 56, 2003, pp. 9041-9047. doi:10.1038/sj.onc.1207114
- J. Q. Lan, J. Chen, F. R. Sharp, R. P. Simon and S. H. Graham, “Induction of Heat-Shock Protein (HSP72) in the Cingulated and Retrosplenial Cortex by Drugs that Antagonize the Effects of Excitatory Amino Acids,” Brain Research Molecular Brain Research, Vol. 46, No. 1-2, 1997, pp. 297-302. doi:10.1016/S0169-328X(97)00003-X
- H. Kluever and E. Barrera, “A Method for the Combined Stainning of Cells and Fibres in the Nervous System,” Journal of Neuropathology, Vol. 12, No. 4, 1953, pp. 400-403. doi:10.1097/00005072-195312040-00008
- J. L. Pongrac, F. A. Middleton, L. Peng, D. A. Lewis, P. Levitt and K. Mirnics, “Heat Shock Protein 12A Shows Reduced Expression in the Prefrontal Cortex of Subjects with Schizophrenia,” Biological Psychiatry, Vol. 56, No. 12, 2004, pp. 943-950. doi:10.1016/j.biopsych.2004.09.005