Distribution of the stress protein HSP70 in the cerebellum of patients with schizophrenia

Makris Leonidas PhD

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.

This study (as all post mortem studies) offers very limited insight into the time course by which the synaptic alterations, concerning HSP70, develop in schizophrenia.

The present study showed the dysfunction of synapses in the cerebellar glomeruli of the granular layer, in patients with schizophrenia, by reduced levels or absence of HSP70. These results suggest that the reduced levels of HSP70 in the cerebellum are likely to contribute synergistically to the cognitive dysfunction in schizophrenia.

This finding supports: a) the synaptic pathology and b) abnormality of neuroprotective mechanisms in neuronal networks of the cerebellum in schizophrenia.