Congenital blindness does not protect against a schizophrenia-related phenotype in rodents

先天性失明无法预防啮齿动物的精神分裂症相关表型

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作者:Stephanie M Perez, Hannah B Elam, Alexandra M McCoy, Angela M Boley, Nicole E Eassa, Daniel J Lodge

Background

In 1950, Drs. Chevigny and Braverman authored a book about people's attitudes and prejudices toward the blind, noting that out of the thousands of schizophrenia patients they and others had treated, not one was blind. This led some to the intriguing hypothesis that congenital blindness may provide protection against schizophrenia. In this study, we directly examined whether congenital blindness protects against a schizophrenia-related phenotype in the methylazoxymethanol acetate (MAM) rodent model. Design: Enucleation surgeries were performed on pups of MAM- or saline-treated rats on post-natal day 10. Once pups reached adulthood, male and female rats were evaluated for schizophrenia-like phenotypes using behavioral and electrophysiological measures. Consistent with previous work, MAM-treated rats display elevated dopamine neuron population activity, deficits in pre-pulse inhibition of startle, and hypersensitivity to psychomotor stimulants.

Conclusions

Alterations in dopamine neuron activity and associated behaviors observed in blind rats are likely secondary to aberrant circadian regulation. This is the first preclinical study examining whether congenital blindness protects against a schizophrenia-like phenotype. While support of this hypothesis would have led to novel avenues of research and potential novel therapies, the results of current study suggest that blindness does not protect against schizophrenia.

Results

Blindness did not protect against any of the MAM-induced phenotypes. Surprisingly, blindness in saline-treated rats caused changes in behavior and dopamine neuron activity. To examine the circadian rhythms of enucleated rats, we performed non-invasive measurements of corticosterone, a steroid hormone known to vary across the light/dark period, revealing blind rats display aberrant (non-cycling) corticosterone levels. Conclusions: Alterations in dopamine neuron activity and associated behaviors observed in blind rats are likely secondary to aberrant circadian regulation. This is the first preclinical study examining whether congenital blindness protects against a schizophrenia-like phenotype. While support of this hypothesis would have led to novel avenues of research and potential novel therapies, the results of current study suggest that blindness does not protect against schizophrenia.

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