Increase in neurotrophin-3 expression followed by Purkinje cell degeneration in the adult rat cerebellum after spinal cord transection.

Changes in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) contents following thoracic spinal cord transection were investigated in the cerebral cortex, hippocampus, and cerebellum of rats. The NT-3 content became significantly elevated at 3 days after transection only in the cerebellum and gradually declined to the control level by 6 days after the injury, remaining unchanged in the cerebral cortex and hippocampus. No significant change in the BDNF content was observed in any of the regions tested. Immunohistochemical analysis showed that the labeling indicating NT-3-like immunoreactivity was intensified in both cerebellar granule and Purkinje cells 3 days after the injury. The number of Purkinje cells with aggregation of chromatin around the nuclear membrane and swelling of the cytoplasm and/or organelles gradually increased with time starting 4 days after the injury, demonstrating morphological changes indicative of necrosis. However, no abnormal morphology was found in cerebellar granule cells at any time examined. We suggest that it is reasonable that increased NT-3 stimulated the death of Purkinje cells, because 1) the degeneration was necrosis, which is known to be accelerated by neurotrophins under certain pathological conditions, and 2) the increase in NT-3 occurred prior to Purkinje cell degeneration. Therefore, our present results may imply that spinal cord injury-induced NT-3 accelerates injury rather than alleviates degeneration of Purkinje cells. Copyright 2000 Wiley-Liss, Inc.