Effects of Tumour Necrosis Factor-alpha on Developing Cerebellar Granule and Purkinje Neurons In Vitro

Abstract

Tumour necrosis factor-alpha (TNF-alpha) has been widely implicated in both neurodevelopment and neurodegeneration, yet its effects on individual populations of cerebellar neurons as they develop have not been fully elucidated. Therefore, we established primary neuronal cultures of developing murine cerebellar Purkinje neurons and postnatal cerebellar granule cells to determine the consequences of TNF-alpha exposure for their survival. We discovered that TNF-alpha did not affect the viability of cerebellar granule neurons at any of the ages studied, even though TNF-alpha and its receptors, TNFR1 and TNFR2, are widely expressed in the postnatal cerebellum. In addition, TNF-alpha was neither able to ameliorate, nor enhance, cell death in cerebellar granule cells elicited by a variety of stimuli including homocysteine and alcohol exposure. In contrast, in cultures established at embryonic day 16, TNF-alpha enhanced the number of cerebellar Purkinje neurons in vitro but this effect was not observed in embryonic day 19 cultures. Thus, TNF-alpha has differential and highly specific effects on different populations of cerebellar neurons as they develop.