Developmental expression of Bcl-2 protein in human cortex

Apoptosis is essential for normal human neurodevelopment and is increasingly recognized for its role in various neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Bcl-2 is a 26 kDa membrane-associated protein known to protect neurons against apoptosis. Interestingly, Bcl-2 protein levels are altered in certain neurodegenerative disorders that reveal increased apoptosis. However, little is known about the normal expression of Bcl-2 protein in human brain. Bcl-2 protein levels were determined by ELISA and semiquantitative Western Blotting in the frontal cortex of 20 human post-mortem brains, separated into three groups: six infants (age: 0.83+/-1.0 years, mean+/-S.D.), five adolescents (age: 17.4+/-1.7 years), and nine adults (age: 41.0+/-9.6 years). All subjects died of non-CNS related illness and had no history of psychiatric illness. Bcl-2 increased significantly across the age groups in the ELISA (p=0.0058) and the Western Blot (p=0.002) experiments. The ELISA demonstrated significant differences in Bcl-2 levels between infant and adolescent cortex (p<0.05), and between infant and adult cortex (p<0.01) using a post-hoc Tukey's multiple comparison test. The Western blots demonstrated a similar significant increase in Bcl-2 between infant and adult cortex (p<0. 01). A secondary analysis showed significant correlation between individual ages and Bcl-2 levels (r(2)=0.4933, p=0.0006). This study demonstrates that Bcl-2 protein expression in human cortex is developmentally regulated and supports the hypothesis that Bcl-2 is involved in normal aging.