Effects of lithium and deafferentation on expression of glycogen synthase kinase-3beta, NFkappaB, beta-catenin and pCreb in the chick cochlear nucleus.
The avian brainstem serves as a useful model to answer the question of how afferent activity influences the viability of target neurons. Approximately 20-30% of neurons in the avian cochlear nucleus, nucleus magnocellularis (NM) die following deafferentation (i.e., deafness produced by cochlea removal). Interestingly, Bcl-2 mRNA (but not protein) is upregulated in 20-30% of NM neurons following deafferentation. We have recently shown that chronic treatments of lithium upregulates the neuroprotective protein Bcl-2 and increases neuronal survival following deafferentation. The pathways leading to the upregulation of Bcl-2 expression following these two manipulations are unknown. The present experiments examine changes in glycogen synthase kinase-3 beta (Gsk-3beta), and transcription factors nuclear factor kappaB (NFkappaB), beta-catenin, and pCreb following lithium administration and following deafferentation. These molecules are known to be influenced by lithium and to regulate Bcl-2 expression in other model systems. Lithium decreased immunolabeling for Gsk-3beta and increased expression for all three transcription factors. Deafferentation, however, did not alter Gsk-3beta or NFkappaB, resulted in lower beta-catenin expression, but did increase pCreb immunoreactivity. While it is possible that pCreb is a common link in the regulation of Bcl-2 following these two manipulations, the timing and distribution of pCreb labeling suggests that it is not the sole determinant of Bcl-2 upregulation following deafferentation. It is likely that the regulation of Bcl-2 gene expression by lithium and by deafferentation involves different molecular pathways.
Bush
Angela L
AL
Department of Psychology, Program in Neuroscience, Florida State University, Tallahassee, FL 32306-1270, USA.
Hyson
Richard L
RL
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D050882:CREB-Binding Protein / Q000378:metabolism*; D002645:Chickens; D017626:Cochlear Nucleus / Q000187:drug effects* / Q000378:metabolism; D003714:Denervation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D038341:Glycogen Synthase Kinases / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D051176:beta Catenin; D050882:CREB-Binding Protein; D038341:Glycogen Synthase Kinases; D018021:Lithium Chloride