Cellular distribution and developmental expression of AMP-activated protein kinase isoforms in mouse central nervous system

The mammalian AMP-activated protein kinase is a heterotrimeric serine/threo nine protein kinase with multiple isoforms for each subunit (alpha, beta, a nd gamma) and is activated under conditions of metabolic stress. It is wide ly expressed in many tissues, including the brain, although its expression pattern throughout the CNS is unknown. We show that brain mRNA levels for t he alpha 2 and beta 2 subunits were increased between embryonic days 10 and 14, whereas expression of alpha 1, beta 1, and gamma 1 subunits was consis tent at all ages examined. Immunostaining revealed a mainly neuronal distri bution of all isoforms. The alpha 2 catalytic subunit was highly expressed in neurons and activated astrocytes, whereas the alpha 1 catalytic subunit showed low expression in neuropil. The gamma 1 noncatalytic subunit was hig hly expressed by neurons, but not by astrocytes. Expression of the beta 1 a nd beta 2 noncatalytic subunits varied, but some neurons, such as granule c ells of olfactory bulb, did not express detectable levels of either beta is oform. Preferential nuclear localization of the alpha 2, beta 1, and gamma 1 subunits suggests new functions of the AMP-activated protein kinase, and the different expression patterns and cellular localization between the two catalytic subunits alpha 1 and alpha 2 point to different physiological ro les.