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/threonine protein kinase with multiple isoforms for each subunit (alpha, beta, and gamma) and is activated under conditions of metabolic stress. It is widely expressed in many tissues, including the brain, although its expression pattern throughout the CNS is unknown. We show that brain mRNA levels for the 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 consistent at all ages examined. Immunostaining revealed a mainly neuronal distribution 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 highly expressed by neurons, but not by astrocytes. Expression of the beta 1 and beta 2 noncatalytic subunits varied, but some neurons, such as granule cells of olfactory bulb, did not express detectable levels of either beta isoform. 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 roles.