Localization of the messenger RNA for the c-Jun NH2-terminal kinase kinase in the adult and developing rat brain: an in situ hybridization study.

ABSTRACT

Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates and activates stress-activated protein kinase/c-Jun NH2-terminal kinase, a recently discovered mitogen-activated protein kinase that is stimulated by stressful stimuli and that regulates cellular transcriptional activity. The distribution of the messenger RNA encoding for stress-activated protein kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult and developing rat central nervous system. In situ hybridization with a 35S-labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains. Specific labelling was generally associated with neuronal profiles. In the adult central nervous system, high hybridization signals were observed in the hippocampus, the granular layer of the cerebellum, the medial habenula, the anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus. Intermediate levels were present in diencephalic and mesencephalic regions and in the neocortex, while basal ganglia displayed a low hybridization signal. In the developing brain, the heterogeneous distribution of the hybridization signal observed in the adult brain was already present, but in the hippocampus and basal ganglia the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels were significantly higher at postnatal day 3 and during the second postnatal week than in the adult. The results show that stress-activated protein kinase/extracellular signal-regulated protein kinase-1 is widely expressed in the rat central nervous system and co-localizes with its substrate stress-activated protein kinase. The observed changes in stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels during postnatal development suggest a role for this protein in the maturation of brain circuits.