Comparative distribution of myristoylated alanine-rich C kinase substrate (MARCKS) and F1/GAP-43 gene expression in the adult rat brain

Abstract

Myristoylated alanine-rich C-kinase substrate (MARCKS) and F1/GAP-43 (B-50/neuromodulin) are both major specific substrates for protein kinase C (PKC) and appear to play an important role in the regulation of neuroplastic events during development and in the adult brain. Since PKC isozymes are differentially expressed in brain and the expression of F1/GAP-43 and MARCKS are differentially regulated by PKC through posttranslational mechanisms, the present study examined the relative distribution of both mRNAs in the adult brain by using in situ hybridization histochemistry. MARCKS hybridization was most pronounced in the olfactory bulb, piriform cortex (layer II), medial habenular nucleus, subregions of the amygdala, specific hypothalamic nuclei, hippocampal granule cells, neocortex, and cerebellar cortex, intermediate in the superior colliculus, hippocampal CA1, and certain brainstem nuclei including the locus coeruleus, and low-absent in regions of the caudate-putamen, geniculate, thalamic nuclei, lateral habenular nucleus, and hippocampal CA3 pyramidal and hilar neurons. Consistent with previous reports, prominent F1/GAP-43 hybridization was observed in neocortex, medial geniculate, piriform cortex (layer II), substantia nigra pars compacta, hippocampal CA3 pyramidal cells, thalamic and hypothalamic nuclei, lateral habenular nucleus, locus coeruleus, raphe nuclei, and cerebellar granule cells, intermediate in regions of the thalamus, hypothalamus, and amygdala, and low-absent in regions of the olfactory bulb, caudate-putamen, medial habenular nucleus, hippocampal granule cells, and superior colliculus. Overall, F1/GAP-43 was highly expressed in a greater number of regions compared to MARCKS and, in a number of regions, including the hippocampus, habenular complex, ventral tegmentum, geniculate, and certain brain stem nuclei, a striking inverse pattern of expression was observed. These results indicate that MARCKS gene expression, like that of F1/GAP-43, remains elevated in select regions of the adult rat brain which are associated with a high degree of retained plasticity. The potential role of PKC in the regulation of MARCKS and F1/GAP-43 gene expression in brain is assessed.