Expression of the genes for α-type and β-type calcitonin gene-related peptide during postnatal rat brain development

Abstract

In this study we have analysed the expression of the genes for both α-type and β-type calcitonin gene-related peptide (CGRP) during postnatal development of the rat brain and compared it with the expression of CGRP-like immunoreactivity. At birth both α-type and β-type CGRP messenger RNA were present in the parabrachial nucleus, inferior olive and motor nuclei (except for abducens nucleus), and only α-type CGRP messenger RNA in some posterior thalamic nuclei. As development advanced, new nuclei started to express either only α-CGRP gene (superior olive, parabigeminal, sagulum, and some hypothalamic and cranial thalamic nuclei) or both genes (abducens nucleus). In the inferior olive both genes were transiently expressed. β-CGRP messenger RNA disappeared by postnatal day 10 and α-CGRP messenger RNA by postnatal day 20. During the whole postnatal development β-CGRP gene expression predominated over that of α-CGRP in the trigeminal and eye motor nuclei, while in the remainder nuclei α-CGRP messenger RNA was either the predominant isoform or the sole one. CGRP-like immunoreactivity, which does not distinguish between α-type and β-type CGRP, was detected in those nuclei containing either α-CGRP messenger RNA or β-CGRP messenger RNA. However, no CGRP messenger RNA was detected in areas such as superior colliculus, lateral pontine nucleus, pars reticulata of the substantia nigra, perifornical area, or zona incerta in which CGRP-like immunoreactivity was prominent. CGRP-like immunoreactivity, but not CGRP messenger RNA, was also transiently detected by postnatal day 5 in some cells of the globus pallidus. In the adult brain, the levels of α- and β-CGRP messenger RNA as well as those of CGRP-like immunoreactivity were considerably reduced. This fact, similar to that of other growth- and development-associated factors, suggests a role for CGRP as a neuron-derived neurotrophic factor. The transient expression in neurons of the inferior olive, matching the period when climbing fibres and cerebellar cortex are developing, seems to support such an idea. The results of this study show that those nuclei expressing β-CGRP gene also express α-CGRP gene. However, there are a number of nuclei that only express α-CGRP gene. On the other hand, CGRP-like immunoreactivity is detected in some nuclei which express no CGRP messenger RNA. It suggests that such nuclei express any CGRP-related protein (identified by the antibodies against CGRP) or, if they really contain CGRP protein, this is produced from undetectable amounts (using our in situ hybridization histochemistry procedure) of CGRP messenger RNA or it comes from other nuclei that connect with them in which CGRP protein is synthesized and then transferred.