EXPRESSION OF THE GENES FOR ALPHA-TYPE AND BETA-TYPE CALCITONIN-GENE-RELATED PEPTIDE DURING POSTNATAL RAT-BRAIN DEVELOPMENT

In this study we have analysed the expression of the genes for both al pha-type and beta-type calcitonin gene-related peptide (CGRP) during p ostnatal development of the rat brain and compared it with the express ion of CGRP-like immunoreactivity. At birth both alpha-type and beta-t ype CGRP messenger RNA were present in the parabrachial nucleus, infer ior olive and motor nuclei (except for abducens nucleus), and only alp ha-type CGRP messenger RNA in some posterior thalamic nuclei. As devel opment advanced, new nuclei started to express either only alpha-CGRP gene (superior olive, parabigeminal, sagulum, and some hypothalamic an d cranial thalamic nuclei) or both genes (abducens nucleus). In the in ferior olive both genes were transiently expressed. beta-CGRP messenge r RNA disappeared by postnatal day 10 and alpha-CGRP messenger RNA by postnatal day 20. During the whole postnatal development beta-CGRP gen e expression predominated over that of alpha-CGRP in the trigeminal an d eve motor nuclei, while in the remainder nuclei alpha-CGRP messenger RNA was either the predominant isoform or the sole one. CGRP-like imm unoreactivity, which does not distinguish between alpha-type and beta- type CGRP, was detected in those nuclei containing either alpha-CGRP m essenger RNA or beta-CGRP messenger RNA. However, no CGRP messenger RN A was detected in areas such as superior colliculus, lateral pontine n ucleus, 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 transientl y detected by postnatal day 5 in some cells of the globus pallidus. In the adult brain, the levels of alpha- and beta-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 fa ctor. The transient expression in neurons of the inferior olive, match ing the period when climbing fibres and cerebellar cortex are developi ng, seems to support such an idea. The results of this study show that those nuclei expressing beta-CGRP gene also express alpha-CGRP gene. However, there are a number of nuclei that only express alpha-CGRP gen e. On the other hand, CGRP-like immunoreactivity is detected in some n uclei which express no CGRP messenger RNA. It suggests that such nucle i express any CGRP-related protein (identified by the antibodies again st CGRP) or, if they really contain CGRP protein, this is produced fro m undetectable amounts (using our in situ hybridization histochemistry procedure) of CGRP messenger RNA or it comes from other nuclei that c onnect with them in which CGRP protein is synthesized and then transfe rred. (C) 1997 IBRO. Published by Elsevier Science Ltd.