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 alpha-type and beta-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 alpha-type and beta-type CGRP messenger RNA were present in the parabrachial nucleus, inferior olive and motor nuclei (except for abducens nucleus), and only alpha-type CGRP messenger RNA in some posterior thalamic nuclei. As development advanced, new nuclei started to express either only alpha-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. Beta-CGRP messenger RNA disappeared by postnatal day 10 and alpha-CGRP messenger RNA by postnatal day 20. During the whole postnatal development beta-CGRP gene expression predominated over that of alpha-CGRP in the trigeminal and eye motor nuclei, while in the remainder nuclei alpha-CGRP messenger RNA was either the predominant isoform or the sole one. CGRP-like immunoreactivity, which does not distinguish between alpha-type and beta-type CGRP, was detected in those nuclei containing either alpha-CGRP messenger RNA or beta-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 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 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 beta-CGRP gene also express alpha-CGRP gene. However, there are a number of nuclei that only express alpha-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.
Terrado
J
J
Department of Anatomy, Embryology and Genetics, Faculty of Veterinary Sciences, University of Zaragoza, Spain.
Gerrikagoitia
I
I
Martinez-Millán
L
L
Pascual
F
F
Climent
S
S
Muniesa
P
P
Sarasa
M
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014158:Transcription, Genetic
D012333:RNA, Messenger; D015740:Calcitonin Gene-Related Peptide