A. Kinnunen et al., IN-SITU DETECTION OF H1-RECEPTOR MESSENGER-RNA AND ABSENCE OF APOPTOSIS IN THE TRANSIENT HISTAMINE SYSTEM OF THE EMBRYONIC RAT-BRAIN, Journal of comparative neurology, 394(1), 1998, pp. 127-137
In the developing brain, histamine is one of the first neurotransmitte
rs to appear. The concentration of histamine in the prenatal brain is
fivefold that of adult levels. During the prenatal development a large
transiently histamine-immunoreactive cell population distinct from th
e adult histaminergic system can be found within a subpopulation of th
e developing serotonergic raphe nuclei neurons. Also histamine-immunor
eactive nerve fibers are widely distributed already during the prenata
l development extending to the diencephalon, the thalamus, the cortex,
and the spinal cord. Large numbers of histamine-containing mast cells
also migrate into the brain during the late prenatal life. The wide d
istribution and high prenatal concentrations imply important functions
for the histaminergic system during intrauterine development. However
, little is known about the actual functions of histamine during devel
opment, and which of the histamine receptors are present in the prenat
al rat brain is currently unknown. In the present study, we used in si
tu hybridization to study the distribution of H1-receptor (H1R) mRNA i
n the embryonic rat brain and spinal cord. H1R mRNA could be detected
in rat brain and in spinal cord on embryonic day (E) 14, and the expre
ssion pattern seemed to partially localize in areas containing histami
ne-immunoreactive nerve fibers through E14-E20. H1R mRNA was also dete
cted by reverse transcriptase polymerase chain reaction from embryonic
brain samples and by Northern hybridization. The possible involvement
of apoptosis in the disappearance of the developing transiently hista
minergic system was studied by using apoptosis detection based on the
terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immun
ostaining. Although histamine immunoreactivity disappears dramatically
from the developing raphe nuclei after E18, only occasional apoptotic
nuclei could be seen in the histamine-immunoreactive cell bodies. The
presence of H1R mRNA during the embryonic development renders it poss
ible that histamine could exert an H1R-specific function at the time o
f the embryonic histamine peak. (C) 1998 Wiley-Liss, Inc.