W. Darmanto et al., Derangement of Purkinje cells in the rat cerebellum following prenatal exposure to X-irradiation: Decreased reelin level is a possible cause, J NE EXP NE, 59(3), 2000, pp. 251-262
Citations number
27
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
It has been reported that prenatal X-irradiation of rats during the late ge
station period causes heterotopic Purkinje cells in the internal granular l
ayer (IGL) of the abnormally foliated cerebellum. The present study was des
igned to demonstrate the process of X-ray-induced derangement of Purkinje c
ells and their surrounding cells. In addition, the expression of some morph
oregulatory molecules was examined to determine which molecules are involve
d in the abnormal pattern of Purkinje cells. Pregnant rats (n = 22) were ex
posed to 2.5 Gy X-radiation on gestation day 21 and the cerebellum of proge
ny was examined histologically and by immunohistochemistry to identify Purk
inje and Bergmann cells. At 12 h after exposure, extensive cell death was o
bserved in the external granular layer (EGL). By postnatal day (P) 9, while
Purkinje cells with well-developed dendrites aligned underneath the EGL in
the control cerebellum, Purkinje cells with shorter and abnormally oriente
d dendrites failed to align and remained in the heterotopic location in the
IGL. Bergmann cells and their fibers were also disoriented but later recov
ered in their proper position. Abnormal folia developed in the irradiated r
ats. Using immunohistochemistry, we next examined the levels of the neural
cell adhesion molecule (NCAM), fibronectin, tenascin, and Reelin. Among the
m, only the level of Reelin was affected significantly. Reelin decreased st
rikingly in the premigratory zone of the EGL and IGL in the irradiated cere
bellum on P1, and dr decrease continued until P9. Decreased Reelin expressi
on was demonstrated quantitatively by Northern blot analysis and the correl
ation between the mRNA and protein levels was well presented. The expressio
n of reelin mRNA decreased significantly by irradiation from PO, bring almo
st one third of the level in controls on P4, and tended to recover up to P9
. It is thus indicated that X-irradiation causes a marked decrease in the l
evel of Reelin at the critical stage for the alignment of Purkinje cells. S
ince Reelin has been shown to play an important role in the migration of ne
ural cells, it is suggested that the decrease in Reelin by X-irradiation is
an important factor for the derangement of Purkinje cells.