Gene expression profiling and cellular distribution of molecules with altered expression in the hippocampal CA1 region after developmental exposure to anti-thyroid agents in rats.
To determine whether developmental hypothyroidism causes permanent disruption of neuronal development, we first performed a global gene expression profiling study targeting hippocampal CA1 neurons in male rats at the end of maternal exposure to anti-thyroid agents on weaning (postnatal day 20). As a result, genes associated with nervous system development, zinc ion binding, apoptosis and cell adhesion were commonly up- or down-regulated. Genes related to calcium ion binding were up-regulated and those for myelination were often down-regulated. We, then, examined immunohistochemical cellular distribution of Ephrin type A receptor 5 (EphA5) and Tachykinin receptor (Tacr)-3, those selected based on the gene expression profiles, in the hippocampal formation at the adult stage (11-week-old) as well as at the end of exposure. At weaning, both EphA5- and Tacr3-immunoreactive cells with strong intensities appeared in the pyramidal cell layer or stratum oriens of the hippocampal CA1 region. Although the magnitude of the change was decreased at the adult stage, Tacr3 in the CA1 region showed a sustained increase in expressing cells until the adult stage after developmental hypothyroidism. On the other hand, EphA5-expressing cells did not show sustained increase at the adult stage. The results suggest that developmental hypothyroidism caused sustained neuronal expression of Tacr3 in the hippocampal CA1 region, probably reflecting a neuroprotective mechanism for mismigration.
Saegusa
Yukie
Y
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Woo
Gye-Hyeong
GH
Fujimoto
Hitoshi
H
Inoue
Kaoru
K
Takahashi
Miwa
M
Hirose
Masao
M
Igarashi
Katsuhide
K
Kanno
Jun
J
Mitsumori
Kunitoshi
K
Nishikawa
Akiyoshi
A
Shibutani
Makoto
M
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D003409:Congenital Hypothyroidism / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D007150:Immunohistochemistry; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008713:Methimazole / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011441:Propylthiouracil / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D036123:Receptor, EphA5 / Q000235:genetics / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric
D018039:Receptors, Tachykinin; D008713:Methimazole; D011441:Propylthiouracil; D036123:Receptor, EphA5