TY - JOUR
T1 - Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains
AU - Taniguchi, Hidetoshi
AU - Mohri, Ikuko
AU - Okabe-Arahori, Hitomi
AU - Kanekiyo, Takahisa
AU - Kagitani-Shimono, Kuriko
AU - Wada, Kazuko
AU - Urade, Yoshihiro
AU - Nakayama, Masahiro
AU - Ozono, Keiichi
AU - Taniike, Masako
N1 - Funding Information:
We thank Dr. Keiko Matsuoka for preparing autopsy samples and Dr. Nanae Nagata for technical assistance. This study was supported by a grant (No. 17591085, to M.T. and 18591218 to K.W.) from the program Grants-in-aid for Scientific Research (C) of the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by grants from Mitsubishi Foundation (to Y.U.), Japan Foundation for Applied Enzymology (to I.M and to Y.U.), Japan Aerospace Exploration Agency (to Y.U.), Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO; to Y.U.) and Osaka City (to Y.U.).
PY - 2007/6/8
Y1 - 2007/6/8
N2 - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM1 and GM2 gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24 h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1 h after reoxygenation and that it decreased to the normal level by 24 h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain.
AB - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM1 and GM2 gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24 h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1 h after reoxygenation and that it decreased to the normal level by 24 h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain.
KW - Apoptosis
KW - Hypoxic-ischemic encephalopathy
KW - Lipocalin-type prostaglandin D synthase
KW - Neonate
KW - Prostaglandin D
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U2 - 10.1016/j.neulet.2007.04.016
DO - 10.1016/j.neulet.2007.04.016
M3 - Article
C2 - 17499437
AN - SCOPUS:34248667307
SN - 0304-3940
VL - 420
SP - 39
EP - 44
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -