TY - JOUR
T1 - Ontogeny of inter-alpha inhibitor protein (IAIP) expression in human brain
AU - Kim, Boram
AU - De La Monte, Suzanne
AU - Hovanesian, Virginia
AU - Patra, Aparna
AU - Chen, Xiaodi
AU - Chen, Ray H.
AU - Miller, Miles C.
AU - Pinar, Mehmet Halit
AU - Lim, Yow Pin
AU - Stopa, Edward G.
AU - Stonestreet, Barbara S.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under the following award numbers: Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P30GM114750, National Institutes of Health 1R21NS095130, 1R21NS096525, and R44 NS084575-02. The authors assume all responsibility for the study and assert that the contents herein do not represent the National Institutes of Health's official views. We would like to dedicate this work to Edward G. Stopa, M.D., who was a superb neuropathologist, instrumental in this work, a true friend and key consultant to our laboratory. We also gratefully acknowledge the helpful editorial assistance of Kimberly Alonge, PhD.
Funding Information:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under the following award numbers: Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P30GM114750, National Institutes of Health 1R21NS095130, 1R21NS096525, and R44 NS084575‐02. The authors assume all responsibility for the study and assert that the contents herein do not represent the National Institutes of Health's official views. We would like to dedicate this work to Edward G. Stopa, M.D., who was a superb neuropathologist, instrumental in this work, a true friend and key consultant to our laboratory. We also gratefully acknowledge the helpful editorial assistance of Kimberly Alonge, PhD.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Inter-alpha inhibitor proteins (IAIPs) are naturally occurring immunomodulatory molecules found in most tissues. We have reported ontogenic changes in the expression of IAIPs in brain during development in sheep and abundant expression of IAIPs in fetal and neonatal rodent brain in a variety of cellular types and brain regions. Although a few studies identified bikunin, light chain of IAIPs, in adult human brain, the presence of the complete endogenous IAIP protein complex has not been reported in human brain. In this study, we examined the immunohistochemical expression of endogenous IAIPs in human cerebral cortex from early in development through the neonatal period and in adults using well-preserved postmortem brains. We examined total, nuclear, and cytoplasmic staining of endogenous IAIPs and their expression in neurofilament light polypeptide–positive neurons and glial fibrillary acidic protein (GFAP)–positive astrocytes. IAIPs were ubiquitously detected for the first time in cerebral cortical cells at 24–26, 27–28, 29–36, and 37–40 weeks of gestation and in adults. Quantitative analyses revealed that IAIPs were predominately localized in the nucleus in all age groups, but cytoplasmic IAIP expression was more abundant in adult than in the younger ages. Immunoreactivity of IAIPs was expressed in neurons and astrocytes in all age groups. In addition, IAIP co-localization with GFAP-positive astrocytes was more abundant in adults than in the developing brain. We conclude that IAIPs exhibit ubiquitous expression, and co-localize with neurons and astrocytes in the developing and adult human brain suggesting a potential role for IAIPs in development and endogenous neuroprotection.
AB - Inter-alpha inhibitor proteins (IAIPs) are naturally occurring immunomodulatory molecules found in most tissues. We have reported ontogenic changes in the expression of IAIPs in brain during development in sheep and abundant expression of IAIPs in fetal and neonatal rodent brain in a variety of cellular types and brain regions. Although a few studies identified bikunin, light chain of IAIPs, in adult human brain, the presence of the complete endogenous IAIP protein complex has not been reported in human brain. In this study, we examined the immunohistochemical expression of endogenous IAIPs in human cerebral cortex from early in development through the neonatal period and in adults using well-preserved postmortem brains. We examined total, nuclear, and cytoplasmic staining of endogenous IAIPs and their expression in neurofilament light polypeptide–positive neurons and glial fibrillary acidic protein (GFAP)–positive astrocytes. IAIPs were ubiquitously detected for the first time in cerebral cortical cells at 24–26, 27–28, 29–36, and 37–40 weeks of gestation and in adults. Quantitative analyses revealed that IAIPs were predominately localized in the nucleus in all age groups, but cytoplasmic IAIP expression was more abundant in adult than in the younger ages. Immunoreactivity of IAIPs was expressed in neurons and astrocytes in all age groups. In addition, IAIP co-localization with GFAP-positive astrocytes was more abundant in adults than in the developing brain. We conclude that IAIPs exhibit ubiquitous expression, and co-localize with neurons and astrocytes in the developing and adult human brain suggesting a potential role for IAIPs in development and endogenous neuroprotection.
KW - astrocytes
KW - brain development
KW - human autopsy
KW - immunohistochemistry
KW - inter-alpha inhibitors
KW - neurons
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U2 - 10.1002/jnr.24565
DO - 10.1002/jnr.24565
M3 - Article
C2 - 31797408
AN - SCOPUS:85076178434
SN - 0360-4012
VL - 98
SP - 869
EP - 887
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 5
ER -