Detection of bikunin mRNA in limited portions of rat brain

Takano, Masaoki; Mori, Yuichi; Shiraki, Hinako; Horie, Masato; Okamoto, Hiroshi; Narahara, Masanori; Miyake, Masanobu; Shikimi, Tadahiro

doi:10.1016/s0024-3205(99)00302-1

Cited by 13 publications

(20 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our observation of the presence of Ambp in mouse neurons is consistent with previous work by Takano, et. al (Takano et al, 1999). However, the presence of Ambp and Itih-1 and -4 in mouse neurons is in contrast to the work of Chan, et.…”

Section: Discussionmentioning

confidence: 99%

“…Inter-alpha Inhibitor Proteins (IAIPs) are a group of serine protease inhibitors that have been detected in many tissues including liver, intestine, kidney, stomach, placenta and brain signifying their diverse biological functions (Itoh et al, 1996, Daveau et al, 1998, Takano et al, 1999, Spasova et al, 2014). Although liver is the primary site of IAIPs synthesis and the major source of the IAIPs found in blood, our recent findings suggest that IAIPs are also present in brain and other organs during development (Spasova et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the information that is available regarding localization of IAIPs in CNS remains controversial. Some studies report the presence of the bikunin gene in neurons but not in astrocytes (Takano et al, 1999), whereas, others report bikunin immunoreactivity in astrocytes, but not in neurons (Yoshida et al, 1991a, Yoshida et al, 1994). Although we identified both the IaI and PaI proteins in the cerebral cortex of sheep (Spasova et al, 2014), more detailed information regarding the expression and localization of IAIPs in different cell types in the fetal and neonatal brain is lacking.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression and localization of Inter-alpha Inhibitors in rodent brain

et al. 2016

View full text Add to dashboard Cite

Inter-alpha Inhibitor Proteins (IAIPs) are a family of related serine protease inhibitors. IAIPs are important components of the systemic innate immune system. We have identified endogenous IAIPs in the central nervous system (CNS) of sheep during development and shown that treatment with IAIPs reduces neuronal cell death and improves behavioral outcomes in neonatal rats after hypoxic-ischemic brain injury. The presence of IAIPs in CNS along with their exogenous neuroprotective properties suggests that endogenous IAIPs could be part of the innate immune system in CNS. The purpose of this study was to characterize expression and localization of IAIPs in CNS. We examined cellular expressions of IAIPs in vitro in cultured cortical mouse neurons, in cultured rat neurons, microglia, and astrocytes, and in vivo on brain sections by immunohistochemistry from embryonic (E) day-18 mice and postnatal (P) day-10 rats. Cultured cortical mouse neurons expressed the light chain gene Ambp and heavy chain genes Itih-1, 2, 3, 4, and 5 mRNA transcripts and IAIPs proteins. IAIP proteins were detected by immunohistochemistry in cultured cells as well as brain sections from E18 mice and P10 rats. Immunoreactivity was found in neurons, microglia, astrocytes and oligodendroglia in multiple brain regions including cortex and hippocampus, as well as within both the ependyma and choroid plexus. Our findings suggest that IAIPs are endogenous proteins expressed in a wide variety of cell types and regions both in vitro and in vivo in rodent CNS. We speculate that endogenous IAIPs may represent endogenous neuroprotective immunomodulatory proteins within the CNS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and localization of Inter-alpha Inhibitors in rodent brain

et al. 2016

View full text Add to dashboard Cite

show abstract

“…A number of studies indicate that differences in developmental time course across brain regions and/or unique cellular properties ( e.g ., oligodendrocytes versus neurons) may contribute to differences in vulnerability that could account for the observed volume profiles (Andersen, 2003, Back, et al, 2002, Lodygensky, et al, 2011, Riddle, et al, 2012, Volpe, 2009). Furthermore, mRNA of bikunin, the light chain of IAIP, was localized to hippocampi and cerebral cortices in rats but not the striatum suggesting differential distribution across distinct brain regions (Takano, et al, 1999). How brain regional vulnerabilities or variations in the endogenous distribution of IAIPs, or related molecules, influence the effects of IAIP treatment is beyond the scope of the current study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the systemic link between IAIPs and inflammatory regulation following infection, IAIP related molecules and mRNA have been observed in neurons, astrocytes, and meningeal cells of the brain (Businaro, et al, 1992, Chan, et al, 1995, Daveau, et al, 1998, Kato, et al, 2001, Mizushima, et al, 1998, Sanchez, et al, 2002, Takano, et al, 1999, Werbowetski-Ogilvie, et al, 2006, Yoshida, et al, 1991). Recent evidence also demonstrates decreases in the Inter-alpha-Trypsin Inhibitor Heavy Chain 4 in the serum of human patients after acute ischemic stroke (Kashyap, et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes

Threlkeld

Gaudet

Rue

et al. 2014

Experimental Neurology

View full text Add to dashboard Cite

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, Inter-alpha Inhibitor Proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72 hours post insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72 hours following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that Inter-alpha Inhibitor Proteins may serve as novel therapeutics for brain injury associated with premature birth and/or neonatal brain injury and highlight the importance of assessing multiple ages, brain regions and behavioral domains when investigating experimental treatment efficacy.

show abstract

Ontogeny of inter‐alpha inhibitor protein (IAIP) expression in human brain

Kim

Monte

Hovanesian

et al. 2019

J of Neuroscience Research

View full text Add to dashboard Cite

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.

show abstract

Detection of bikunin mRNA in limited portions of rat brain

Cited by 13 publications

References 19 publications

Expression and localization of Inter-alpha Inhibitors in rodent brain

Expression and localization of Inter-alpha Inhibitors in rodent brain

Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes

Ontogeny of inter‐alpha inhibitor protein (IAIP) expression in human brain

Contact Info

Product

Resources

About