Research ReportLocalization and spatiotemporal expression of IDO following transient forebrain ischemia in gerbils
Introduction
Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme for the tryptophan catabolism to kynurenine. IDO has long been of interest because it catabolizes l-tryptophan, leading to increases in the levels of metabolites, such as kynurenine and quinolinic acid (Saito et al., 1991). Growing evidence indicates that some of these metabolites are involved in the neurotoxicity associated with several brain disorders, such as Huntington's disease (Stoy et al., 2005), Parkinson's disease (Ogawa et al., 1992) and Alzheimer's disease (Guillemin and Brew, 2002), as well as in hepatic encephalopathy (Pearson and Reynolds, 1991) and glutaryl-CoA dehydrogenase deficiency (Heyes, 1987). However, the pathophysiology of the brain damage in these neurodegenerative disorders is not completely understood.
Transient cerebral ischemia initiates a process of cellular events that leads to delayed neuronal degeneration of several brain regions both in humans and in animal models (Pulsinelli et al., 1982, Petito and Pulsinelli, 1984, Horn and Schlote, 1992). Furthermore, a brief episode of ischemia causes “delayed neuronal death” in the CA1 sector of the hippocampus (Kirino, 1982). Accumulating evidence has indicated that the post-ischemic DNA fragmentation in the hippocampal CA1 area in experimental ischemic models is a key phenomenon for the delayed neuronal death, and is considered as apoptosis (Heron et al., 1993, Iwai et al., 1995, Hara et al., 1998a).
It has been reported that quinolinic acid and the kynurenine pathway enzyme, IDO were increased in several brain regions following transient forebrain ischemia (Saito et al., 1993a, Saito et al., 1993b). However, the specific brain localization of IDO has not yet been identified, in either normal brain or following transient forebrain ischemia. Of note, it has been reported that IDO is detectable only in microglia and astrocytes (Heyes et al., 1996), not in neurons (Schwarcz and Pellicciari, 2002), but more recently IDO has been reported as being present in human fetal neurons (Guillemin et al., 2005) and in murine neurons with upregulation in hippocampus by IFNγ (Roy et al., 2005). Thus, exact localization of IDO in central nervous system is still remains to be established. In the present study, we demonstrated the precise localization of IDO in normal gerbil brain by immunohistochemical detection, and secondly demonstrated the time-course changes of IDO following transient forebrain ischemia.
Section snippets
Localization of IDO by immunohistochemistry
IDO localization in normal gerbil brain was detected by immunohistochemistry. The expression areas of IDO were observed in normal thalamus (Figs. 1E and F), hypothalamus (Figs. 1I and J) and amygdaloid nucleus (Figs. 1K and L). However, IDO expressions were negative in the cingulate cortex (Figs. 1A and B), hippocampal CA1 sector (Figs. 1C and D) and parietal cortex (Figs. 1G and H).
Interestingly, time-dependent increase of IDO expression following transient ischemia was observed in CA1,
Discussion
The present immunohistochemical study showed that IDO staining was observed in thalamus, hypothalamus and amygdaloid nucleus of normal gerbil brain. The gerbil, which lacks posterior communication arteries necessary to complete the circle of Willis, commonly shows delayed neuronal death mainly in the CA2 pyramidal area of the hippocampus after 5 min of bilateral carotid occlusion (Kirino, 1982, Iwai et al., 1995).
Increased expression of IDO following transient forebrain ischemia was observed in
Animals
Male Mongolian gerbils, weighing 65–75 g, were subjected to severe forebrain ischemia as described previously (Hara et al., 1998b, Hara et al., 1999, Niwa et al., 1998). Briefly, the bilateral common carotid arteries were isolated through an anterior midcervical incision and occluded with microclips. After 5 min of forebrain ischemia, the clips were removed. Rectal temperatures were maintained at 37 ± 0.3 °C using a heating pad from the induction of anesthesia until 3 h following ischemia.
Acknowledgments
We would like to thank Kyoko Takahashi and Ayako Suga for their excellent technical assistance.
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Indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis
2014, Neuroscience LettersCitation Excerpt :However, more recently IDO has been reported as being present in human fetal neurons [15] and in murine hippocampal neurons, where levels are upregulated by interferon (IFN) [16]. We have reported that transient forebrain ischemia in gerbils produces tissue/cell-specific and time-dependent expressions of IDO in hippocampal CA1, cingulate cortex and hypothalamus, which was not related to glial cell activation [17]. Thus, exact localization of IDO in central nervous system still remains to be established.
PBN fails to suppress in delayed neuronal death of hippocampal CA1 injury following transient forebrain ischemia in gerbils
2012, Neuroscience LettersCitation Excerpt :Thus, the effects of PBN against delayed neuronal death are contradictory or species-dependent. Furthermore, we have shown that radical scavengers failed to reduce the neuronal injury following transient forebrain ischemia in gerbils [35]. Interestingly, it has been reported that oxidative damage contributes to neuronal injury in transient forebrain ischemia in gerbils [1].
Inflammatory stimuli reduce survival of serotonergic neurons and induce neuronal expression of indoleamine 2,3-dioxygenase in rat dorsal raphe nucleus organotypic brain slices
2011, NeuroscienceCitation Excerpt :Activation of IDO by for example, pro-inflammatory stimuli leads to depletion of tryptophan and to a reduced synthesis of serotonin in the brain, which may play a role in depression (Saito et al., 1991; Wichers and Maes, 2002). IDO is ubiquitously expressed in the brain and periphery (Potula et al., 2005; Roy et al., 2005; Guillemin et al., 2005a; Taguchi et al., 2008; Dai and Zhu, 2010), although the reports on cellular IDO expression are very divergent (Roy et al., 2005; Guillemin et al., 2005b). Here, we found a granular, cytoplasmic IDO staining in neurons, including expression in serotonergic neurons, but not in astrocytes or microglia.