Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus

Abstract

The present immunohistochemical study provides evidence that the kynurenine pathway is up-regulated in Alzheimer's disease (AD) brain, leading to increases in the excitotoxin quinolinic acid (QUIN). We show that the regulatory enzyme of the pathway leading to QUIN synthesis, indoleamine 2,3 dioxygenase (IDO) is abundant in AD compared with controls. In AD hippocampus, both IDO- and QUIN-immunoreactivity (-IR) was detected in cortical microglia, astrocytes and neurones, with microglial and astrocytic expression of IDO and QUIN highest in the perimeter of senile plaques. QUIN-IR was present in granular deposits within the neuronal soma of AD cortex and was also seen uniformly labelling neurofibrillary tangles. Our data imply that QUIN may be involved in the complex and multifactorial cascade leading to neuro-degeneration in AD. These results may open a new therapeutic door for AD patients.

Characterization of the Kynurenine Pathway in Human Neurons

“…Although the factors determining the level of expression of kynurenine pathway enzymes in the intact brain remain to be clarified, the present work clearly indicates that a diverse range of neuronal types have the potential to produce these enzymes in the human brain. We previously showed that only a very low level of QUIN immunoreactivity is found in temporal neocortical and hippocampal areas in control brain tissue (Guillemin et al, 2005c) and that concentrations of QUIN in normal cerebral tissue are extremely low (Ͻ1 nM) (Guillemin et al, 2007). The present data are entirely consistent with our previous observations.…”

“…For this study, autopsy tissue was sampled from two neurologically normal male patients (39 and 64 years old), both with cardiac arrest as cause of death. Series of 45 m cryosections were processed for immunohistochemistry using the avidin-biotin complex detection system as described previously (Guillemin et al, 2005c). Freefloating sections were washed in 50% ethanol for 3 ϫ 15 min at 37°C and then incubated in 3% H 2 O 2 for 20 min to quench endogenous peroxidase activity.…”

The novel targets of DL-3-n-butylphthalide predicted by similarity ensemble approach in combination with molecular docking study

“…Besides that, it is also reported that excessively expressed IDO could lead to depression following ischemic stroke (10,11). Moreover, over-expressed IDO in hippocampus may also play a role as a pathological factor in Alzheimer disease (12). In the paper our team published in 2012, it has already been shown that NBP also exerts the therapeutic effect in vascular dementia (3), which may be partially explained by previously reported functions of IDO.…”

Increase in Alzheimer's related markers preceeds memory disturbances: Studies in vasopressin-deficient Brattleboro rat

“…Regarding AD pathomechanism post mortem immunocytochemistry in the hippocampus of AD patients revealed elevated TDO2 levels [21] and amyloid-β treatment increased TDO2 expression [22]. Thus, elevated TDO2 level in one year old rats might anticipate pathological changes.…”