Imaging and Spectral Characteristics of Amyloid Plaque Autofluorescence in Brain Slices from the APP/PS1 Mouse Model of Alzheimer's Disease / 神经科学通报·英文版

Amyloid deposits are one of the hallmark pathological lesions of Alzheimer's disease (AD). They can be visualized by thioflavin-S, silver impregnation, Congo red staining, and immunohistochemical reactions. However, that amyloid deposits generate blue autofluorescence (auto-F) has been ignored. Here, we report that visible light-induced auto-F of senile plaques (SPs) was detected and validated with conventional methods. Brain slices from APP/PS1 (amyloid precursor protein/presenilin 1) transgenic mice were mounted on slides, rinsed, coverslipped and observed for details of the imaging and spectral characteristics of the auto-F of SPs. Then the slices were treated with the above classic methods for comparative validation. We found that the SP auto-F was greatest under blue-violet excitation with a specific emission spectrum, and was much easier, more sensitive, and reliable than the classic methods. Because it does not damage slices, observation of auto-F can be combined with all post-staining techniques in slices and for brain-wide imaging in AD.

Accelerated and Exacerbated Effects of High Dietary Fat on Neuronal Damage Induced by Transient Cerebral Ischemia in the Gerbil Septum

BACKGROUND: Obesity induced by high-fat diet (HFD) is one of the most widespread metabolic disorders in current society. However, there has been little research regarding the effects of HFD-induced obesity in the septa of animal models of cerebral ischemia. Therefore, in the present study, we investigated septal effects of HFD on neuronal damage and gliosis induced by transient cerebral ischemia. METHODS: Body weight, blood glucose levels and serum lipid profiles levels were measured both in the normal diet (ND) and HFD-group. We also investigated the effects of ND and HFD on neuronal damage and gliosis in the septum after transient cerebral ischemia using immunohistochemistry. RESULTS: The levels of blood glucose, serum triglyceride, and total cholesterol were significantly increased in the HFD-fed gerbils compared with the ND-fed gerbils, although body weight was not significantly changed after HFD feeding. In the ND-fed gerbils, ischemia-induced neuronal damage was found in the septohippocampal nucleus (SHN) of the septum 7 days after ischemia. In the HFD-fed gerbils, ischemia-induced neuronal damage in the SHN was much more severe compared with that of the ND-fed gerbils 4 and 7 days after ischemia. In addition, we found that ischemia-induced glial activation including astrocytes and microglia was accelerated and exacerbated in the HFD-fed gerbils compared with that in the ND-fed gerbils. CONCLUSION: These results indicate that HFD can lead to much more severe effects in ischemia-induced neuronal damage/death in the septum after ischemia-reperfusion, and that it may be associated with accelerated change in glial activation.

Glia as a Link between Neuroinflammation and Neuropathic Pain

Contemporary studies illustrate that peripheral injuries activate glial components of the peripheral and central cellular circuitry. The subsequent release of glial stressors or activating signals contributes to neuropathic pain and neuroinflammation. Recent studies document the importance of glia in the development and persistence of neuropathic pain and neuroinflammation as a connecting link, thereby focusing attention on the glial pathology as the general underlying factor in essentially all age-related neurodegenerative diseases. There is wide agreement that excessive glial activation is a key process in nervous system disorders involving the release of strong pro-inflammatory cytokines, which can trigger worsening of multiple disease states. This review will briefly discuss the recent findings that have shed light on the molecular and cellular mechanisms of glia as a connecting link between neuropathic pain and neuroinflammation.

Curcumin Attenuates Glial Cell Activation But Cannot Suppress Hippocampal CA3 Neuronal Cell Death in i.c.v. Kanic Acid Injection Model

Kainic acid (KA) is a structural analogue of glutamate that interacts with specific presynaptic and postsynaptic receptors to potentiate the release and excitatory actions of glutamate. Systemic or intracerebroventricular (i.c.v.) administration of KA to experimental animals elicits multifocal seizures with a predominantly limbic localization, and results in neuronal death of cornu ammonia 1 (CA1), reactive gliosis and biochemical changes in the hippocampus and other limbic structures. Several lines of evidence suggest that reactive oxygen species (ROS) play a pivotal role in the pathogenesis of excitotoxic death by KA. Curcumin has been known to possess anti-oxidative and anti-inflammatory activities. In this study, the effects of curcumin on KA induced hippocampal cell death, reactive gliosis and biochemical changes in reactive glia were investigated by immunohistochemical methods. Our data demonstrated that curcumin attenuated KA-induced astroglial and microglial activation although it did not protect KA-induced hippocampal cell death.