Oxygen-glucose Deprivation Induces The Pathological Changes Of Neurites In Cultured Hippocampal Neurons

Alzheimer's disease(AD) is the most common type of senile dementia, of which the neuronal degeneration is the main feature in the central nervous system. AD patients present with progressive cognitive impairment, memory loss and loss of intellectual ability, and ultimately, without ability to take care of themselves. Consequently, such conditions not only results in the patient's family suffering, but also causes heavy pressure on whole society. The two obvious neuropatholopgical changes in AD are senile plaques(SP) and neurofibrillary tangles(NFT). Up to date, the pathogenesis of AD is still unclear and there is no effective treatment. In recent years, research findings suggest that axonopathy may play an important role in the pathogenesis of AD, and that the characteristic changes of axonopathy including the swollen axons and varicosities, axonal transport impairment and axonal leakage may be involved in the origin and formation of SP and NFT. Recent studies in animal models have demonstrated that AD-related risk factors such as cerebral ischemia, brain damage, oxidative stress and diabetic encephalopathy may lead to “neuritepathy”(axonaopathy and dendropathy). To further clarify the importance of “neuritepathy” in the pathogenesis of AD in relation to the ADassociated risk factors, we investigated the effects of oxygen-glucose deprivation(OGD) combining with oxygen-glucose reapplication for 24 h on the neurites of primary cultured hippocampal neurons.OGD treatments in different periods(0.5h, 1h, 2h or 4h) followed by oxygenglucose reapplication for 24 h were carried out in rat hippocampal neurons cultured for 8 days. The neuronal morphology(somas and neurites), the transport function and the distribution of mitochondria in neurites were real-time observed and imaged with a cell workstation, and further measurement and analysis were also carried out. The results showed that:(1) a short time(0.5h and 1h) OGD treatment combing with 24 h oxygenglucose reapplication had no obvious influence on the neuronal morphology; a relative long-time(2h) treatment together with 24 h oxygen-glucose reapplication resulted in vacuolar changes of cell bodies and neuritic degeneration in some neurons, while a long-time(4h) OGD treatment followed by 24 h oxygen-glucose reapplication induced necrotic changes in most neurons accompanied with the neuritic fracture and disintegration;(2) anterograde and retrograde transport of neurites was significantly decreased after OGD treatment and even stopped after a longer time treatment;(3) 2h OGD treatment followed by 24 h oxygen-glucose reapplication leaded to abnormal distribution and aggregation of neuritic mitochondria.These results suggest that OGD treatemnet combing with oxygen-glucose reapplication could lead to the structural and functional changes of neurites in the cultured hippocampal neurons. Our findings may provide important experimental evidence for elucidating the role of cerebral vascular disease and stroke in the pathogenesis of AD.