静脉注射免疫球蛋白疗法维持和保护原代大鼠海马神经元和原代人脑培养物并抵抗氧化损伤

Title:Intravenous Immunoglobulin Treatment Preserves and Protects Primary Rat Hippocampal Neurons and Primary Human Brain Cultures Against Oxidative Insults

Volume: 11 Issue: 7

Author(s): Debomoy K. Lahiri and Balmiki Ray

Affiliation:

关键词: 老化，脑，海马神经元，人类神经元，免疫球蛋白，神经保护，神经维持，神经救援，氧化应激，突触，突触蛋白

摘要: Alzheimer’s disease (AD) is characterized by deleterious accumulation of amyloid-β (Aβ) peptide into senile plaque, neurofibrillary tangles formed from hyperphosphorylated tau protein, and loss of cholinergic synapses in the cerebral cortex. The deposition of Aβ-loaded plaques results in microglial activation and subsequent production of reactive oxygen species (ROS), including free radicals. Neurons in aging and AD brains are particularly vulnerable to ROS and other toxic stimuli. Therefore, agents that decrease the vulnerability of neurons against ROS may provide therapeutic values for the treatment or prevention of AD. In the present study, our goal was to test whether intravenous immunoglobulin (IVIG) treatment could preserve as well as protect neurons from oxidative damage. We report that treatment with IVIG protects neuronal viability and synaptic proteins in primary rat hippocampal neurons. Further, we demonstrate the tolerability of IVIG treatment in the primary human fetal mixed brain cultures. Indeed, a high dose (20mg/ml) of IVIG treatment was well-tolerated by primary human brain cultures that exhibit a normal neuronal phenotype. We also observed a potent neuropreservatory effect of IVIG against ROS-mediated oxidative insults in these human fetal brain cultures. These results indicate that IVIG treatment has great potential to preserve and protect primary human neuronal-enriched cultures and to potentially rescue dying neurons from oxidative insults. Therefore, our findings suggest that IVIG treatment may represent an important therapeutic agent for clinical trials designed to prevent and delay the onset of neurodegeneration as well as AD pathology.

Cite this article as:

Lahiri K. Debomoy and Ray Balmiki, Intravenous Immunoglobulin Treatment Preserves and Protects Primary Rat Hippocampal Neurons and Primary Human Brain Cultures Against Oxidative Insults, Current Alzheimer Research 2014; 11 (7) . https://dx.doi.org/10.2174/1567205011666140812113851