Bragg D C, Boles J C, Meeker R B
Department of Neurology and Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Neurobiol Dis. 2002 Mar;9(2):173-86. doi: 10.1006/nbdi.2001.0459.
The choroid plexus contains a major reservoir of macrophages poised for efficient delivery of virus and neurotoxins to the brain after infection by lentiviruses such as human or feline immunodeficiency virus (FIV). However, their contribution to neurotoxicity is poorly understood. Medium from FIV-infected, choroid plexus macrophages applied to cultured feline cortical neurons induced a small acute calcium rise followed by either a delayed calcium deregulation (41%) or swelling and bursting (23%). NMDA glutamate receptor blockade prevented the acute calcium increase and antagonists to the IP(3) receptor, voltage-gated calcium channels and sodium channels suppressed both the acute and late increases. Analysis of intracellular calcium recovery in toxin-treated neurons after a brief exposure to glutamate, revealed a decrease in the rate and extent of recovery. The apparent diverse pharmacological contributions to intracellular calcium destabilization may be due to the ability of macrophage toxins to interfere with recovery of intracellular calcium homeostasis.
脉络丛含有大量巨噬细胞，在人类或猫免疫缺陷病毒（FIV）等慢病毒感染后，这些巨噬细胞随时准备将病毒和神经毒素高效递送至大脑。然而，它们对神经毒性的作用却鲜为人知。将来自感染FIV的脉络丛巨噬细胞的培养基应用于培养的猫皮质神经元，可诱导细胞内钙短暂急性升高，随后要么出现延迟性钙调节异常（41%），要么出现肿胀和破裂（23%）。NMDA谷氨酸受体阻断可防止急性钙升高，而IP(3)受体、电压门控钙通道和钠通道的拮抗剂则可抑制急性和晚期钙升高。对短暂暴露于谷氨酸的毒素处理神经元的细胞内钙恢复情况进行分析，结果显示恢复速率和程度均降低。对细胞内钙不稳定的明显不同药理学作用可能是由于巨噬细胞毒素干扰细胞内钙稳态恢复的能力所致。
