Neuroprotectant FK506 inhibits glutamate‐induced apoptosis of astrocytes in vitro and in vivo

• DOI: 10.1111/j.1471-4159.2006.04136.x
• Publication Date: 2006-08-29T10:58:23Z
• Authors: Kinga Szydlowska; Malgorzata Zawadzka; Bozena Kaminska
• Keywords: Excitotoxicity

Neuron-astrocyte interactions are critical for signalling, energy metabolism, extracellular ion and glutamate homeostasis, volume regulation neuroprotection in the CNS. Glutamate uptake by astrocytes may prevent excitotoxic elevation determine neuronal survival. However, an excess of can cause death astrocytes. FK506, inhibitor calcineurin, immunosuppressive drug, is neuroprotective animal models neurologic diseases, including focal global ischaemia. In present work, we demonstrate that a single injection FK506 60 min after transient middle cerebral artery occlusion (MCAo) significantly decreases number terminal deoxynucleotidyl transferase nick-end labelling (TUNEL)-positive cells ischaemic cortex striatum. Using 3-D confocal microscopy found that, 24 h MCAo, many TUNEL-positive striatum Furthermore, exposure cultured cortical to 50-100 mM Glu induces apoptotic alterations nuclear morphology, DNA fragmentation, dissipation mitochondrial transmembrane potential (DeltaPsi) caspase activation. (1 muM) efficiently inhibits Glu-induced apoptosis astrocytes, fragmentation changes DeltaPsi. Our findings suggest modulation glutamate-induced astrocyte early reperfusion be novel mechanism FK506-mediated