A role for astrocyte‐derived amyloid β peptides in the degeneration of neurons in an animal model of temporal lobe epilepsy

摘要: Kainic acid, an analogue of the excitatory neurotransmitter glutamate, can trigger seizures and neurotoxicity in hippocampus other limbic structures a manner that mirrors neuropathology human temporal lobe epilepsy (TLE). However, underlying mechanisms associated with remain unclear. Since amyloid-β (Aβ) peptides, which are critical development Alzheimer's disease, mediate toxicity by activating glutamatergic NMDA receptors, it is likely enhanced transmission renders hippocampal neurons vulnerable to kainic acid treatment may involve Aβ peptides. Thus, we seek establish what role plays acid-induced using vivo vitro paradigms. Our results show systemic injection adult rats triggers seizures, gliosis loss neurons, along increased levels/processing amyloid precursor protein (APP), resulting production Aβ-related The changes APP were evident primarily activated astrocytes, implying for astrocytic toxicity. Accordingly, showed treating rat primary cultured astrocytes lead production/secretion without any compromise cell viability. Additionally, revealed reduces neuronal viability more neuronal/astrocyte co-cultures than pure culture, this attenuated precluding production. Collectively, these indicate peptides from contribute acid-treated rats. administration neuropathological resembling TLE, APP/Aβ derived have TLE pathogenesis.