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Endogenous adenosine protects CA1 neurons from kainic acid-induced neuronal cell loss in the rat hippocampus


: Dr Yasuji Matsuoka, as above.


CA3 pyramidal neurons in the rat hippocampus show selective vulnerability to the intracerebroventricular injection of kainic acid (KA). However, the mechanism of this selective neuronal vulnerability remains unclear. In this study, we examined the contribution of endogenous adenosine, a potent inhibitory neuromodulator, to the differences in the neuronal vulnerability of the hippocampus, using microtubule-associated protein (MAP)-2, phosphorylated c-Jun, and major histocompatibility complex (MHC) class II immunoreactivities as markers for neuronal cell loss, neuronal apoptosis and glial activation, respectively. Pretreatment with 8-cyclopenthyltheophylline (CPT), an A1 adenosine receptor antagonist, significantly exacerbated KA-induced neuronal cell loss in both the CA1 and CA3. Although c-Jun phosphorylation, a critical step in neuronal apoptosis, was not detected in the vehicle-injected rat hippocampus, c-Jun phosphorylation was induced in the CA3 by the injection of KA alone. Pretreatment with CPT induced c-Jun phosphorylation in both the CA1 and CA3. MHC class II antigen was also detected in the regions of c-Jun phosphorylation. Coadministration of N6-cyclopenthyladenosine (CHA), an A1 adenosine receptor agonist, attenuated the neuronal cell loss in the CA1 and CA3 with or without pretreatment with CPT. These results strongly suggest that endogenous adenosine has neuroprotective effects against excitotoxin-induced neurodegeneration in the CA1 through its A1 receptors.