Differences in TNF‑α and TNF‑R1 expression in damaged neurons and activated astrocytes of the hippocampal CA1 region between young and adult gerbils following transient forebrain ischemia.

Abstract

Tumor necrosis factor (TNF)-α and TNF receptor 1 (TNF-R1) play diverse roles in modulating the neuronal damage induced by cerebral ischemia. The present study compared the time-dependent changes of TNF-α and TNF-R1 protein expression levels in the hippocampal subfield cornu ammonis 1 (CA1) between adult and young gerbils following transient forebrain ischemia (tFI), via western blot and immunohistochemistry analyses. In adult gerbils, delayed neuronal death of pyramidal neurons, the principal neurons in CA1, was recorded 4 days after tFI; however, in young gerbils, delayed neuronal death was recorded 7 days after tFI. TNF-α protein expression levels gradually increased in both groups following tFI; however, TNF-α expression was higher in young gerbils compared with adult gerbils. TNF-R1 protein expression levels markedly increased in both groups 1 day after tFI. Subsequently, TNF-R1 expression gradually decreased in young gerbils, whereas TNF-R1 expression levels were irregularly altered in adult gerbils following tFI. Notably, TNF-α immunoreactivity significantly increased in pyramidal neurons in both groups 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF-α immunoreactivity was rarely exhibited in pyramidal neurons 4 days after tFI due to neuronal death, suggesting that TNF-α immunoreactivity was newly expressed in astrocytes. In young gerbils, TNF-α immunoreactivity increased in pyramidal neurons 4 days after tFI, and TNF-α immunoreactivity was newly expressed in astrocytes. In addition, TNF-R1 immunoreactivity was exhibited in pyramidal cells of both sham groups, and significantly increased 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF-R1 immunoreactivity was rarely exhibited 4 days after tFI, and astrocytes newly expressed TNF-R1 immunoreactivity. In young gerbils, TNF-R1 immunoreactivity increased in pyramidal neurons 4 days after tFI; however, TNF-R1 immunoreactivity was not reported in pyramidal neurons and astrocytes thereafter. Taken together, the results of the present study suggest that different expression levels of TNF-α and TNF-R1 in ischemic CA1 between adult and young gerbils may be due to age-dependent differences of tFI-induced neuronal death.