Question:
Which type of TNF receptors and which cells are the cause for diminished amplitudes of CSD by TNFα in the adult rat?
Methods:
In spontaneously breathing anesthetized adult rats (sodium thiopentone, 100 mg/kg, i.p.) KCl-induced CSD were recorded in cerebral cortex with two pairs of micropipettes at layer V. A cortical area was pretreated (1 hour) either with a TNF receptor 1 (TNFR1) antibody, or with a TNF receptor 2 (TNFR2) antibody, or with the GABAA receptor antagonist bicuculline. We tested for CSD prior and after pretreatment, and during the subsequent application of 5 ng TNFα for two hours. Effects of TNFα on CSD were also studied in wild type mice and in mice with genetically knocked out TNFR1 or TNFR2. After sacrificing the rats, the localization of TNFR1 and TNFR2 was assessed immunohistologically.
Results:
Blockade of the TNFR1 did not change the effect of TNFα on CSD (amplitude 38.2 ± 10.0% of controls, n = 6). The blockade of the TNFR2 significantly attenuated the reduction of CSD amplitudes by TNFα (amplitude 81.3 ± 5.4% of controls, n = 5). TNFα diminished CSD amplitudes in wild type mice, and in TNFR1 k.o. mice, but only slightly in TNFR2 k.o. mice (control 16.3 ± 3.7mV, after TNFα 10.0 ± 1.0mV, n = 3 each). The GABAA receptor antagonist bicuculline prevented the diminishing effects of TNFα on CSD amplitudes (73.6 ± 17.2% of controls, n = 6). Immunohistochemistry showed the expression of the TNFR2 but not of TNFR1 on neurons and interneurons, but not on glial membranes.
Conclusions:
The results indicate that TNFα might decrease CSD via activation of interneurons that express the TNFR2.
