GDNF fails to inhibit LPS-mediated activation of mouse microglia.

GDNF is a potent neuroprotective factor for midbrain dopaminergic (mDA) neurons. In LPS-mediated models for mDA degeneration GDNF increases neuron survival and further reduces microglia activation. To elucidate the effects of GDNF on LPS-induced activation, primary microglia from C57BL/6 and NMRI mice have been analysed. In this study we demonstrate that GDNF is not able to inhibit LPS-mediated upregulation and release of the proinflammatory factors IL6 and TNFα. Moreover, we provide evidence that mouse microglia, in contrast to rat microglia, lack expression of the GDNF signalling receptor c-Ret resulting in abrogated activation of downstream signalling kinases Akt and Erk1/2.