GDNF fails to inhibit LPS-mediated activation of mouse microglia

• C57BL/6- and NMRI-derived primary mouse microglia were analysed.
• GDNF does not inhibit LPS-induced microglia activation.
• Mouse microglia express Gfra1 and to low Ncam levels, but lack c-Ret expression.
• GDNF fails to trigger activation of Akt and Erk1/2 in 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.