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. 2005 Mar 16;25(11):2952–2964. doi: 10.1523/JNEUROSCI.4456-04.2005

Figure 2.

Figure 2.

Stimulation of microglial mGlu2 induces a neurotoxic microglial phenotype. Cerebellar granule neurons were untreated (basal), incubated with MGCM from control unstimulated microglia (CONT), or exposed to MGCM from microglia exposed to different mGlu receptor agonists for 24 or 48 h, where indicated: t-ADA (250 μm) with or without the antagonist AIDA (250 μm), DCGIV (500 nm) with or without the antagonist MCCG (500 μm), NAAG (50 μm), and l-AP-4 (100 μm). Neuronal apoptosis was measured by Hoechst 33342 staining. A, A cerebellar granule neuron exposed to MGCM from t-ADA (group I)-treated microglia or DCGIV (group II)-treated microglia becomes apoptotic. MGCM from microglia treated with the group II mGlu3 agonist NAAG and the group III mGlu agonist l-AP-4 does not evoke CGC neuronal apoptosis. B, The neurotoxicity of MGCM from t-ADA-treated microglia is not reduced when the microglia are coexposed to the group I antagonist AIDA. The MGCM from DCGIV-treated microglia is significantly reduced when the microglia are coexposed to the group II antagonist MCCG. C, The direct addition of the mGlu receptor agonists to neuronal cultures in the presence of MGCM from control unstimulated microglia revealed that t-ADA is directly neurotoxic. D, The direct neurotoxicity of t-ADA can be abated by the addition of the group I antagonist AIDA to the neuronal cultures. E, Activation of microglial mGlu2 induces the release of soluble, stable neurotoxins. Untreated microglia in coculture with neurons (CONT) did not induce apoptosis above that in primary cultures of CGC neurons alone (basal). Neurons were added to the microglial cultures 24 h after the addition of the mGlu receptor agonist t-ADA, DCGIV, NAAG, or l-AP-4. In each case, the number of apoptotic neurons per field was counted in six separate fields on atleast four coverslips per condition and is expressed as a percentage of total cells (mean ± SEM). Significance values are shown compared with control MGCM-treated neuronal cultures in A-D and control cocultures (CONT; neurons cultured with microglia) in E, unless indicated otherwise (***p < 0.0005).