Onemorestep Posted April 27, 2022 Report Share Posted April 27, 2022 https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-014-0222-3 We found that activation of TLR4 by lipopolysaccharide (LPS) reduces GABAergic synaptic activities through both presynaptic and postsynaptic mechanisms. Specifically, LPS causes the release of IL-1β from microglia. IL-1β in turn suppresses GABA receptor activities at the postsynaptic site through activating protein kinase C (PKC) in neurons. GABA synthesis at the presynaptic site is reduced upon activation of TLR4. Glial glutamate transporter activities are suppressed by IL-1β and PKC activation induced by LPS. The suppression of glial glutamate transporter activities leads to a deficiency of glutamine supply, which results in an attenuation of the glutamate-glutamine cycle-dependent GABA synthesis. These findings shed light on understanding synaptic plasticity induced by activation of TLR4 under neuroinflammation and identify GABA receptors, glial glutamate transporters, IL-1β and PKC as therapeutic targets to abrogate abnormal neuronal activities following activation of TLR4 in pathological pain conditions. —— question: how does inhibiting microglia effect glutamate-glutamine cycle-dependent GABA synthesis? It seems to be negative but overactivation of microglia damages glutamate neurons and nearby neurons. Hmm Link to comment Share on other sites More sharing options...
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