We have now shown that ICI 182780 activation of microglia impacts neurons prenatally, with a delayed effect on their synaptic function. Deferred alteration of synaptic function depending on prenatal development has already been observed. For example, synaptic activity can be recorded on neurons from E18 rat hippocampus cultured for two weeks, whereas it is barely detected when neurons are cultured from E16 embryos. This indicates that prenatal differentiation of neurons is crucial for the later development of synaptic function. Epidemiological data have shown that infection during pregnancy increases the risk of schizophrenia and autism in adulthood. In humans, mutations of DAP12 induce the Nasu-Hakola disease, a presenile dementia that occurs in subjects in their 30��s. Adult mice knocked-out for DAP12 and adult mice born to inflamed mothers display behavioral or cognitive deficits reminiscent to some of the symptoms of autism and shizophrenia. Dementia are now mostly described as synaptopathies, and alterations of glutamatergic synapses have been involved in the etiology of autism. In addition, hypofunction of NMDAR has been implicated in the physiopathology of schizophrenia. Without excluding the involvement of secondary histological alterations, the data presented in this work provide a cellular basis for the neuropsychiatric defects induced by prenatal inflammation. Pattern recognition receptors recognize evolutionarily conserved LY2109761 molecular motifs on pathogens. PRRs are employed by the host immune system to evoke an immediate response to the invading pathogen through the production of inflammatory cytokines and chemokines. Because of the efficiency of this response, PRRs are attractive candidates as adjuvants for vaccines. PRRs span a broad range of receptors including Toll-like receptors, carbohydrate-binding calcium-dependent type lectin receptors, nucleotide binding oligomerization domain like receptors and intracellular viral receptors. The 11 human TLRs and 13 mouse TLRs are membranebound receptors which recognize pathogen-associated molecular patterns. TLRs can be either expressed on the cell surface or on endosomal vesicles. One particular TLR agonist undergoing clinical trials is synthetic cytosine phosphate guanine -containing oligodeoxynucleotides. CpG is taken up by cells in a clathrin-dependent manner and binds to TLR9 which is recruited from the endoplasmic reticulum to the endosome. This triggers the cytoplasmic Toll-IL-1R domain of TLR9 to bind to the adapter molecule, myeloid differentiation marker 88. MyD88 diverges into two signaling pathways, one mediated by NF-kB activation and one mediated through interferon regulatory factor 7 activation.