000 nam a22 4500
001 14393
100 _a20220601d2022 u||y0pory50 ba
101 _aeng
102 _aPT
200 _aInvestigating the role of innate imune memory in microglial-mediated synaptic remodeling
_fFrancisco Mendes Lopes
_gorient. Dorothy P. Schafer, Rita Oliveira Teodoro
210 _aLisboa
_cNOVA Medical School
_d2022
215 _a53 p.
330 _aInnate immune memory is the process by which the immune response led the innate immune system is enhanced or dampened according to previous inflammatory challenges. Recently, microglia, the tissue-resident macrophages of the brain, were found to display immune training and tolerance, two key elements of innate immune memory, characterized by epigenetic molecular mechanisms which lead to sustained transcriptional changes. Considering microglia’s active role in regulating neural circuits in adulthood and disease, by engulfing and removing synaptic connections, this thesis aims to assess the hypothesis that immune memory shapes microglia-mediated synapse remodeling. I took advantage of the barrel cortex system, where microglia have been shown to engulf excitatory synapses following unilateral whisker cauterization in neonatal mice, leading to synapse loss. In adult mice, I further show that sensory lesioning elicited microglia to engulf thalamocortical inputs in the deprived barrels. However, this assay required me to establish a new immunostaining protocol that eliminates microglial autofluorescence from the synaptic engulfment analysis, allowing proper quantification. Strikingly, after optimizing this protocol, I found that microglia no longer engulfed synapses in adult mice that had received a single injection of lipopolysaccharide one month before lesioning. On the other hand, microglia from mice that received four consecutive injections displayed a higher baseline of engulfment in both the control and deprived hemispheres. These results demonstrate that immune memory alters microglia-mediated synapse remodeling prior to and in response to lesioning.
606 _aImmune System
606 _aImmunologic Memory
606 _aImmune Training and Tolerance
606 _aMicroglia
606 _aAcademic Dissertation
606 _aPortugal
610 _aUniversidade NOVA de Lisboa
610 _aNOVA Medical School
610 _aDissertação de Mestrado
610 _aInvestigação Biomédica
610 _a2022
700 _aLopes
_bFrancisco Mendes
702 _4727
_922400
_aSchaffer
_bDorothy P.
702 _4727
_922381
_aTeodoro
_bRita
801 _aPT
_bNMS
_gRPC
856 _uhttp://hdl.handle.net/10362/139151
090 _a14393
942 _cDLEC
_n0