Preconditioning with lipopolysaccharide activates spinal cord microglia without causing neuropathology

Biological Sciences: 3rd Place (The Ohio State University Denman Undergraduate Research Forum)Microglia, the resident immune cells of the central nervous system (CNS), normally provide sentinel functions in intact CNS but once activated by injury or disease, microglia can exacerbate CNS pathology. However, not all forms of microglia activation are injurious. Injecting sub-lethal doses of lipopolysaccharide (LPS), activates microglia but without causing damage. This “preconditioning” can be neuroprotective in the brain; however, it is not known if spinal cord microglia also can be preconditioned with LPS. To test whether LPS can condition spinal cord microglia, mice were injected intraperitoneally daily for four consecutive days with LPS (1mg/kg). The next day, spinal cords were processed and microglia morphology and phenotype were documented using light and fluorescent microscopy. LPS caused visible changes in microglia morphology throughout spinal cord white and gray matter, with microglia occupying more than 2x the surface area in gray matter compared with white matter as compared with comparable measures in saline-injected mice. These effects were most evident in cervical spinal cord as compared with thoracic and lumbar spinal levels. Inflammatory markers including CD16/32, inducible nitric oxide synthase (iNOS) and galectin-3 were increased in LPS-activated microglia but without obvious neuron pathology or cell-death. Activated microglia were often associated with blood vessels suggesting that i.p. LPS might activate microglia across the blood-spinal cord barrier. Ependymal cells lining the central canal also appeared to be proliferating in mice injected with LPS. This response might be harnessed for CNS repair. Indeed, ependyma have stem-like properties and can support axon growth. While LPS usually activates immune cells to be inflammatory and detrimental to surrounding tissues, the current data indicate that preconditioning can prime microglia without eliciting injurious effector functions. By understanding how LPS preconditioning affects microglial phenotype and function, new therapies might be developed to treat CNS trauma and disease.Academic Major: Neuroscienc

Preconditioning with lipopolysaccharide activates spinal cord microglia without causing neuropathology

Microglia, the resident immune cells of the central nervous system (CNS), normally provide sentinel functions in intact CNS but once activated by injury or disease, microglia can exacerbate CNS pathology. However, not all forms of microglia activation are injurious. Injecting sub-lethal doses of lipopolysaccharide (LPS), activates microglia but without causing damage. This “preconditioning” can be neuroprotective in the brain; however, it is not known if spinal cord microglia also can be preconditioned with LPS. To test whether LPS can condition spinal cord microglia, mice were injected intraperitoneally daily for four consecutive days with LPS (1mg/kg). The next day, spinal cords were processed and microglia morphology and phenotype were documented using light and fluorescent microscopy. LPS caused visible changes in microglia morphology throughout spinal cord white and gray matter, with microglia occupying more than 2x the surface area in gray matter compared with white matter as compared with comparable measures in saline-injected mice. These effects were most evident in cervical spinal cord as compared with thoracic and lumbar spinal levels. Inflammatory markers including CD16/32 and inducible nitric oxide synthase (iNOS) were increased in LPS-activated microglia but without obvious neuron pathology or cell-death. Activated microglia were often associated with blood vessels suggesting that i.p. LPS might activate microglia across the blood-spinal cord barrier. Ependymal cells lining the central canal also appeared to be proliferating in mice injected with LPS. This response might be harnessed for CNS repair. Indeed, ependyma have stem-like properties and can support axon growth. While LPS usually activates immune cells to be inflammatory and detrimental to surrounding tissues, the current data indicate that preconditioning can prime microglia without eliciting injurious effector functions. By understanding how LPS preconditioning affects microglial phenotype and function, new therapies might be developed to treat CNS trauma and disease.No embargoAcademic Major: Neuroscienc

Mapping Synaptic Pathology within Cerebral Cortical Circuits in Subjects with Schizophrenia

Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g., dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin), or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article we consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, we provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex

Rhode Island College Letter

Letter to accompany the honorary degree from Rhode Island College presented to Madeleine Giguère by David E. Sweet, President of Rhode Island College.https://digitalcommons.usm.maine.edu/giguere-awards/1030/thumbnail.jp

Introduction

Introduction to Symposiu