Upregulation of astrocytic and microglial markers precedes late onset neurodegenerative changes in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis (platform presentation)

Up regulation of astrocytic and microglial markers precedes late onset neuro-degenerative changes in the Cln3–/– mouse model of juvenile neuronal ceroid lipofuscinosis Introduction: Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder,with widespread regional atrophy and significant loss of GABAergic interneurones in the hippocampus and cortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether these events precede or are triggered by neuronal loss. Material and methods: Detailed morphological characterization and quantitative image analysis of the CLN3 null mutant (Cln3–/–) mouse model of juvenile NCL (JNCL). Results: Detailed morphological characterization revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread significant loss of hippocampal interneurones that was evident at 14 months of age. Quantitative image analysis demonstrated an early up-regulation of markers of astrocytic and microglial activation in presymptomatic Cln3–/– mice at 5 months of age. These events take place several months before significant neuropathological changes occur, but are transient in nature and are less prominent at 14 months of age. Conclusion: These data provide evidence for glial responses early in JNCL pathogenesis, but it will be important to determine the relative significance of these events during disease progression