[P2–154]: DIFFERENTIAL SUSCEPTIBILITY OF STRIATAL, HIPPOCAMPAL AND CORTICAL NEURONS TO CASPASE‐6

• DOI: 10.1016/j.jalz.2017.06.805
• Publication Date: 2017-10-20T09:01:32Z
• Authors: Anastasia Noel; Benedicte Foveau; Andrea Claire LeB...
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Caspase-6 (Casp6), a cysteinyl protease of the caspase family, is activated early in Huntington disease (HD) and thought to contribute its pathogenesis by generating toxic fragment huntingtin (Htt). Active Casp6 TauΔCasp6 were assessed 50–70 yr old grade II HD age-matched control brains immunohistochemistry with neoepitope antisera against active Tau cleaved (TauΔCasp6). To assess whether activity induces HD-like pathogenesis, transgenic knock-in mouse (ACK) expressing self-activated form human medium spiny neurons indirect striatopallidal pathway, main brain circuit affected HD, was generated. Occasional intra-nuclear inclusions immunopositive for observed but not control, striatal neurons. Conversely, absent while neurofibrillary tangles frequent rare, hippocampus. Relative non-transgenic mice, protein increased 5.2, 2.5, 2.6 fold striatum, cortex hippocampus ACK brains, respectively. Detection Tubulin (TubΔCasp6) confirmed activity. littermate mice subjected psychiatric, motor, cognitive behavioral tests. No evidence depression evident forced swim sucrose consumption sensorimotor or locomotor deficits noticed nesting, clasping, rotarod, vertical pole, gait open field analyses. However, developed age-dependent episodic spatial memory identified novel object recognition test Barnes Morris water maze, Synaptic levels neuron numbers maintained cortex. Iba1 positive microglia phagocytic type 4 GFAP astroglial staining hippocampal stratum lacunosum molecular cortex, striatum. These data suggest that does induce motor inflammation, whereas impairs increases inflammation. results reveal specific vulnerability activation.