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1. UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis

Author

Jiandong Sun, Guoqi Zhu, Yan Liu, Steve Standley, Angela Ji, Rashmi Tunuguntla, Yubin Wang, Chad Claus, Yun Luo, Michel Baudry, and Xiaoning Bi

Subjects
Biology (General), QH301-705.5
Abstract

Gated solely by activity-induced changes in intracellular calcium, small-conductance potassium channels (SKs) are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics, and Ca2+ sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and overexpression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function.

Published
2015
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3. Multilevel Stabilization Screws Prevent Proximal Junctional Failure and Kyphosis in Adult Spinal Deformity Surgery: A Comparative Cohort Study

Author

Ascher, Kaufmann, Chad, Claus, Doris, Tong, Connor, Hanson, Daniel, Carr, Clifford, Houseman, and Teck-Mun, Soo

Subjects
Adult, Cohort Studies, Bone Screws, Skin Abnormalities, Humans, Microphthalmos, Genetic Diseases, X-Linked, Surgery, Kyphosis, Longitudinal Studies, Neurology (clinical), Spine, Musculoskeletal Abnormalities
Abstract

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) occurred in up to 40% of patients with adult spinal deformity (ASD) who underwent open thoracolumbar fusion. Proximal stabilization techniques have been investigated to prevent PJK/PJF without conclusive results.To demonstrate reductions in PJK/PJF with multilevel stabilization screws (MLSSs).This observational longitudinal cohort study compares MLSSs with standard instrumentation. We reviewed the charts of consecutive patients with ASD undergoing open thoracolumbar fusion (3 levels, extending cranially above T6 and caudally below L1) from 2009 to 2017 and were followed for2 yr postoperatively. We defined PJF using the International Spine Study Group criteria and PJK as a Cobb angle increase10°. We defined the upper instrumented vertebra as the most cephalad vertebral body with bilateral MLSSs. Confounders, MLSS-specific complications, and radiographic outcomes were collected. We evaluated comparability between groups using univariate analyses. We adjusted for covariates by using multivariable regressions modeling PJF and PJK separately with a P-value.00625 considered significant after the Bonferroni correction. Sensitivity analysis accounted for those lost to follow-up.Seventy-six patients (50 MLSS vs 26 controls) were included. MLSS patients were significantly older (64.5 ± 8.9 vs 54.8 ± 19.9 yr, P = .024) and had significantly lower PJF incidence (10.0% vs 30.8%, P = .023) and less kyphosis (1.3° ± 5.3° vs 5.2° ± 6.3°, P = .014). Multivariable analysis demonstrated a significant independent association between MLSSs and decreased odds of PJF (odds ratio: 0.11, 0.02-0.53, P = .006). Perioperative complications did not significantly differ between cohorts.MLSSs are safe and efficacious in reducing PJF/PJK in patients with ASD undergoing open thoracolumbar fusion.

Published
2022

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