A Survey Assessment of Neurosurgeons' Interest in Osteopathic Medicine and Its Integration Into Their Practice.

Introduction: Osteopathic manipulative medicine (OMM) encompasses techniques guided by the tenets of osteopathy aimed at facilitating the body's natural self-healing capabilities as a treatment option for injury or illness. This approach recognizes the interrelationship of structure and function in promoting overall health. The clinical applications of OMM have been highly researched throughout different subspecialties of medicine; however, there is a notable lack of osteopathic-based research targeted toward neurosurgical patient populations.

Genetic ablation of neuronal mitochondrial calcium uptake halts Alzheimer's disease progression.

Alzheimer's disease (AD) is characterized by the extracellular deposition of amyloid beta, intracellular neurofibrillary tangles, synaptic dysfunction, and neuronal cell death. These phenotypes correlate with and are linked to elevated neuronal intracellular calcium ( Ca ) levels. Recently, our group reported that mitochondrial calcium ( Ca ) overload, due to loss of Ca efflux capacity, contributes to AD development and progression.

MICU1 regulates mitochondrial cristae structure and function independently of the mitochondrial Ca uniporter channel.

MICU1 is a calcium (Ca)-binding protein that regulates the mitochondrial Ca uniporter channel complex (mtCU) and mitochondrial Ca uptake. knockout mice display disorganized mitochondrial architecture, a phenotype that is distinct from that of mice with deficiencies in other mtCU subunits and, thus, is likely not explained by changes in mitochondrial matrix Ca content. Using proteomic and cellular imaging techniques, we found that MICU1 localized to the mitochondrial contact site and cristae organizing system (MICOS) and directly interacted with the MICOS components MIC60 and CHCHD2 independently of the mtCU.

Neuronal loss of NCLX-dependent mitochondrial calcium efflux mediates age-associated cognitive decline.

Mitochondrial calcium overload contributes to neurodegenerative disease development and progression. We recently reported that loss of the mitochondrial sodium/calcium exchanger (NCLX), the primary mechanism of Ca efflux, promotes Ca overload, metabolic derangement, redox stress, and cognitive decline in models of Alzheimer's disease (AD). However, whether disrupted Ca signaling contributes to neuronal pathology and cognitive decline independent of pre-existing amyloid or tau pathology remains unknown.

Enhanced NCLX-dependent mitochondrial Ca efflux attenuates pathological remodeling in heart failure.

Mitochondrial calcium (Ca) uptake couples changes in cardiomyocyte energetic demand to mitochondrial ATP production. However, excessive Ca uptake triggers permeability transition and necrosis. Despite these established roles during acute stress, the involvement of Ca signaling in cardiac adaptations to chronic stress remains poorly defined.

Molecular Signature of HFpEF: Systems Biology in a Cardiac-Centric Large Animal Model.

In this study the authors used systems biology to define progressive changes in metabolism and transcription in a large animal model of heart failure with preserved ejection fraction (HFpEF). Transcriptomic analysis of cardiac tissue, 1-month post-banding, revealed loss of electron transport chain components, and this was supported by changes in metabolism and mitochondrial function, altogether signifying alterations in oxidative metabolism. Established HFpEF, 4 months post-banding, resulted in changes in intermediary metabolism with normalized mitochondrial function.

Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation.

Fibroblast to myofibroblast differentiation is crucial for the initial healing response but excessive myofibroblast activation leads to pathological fibrosis. Therefore, it is imperative to understand the mechanisms underlying myofibroblast formation. Here we report that mitochondrial calcium (Ca) signaling is a regulatory mechanism in myofibroblast differentiation and fibrosis.

MCUB Regulates the Molecular Composition of the Mitochondrial Calcium Uniporter Channel to Limit Mitochondrial Calcium Overload During Stress.

Background: The mitochondrial calcium uniporter (mtCU) is an ≈700-kD multisubunit channel residing in the inner mitochondrial membrane required for mitochondrial Ca (Ca) uptake. Here, we detail the contribution of MCUB, a paralog of the pore-forming subunit MCU, in mtCU regulation and function and for the first time investigate the relevance of MCUB to cardiac physiology.

Methods: We created a stable knockout cell line () using CRISPR-Cas9n technology and generated a cardiac-specific, tamoxifen-inducible MCUB mutant mouse (CAG-CAT-MCUB x MCM; MCUB-Tg) for in vivo assessment of cardiac physiology and response to ischemia/reperfusion injury.

Impaired mitochondrial calcium efflux contributes to disease progression in models of Alzheimer's disease.

Impairments in neuronal intracellular calcium (Ca) handling may contribute to Alzheimer's disease (AD) development. Metabolic dysfunction and progressive neuronal loss are associated with AD progression, and mitochondrial calcium (Ca) signaling is a key regulator of both of these processes. Here, we report remodeling of the Ca exchange machinery in the prefrontal cortex of individuals with AD.