Mitochondrial complex 1 activity measured by spectrophotometry is reduced across all brain regions in ageing and more specifically in neurodegeneration

Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70–71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions

How phenotype guides management of the most common malignant salivary neoplasms of the Larynx?

Salivary gland carcinomas of the larynx are uncommon. Adenoid cystic carcinoma is the most prevalent type of salivary gland carcinoma in this region, although other histologies such as mucoepidermoid carcinoma and adenocarcinomas have been reported. These tumors may present with advanced-stage due to nonspecific symptoms and their relatively slow-growing nature. The index of suspicion for a non-squamous cell carcinoma entity should be high when a submucosal mass is present. An accurate diagnosis is mandatory due to the impact each biologic entity has on treatment and outcome. Data concerning treatment and outcome are scarce, but primary surgery with utmost focus on free surgical margins is the treatment of choice. The role of adjuvant radiotherapy has not been well defined, although there is an agreement that it should be considered in advanced-stage or high-grade disease. This review considers only the most common malignant salivary neoplasms of the larynx with a focus on clinical management of these tumors

Surgery for Malignant Tumors of the Minor Salivary Glands.

none6noneLicitra L Locati L.D.; Lombardi D.; Accorona R.; Lancini D.; Rampinelli V.; Bozzola A.; Nicolai P.Lombardi, D.; Accorona, R.; Lancini, D.; Rampinelli, V.; Bozzola, A.; Nicolai, P

Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases.

Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium ( www.cebiond.org ), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.We acknowledge the support of the CeBioND EU Joint Programme for Neurodegenerative Disease Research (JPND; www.jpnd.eu). The programme is supported through the following national funding organisations: Canada, CIHR; Germany, BMBF; Ireland: Science Foundation Ireland (14/JPND/ B3077); Italy: MIUR; Sweden: VR