Neuroscience
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Peripheral neuropathy is one of the main complications of diabetes. The pathogenesis of this affectation is not completely understood. Several studies refer to hyperglycemia as the principal cause of diabetic neuropathy. ⋯ Treatment with metformin for 4 weeks reversed some of the fructose-induced changes in protein expression. Taken together, these data suggest that insulin resistance induced by fructose reproduces several aspects of neuropathic-like pain. Our data also suggest that nociceptive hypersensitivity in this model is due to the modulation of several ionic channels at the primary afferent neurons.
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Huntington's disease (HD) is a genetic neurodegenerative disorder of the central nervous system characterized by choreatic movements, behavioral and psychiatric disturbances and cognitive impairments. Deficits in learning and memory are often the first signs of disease onset in both HD patients and mouse models of HD and are in part regulated by the hippocampus. In the R6/2 mouse model of HD, GABAergic transmission can be excitatory in the hippocampus and restoring inhibition can rescue the associated memory deficits. ⋯ Symptomatic mice also exhibited a change in the probability of GABA release and changes in the basic membrane properties including neuronal excitability and input resistance. These electrophysiological changes in presymptomatic and symptomatic R6/2 mice were further accompanied by alterations in the protein expression level of pre- and postsynaptic inhibitory markers. Taken together, the present findings demonstrate profound alterations in the inhibitory neurotransmission in the hippocampus across the lifespan of the disease, including prior to neuronal degeneration, which suggests that the inhibitory hippocampal synapses may prove useful as a target for future therapeutic design.
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Major depressive disorder (MDD) is a very common disease that affects more than 350 million people worldwide, representing an enormous socioeconomic burden. From a clinical perspective, MDD can be divided into different subtypes, such as melancholic or atypical MDD. Interestingly, increasing evidence points toward an involvement of the immune system in MDD pathogenesis. ⋯ Next, we examine the regional specificity of neuroinflammation, which shows striking overlaps with neural patterns activated in atypical MDD. Furthermore, we outline how inflammation may translate to subtype-specific clinical features and we suggest how this could be used for diagnostic and treatment purposes. By providing a link back to a dysregulated immune system as a contributing factor to MDD subtypes, we explain how brain regions particularly affected by certain subtypes may regulate the cortisol circuitry.
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Positron emission tomography (PET) provides spatially localized information about brain metabolism and function and innovative tracers have extended this potential to the study of neuroinflammation (NI), an important process in the pathophysiology of several neurological disorders. However, PET is limited by low spatial resolution. Conversely, Magnetic Resonance Imaging (MRI) affords high-resolution information about brain anatomy and metabolism which can complement PET-related information as well as aid in post-processing of PET data. ⋯ While, the clinical applicability and impact on diagnostic accuracy of PET/MRI in neurological disorders is still under investigation, the study of NI, a complex processes mediated by multiple metabolic pathways and hence likely characterized by different biomarkers, represents an opportunity to characterize the added value of joint MRI-PET techniques in a clinical context. This would in turn offer improved diagnostic and prognostic tools in several neurological disorders in which NI is a key mediator. This review aims at summarizing the current state as well as future potential of using hybrid PET/MRI for characterizing NI phenomena, both in terms of technical challenges and clinical relevance.
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The gut-brain axis communicates the brain with the gut microbiota, a bidirectional conduit that has received increasing attention in recent years thanks to its emerging role in brain development and function. Alterations in microbiota composition have been associated to neurological and psychiatric disorders, and several studies suggest that the immune system plays a fundamental role in the gut-brain interaction. ⋯ In this "Perspective" article, we discuss recent efforts to combine data on the gut microbiota with the features that can be obtained from the conversion of brain images into mineable data. The subsequent analysis of these data for diagnostic and prognostic purposes is an approach we call radiomicrobiomics and it holds tremendous potential to enhance our understanding of this fascinating connection.