Regulation and roles of mitophagy at synapses

Publication date: Available online 19 February 2020Source: Mechanisms of Ageing and DevelopmentAuthor(s): Konstantinos Palikaras, Nektarios TavernarakisAbstractMaintenance of synaptic homeostasis is a challenging task, due to the intricate spatial organization and intense activity of synapses. Typically, synapses are located far away from the neuronal cell body, where they orchestrate neuronal signalling and communication, through neurotransmitter release. Stationary mitochondria provide energy required for synaptic vesicle cycling, and preserve ionic balance by buffering intercellular calcium at synapses. Thus, synaptic homeostasis is critically dependent on proper mitochondrial function. Indeed, defective mitochondrial metabolism is a common feature of several neurodegenerative and psychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), bipolar disorders and schizophrenia among others, which are also accompanied by excessive synaptic abnormalities. Specialized and compartmentalized quality control mechanisms have evolved to restore and maintain synaptic energy metabolism. Here, we survey recent advances towards the elucidation of the pivotal role of mitochondria in neurotransmission and implicating mitophagy in the maintenance of synaptic homeostasis during ageing.
Source: Mechanisms of Ageing and Development - Category: Geriatrics Source Type: research

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Authors: Morris G, Maes M, Berk M, Carvalho AF, Puri BK Abstract Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson's disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurode...
Source: Journal of the Association of European Psychiatrists - Category: Psychiatry Tags: Eur Psychiatry Source Type: research
We describe the first human single-nuclei transcriptomic atlas for substantia nigra (SN), generated by sequencing ~ 17,000 nuclei from matched cortical and SN samples.   We show that common genetic risk for Parkinson’s disease (PD) is associated with dopaminergic neuron (DaN)-specific gene expression including mitochondrial functioning, protein folding and ubiquitination pathways. We also identified a distinct cell-type association between PD risk and oligodend rocyte-specific expression implicating metabolic and gene expression regulation networks. Beyond PD, we find SN DaNs and GABAergic neurons to be associat...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Publication date: Available online 23 December 2019Source: Pharmacological ResearchAuthor(s): Megan Beauchemin, Ramaz Geguchadze, Anyonya R. Guntur, Kathleen Nevola, Phuong T. Le, Deborah Barlow, Megan Rue, Calvin P.H. Vary, Christine W. Lary, Katherine J. Motyl, Karen L. HouseknechtAbstractAtypical antipsychotic (AA) medications including risperidone (RIS) and olanzapine (OLAN) are FDA approved for the treatment of psychiatric disorders including schizophrenia, bipolar disorder and depression. Clinical side effects of AA medications include obesity, insulin resistance, dyslipidemia, hypertension and increased cardiovascul...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 20 September 2019Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Gerwyn Morris, Basant K. Puri, Adam J. Walker, Michael Maes, Andre F. Carvalho, Ken Walder, Michael BerkAbstractActivated immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways and consequent mitochondrial aberrations are involved in the pathophysiology of psychiatric disorders including major depression, bipolar disorder and schizophrenia. They offer independent and shared contributions to pathways underpinning medical comorbidities including insulin resistance, metabolic syndrome, obesity and card...
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research
Globally, psychiatric disorders, such as anxiety disorder, bipolar disorder, schizophrenia, depression, autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD) are becoming more prevalent. Although the exact pathological alterations are not yet clear, recent studies have demonstrated that widespread changes of very complex metabolic pathways may partially underlie the pathophysiology of many psychiatric diseases. Thus, more attention should be directed to metabolic-based therapeutic interventions in the treatment of psychiatric disorders. Emerging evidence from numerous studies suggests that administra...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Albert Sanfeliu1, Karsten Hokamp2, Michael Gill1 and Daniela Tropea1,3*1Neuropsychiatric Genetics, Department of Psychiatry, School of Medicine, Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland2Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland3Department of Psychiatry, School of Medicine, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, IrelandRett syndrome is a rare neuropsychiatric disorder with a wide symptomatology including impaired communication and movement, cardio-respiratory abno...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion Taken together, evidence from animal and human studies demonstrates that the brain detects levels of circulating nutrients and hormones and consequently organizes an outward response that contributes to the regulation of whole-body glucose homeostasis. However, there are major knowledge gaps about the exact nature of this response and its relative importance compared to peripheral processes. As we have seen, animal studies have provided an anatomical map of CNS glucose regulation and have identified important neurons and neural circuits involved. Additionally, the CNS sensing of key nutrients and hormones has b...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies and compartmentalization. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex and hippocampus are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known t...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
This study shows that some genetic changes linked to cancer are present in surprisingly large numbers of normal cells. We still have a long way to go to fully understand the implications of these new findings, but as cancer researchers, we can't underestimate the importance of studying healthy tissue." Early Onset of Menopause Correlates with Shorter Life Expectancy https://www.fightaging.org/archives/2018/10/early-onset-of-menopause-correlates-with-shorter-life-expectancy/ Aging is a phenomenon affecting all organs and systems throughout the body, driven by rising levels of molecular damage. The v...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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