About this Research Topic
The maintenance of glucose homeostasis is vital for the metabolic demands of brain function. Impairment of energy metabolism is a hallmark of brain aging and it is particularly accentuated in neurodegenerative diseases. Clinically, age- and disease-related changes in brain metabolism are manifested as hypometabolism or a bioenergetic deficit that may precede inflammatory responses. This bioenergetic deficit –indicating the critical role of mitochondria– is associated with oxidative stress, i.e., a chronic formation of oxidants at variance with acute responses entailing NADPH oxidase activity. Hence, a growing body of evidence supports mitochondrial dysfunction and chronic oxidative stress as major contributors to synaptic abnormalities and the resulting cognitive decline inherent in brain aging and neurodegenerative diseases. Neuroinflammatory changes, entailing microglial activation and accompanied by up-regulation of inflammatory cytokines, are common to neurodegenerative diseases and, albeit less dramatic, these neuroinflammatory changes also occur with age; although a precise molecular mechanism remains unknown, there are correlational data indicating the importance of microglial activation in inducing age-related deficits in synaptic function and the associated cognitive decline. Oxidative stress is also associated with neuroinflammatory responses. Several groups advocate for a causal consequence between mitochondrial dysfunction, propagation of neuronal dysfunction, and neurodegeneration; others support the strong influence of microglia activation, neuroinflammation, and oxidative stress that lead to synaptic transmission and behavioral changes. Certainly, inflammatory responses exacerbate mitochondrial dysfunction and vice versa but it seems that these mechanistic diversities have cellular redox dysregulation as a common denominator. A sequential view of the mechanisms inherent in brain aging and progression of neurodegeneration is being replaced by the understanding that several mechanisms co-exist and interact with each other. The significance of the systemic environment in each of the processes associated with brain aging and progression of neurodegenerative diseases such as Alzheimer’s disease should be recognized in light of observations that insulin resistance and systemic inflammation affect synaptic transmission in aging and disease brains.
This research topic focuses on the bioenergetic deficits and activation of inflammatory responses, their redox (oxidative stress) regulation, and their role in synaptic plasticity and cognition in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems will be reviewed in terms of their causative or in-tandem occurrence and how does the systemic environment, e.g., insulin resistance, diabetes, and inflammation, impact on brain function. This call for papers also aims to create a unique forum for in-depth discussions on cellular mechanisms and their forward translation into interventions to prevent, delay, or treat the memory loss and cognitive slowing associated with brain aging and neurodegeneration, as well as the reverse translation from the progression of clinical studies (e.g., non-invasive neuroimaging techniques) to the basic discovery research.
This research topic focuses on the bioenergetic deficits and activation of inflammatory responses, their redox (oxidative stress) regulation, and their role in synaptic plasticity and cognition in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems will be reviewed in terms of their causative or in-tandem occurrence and how does the systemic environment, e.g., insulin resistance, diabetes, and inflammation, impact on brain function. This call for papers also aims to create a unique forum for in-depth discussions on cellular mechanisms and their forward translation into interventions to prevent, delay, or treat the memory loss and cognitive slowing associated with brain aging and neurodegeneration, as well as the reverse translation from the progression of clinical studies (e.g., non-invasive neuroimaging techniques) to the basic discovery research.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
