Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological condition

Biochemical Biomarkers and Neurodegenerative Diseases

In this book, we collected scientific articles, including reviews and research articles, showcasing the lastest literature on the importance of biochemical biomarkers in the management of neurodegenerative diseases, from screening to diagnosis, prognosis, and treatment

Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering with several neuroprogressive factors, and has been suggested to reverse neuropathological patterns seen in depression. These insights come at a time of great need for novel approaches, as prevalence is rising and current treatment options remain inadequate for a large number of people. The rapidly growing literature on ketamine’s antidepressant potential has yielded multiple proposed mechanisms of action, many of which have implications for recently elucidated aspects of depressive pathology. This review aims to provide the reader with an understanding of neuroprogressive aspects of depressive pathology and how ketamine is suggested to act on it. Literature was identified through PubMed and Google Scholar, and the reference lists of retrieved articles. When reviewing the evidence of depressive pathology, a picture emerges of four elements interacting with each other to facilitate progressive worsening, namely stress, inflammation, neurotoxicity and neurodegeneration. Ketamine acts on all of these levels of pathology, with rapid and potent reductions of depressive symptoms. Converging evidence suggests that ketamine works to increase stress resilience and reverse stress-induced dysfunction, modulate systemic inflammation and neuroinflammation, attenuate neurotoxic processes and glial dysfunction, and facilitate synaptogenesis rather than neurodegeneration. Still, much remains to be revealed about ketamine’s antidepressant mechanisms of action, and research is lacking on the durability of effect. The findings discussed herein calls for more longitudinal approaches when determining efficacy and its relation to neuroprogressive factors, and could provide relevant considerations for clinical implementation.publishedVersio

Astrocytic Abnormalities in Schizophrenia

Astrocytes are glial cells in the central nervous system (CNS), which contribute to CNS health and disease by participating in homeostatic, structural, and metabolic processes that play an essential role in facilitating synaptic transmission between neurons. Schizophrenia (SCZ) is a neuropsychiatric disorder associated with various positive and negative behaviors and interruption of executive function and cognition thought to be due partly to aberrations in signaling within neural networks. Recent research has demonstrated that astrocytes play a role in SCZ through various effects, including influencing immune system function, altering white matter, and mediating changes in neurotransmitters. Astrocytes are also known to play a role in inducing SCZ-associated changes in neuroplasticity, which includes alterations in synaptic strength and neurogenesis. Also, astrocyte abnormalities are linked to neurobehavioral impairments seen at the clinical level. The present chapter details general information on SCZ. It highlights the role of astrocytes in SCZ at molecular and behavioral levels, including neural changes seen in the disease, and the therapeutic implications of targeting astrocytes in SCZ

Underlying Mechanisms of Epilepsy

This book is a very provocative and interesting addition to the literature on Epilepsy. It offers a lot of appealing and stimulating work to offer food of thought to the readers from different disciplines. Around 5% of the total world population have seizures but only 0.9% is diagnosed with epilepsy, so it is very important to understand the differences between seizures and epilepsy, and also to identify the factors responsible for its etiology so as to have more effective therapeutic regime. In this book we have twenty chapters ranging from causes and underlying mechanisms to the treatment and side effects of epilepsy. This book contains a variety of chapters which will stimulate the readers to think about the complex interplay of epigenetics and epilepsy

Brain energy metabolism: A roadmap for future research

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2