The functions of the brain that allow us to think, feel, move, and perceive the world are the result of an exchange of information within a network composed of millions of specialized cells called neurons and glia. Neurons use neurotransmitters and other extracellular messengers to communicate with each other, and to constantly update and re-organize their network of connections in a process known as neural plasticity. In order to respond to these extracellular signals, neurons are equipped with specialized receptors that can recognize a single neurotransmitter a bit like a lock would recognize a key. They do this by activating or inhibiting a class of specialized signaling proteins and second messengers. Typically, signaling proteins are themselves organized in networks or pathways in which they activate or inhibit each other in order to integrate the mass of information received by a single cell and to regulate the biological functions of this cell. As we can see, rather than simply being a network of neurons, the brain can be seen as a sort of “Russian doll” in which each neuron is at the same time a part of networks with other neurons and the receptacle of many networks composed of signaling proteins. Two individual genes encode two paralogous signaling proteins: Glycogen Synthase Kinase -3 alpha and beta (GSK-3a, GSK-3b), named for its ability to phosphorylate a key metabolic enzyme of glycogen synthesis, glycogen synthase. This unique “glamour and gloom” protein kinase, has been intriguing many researches for over 30 years by its unusual features, still unknown mechanisms of its activation, its regulation by multiple “key” intracellular pathways, and its capacity to influence the functions of many substrates. Since GSK-3 was discovered, there has been significant progress in elucidating its regulatory roles in the neuron and the structure and functions of the brain. Lithium has been used as a gold standard in the treatment of bipolar disorder for 60 years; and “GSK-3’s renaissance” in psychiatry began with the discovery of GSK-3 as lithium's intracellular target. Since then, GSK3 has been implicated in the pathogenesis of mood disorders, schizophrenia, Alzheimer’s disease, ADHD, multiple sclerosis, Fragile X syndrome and Huntington disease. Connections to these and other diseases has led over the last 10 years to the generation of multiple types of GSK-3 inhibitors as promising therapeutic treatments for the aforementioned pathological conditions. During last couple years new genetic models have been generated, including conventional and conditional mouse models, allowing the discovery of new roles of GSK-3 in the mechanism of neurotransmitter action, neurodevelopment, learning and memory formation, GSK-3’s gene - effect on mouse behavior, and other functions. Thus, GSK-3 has been well-established as an intracellular second messenger for several neurotransmitter systems, and as an important therapeutic target of mood stabilizers, antipsychotics and psychomimetic drugs. The proposed Specific Topic for Frontiers in Neuroscience will be focused on the latest advances from leading laboratories in this area, subdivided into 5 topics: (1) GSK-3 history, mechanism of regulation, substrate specificity and comparison between the brain function of two GSK-3 genes through new animal models and cell biology approaches; (2) role of GSK-3 in neurodevelopment and neuronal structure; (3) involvement of GSK-3 in synaptic functions, learning and memory, and in serotonin and dopamine pathways; (4) role of GSK-3 in neuroinflammation, and application to the pathogenesis of multiple sclerosis, AD, schizophrenia, Fragile X, brain tumors, stroke and bipolar disorder; (5) development of GSK-3 inhibitors and their application in psychiatry, including special discussion about the mechanism of lithium action.

Homeostatic Control of Brain Function offers a broad view of brain health and diverse perspectives for potential treatments, targeting key areas such as mitochondria, the immune system, epigenetic changes, and regulatory molecules such as ions, neuropeptides, and neuromodulators. Loss of homeostasis becomes expressed as a diverse array of neurological disorders. Each disorder has multiple comorbidities - with some crossing over several conditions - and often disease-specific treatments remain elusive. When current pharmacological therapies result in ineffective and inadequate outcomes, therapies to restore and maintain homeostatic functions can help improve brain health, no matter the diagnosis. Employing homeostatic therapies may lead to future cures or treatments that address multiple comorbidities. In an age where brain diseases such as Alzheimer's or Parkinson's are ever present, the incorporation of homeostatic techniques could successfully promote better overall brain health. Key Features include · A focus on the homeostatic controls that significantly depend on the way one lives, eats, and drinks. · Highlights from emerging research in non-pharmaceutical therapies including botanical medications, meditation, diet, and exercise. · Incorporation of homeostatic therapies into existing basic and clinical research paradigms. · Extensive scientific basic and clinical research ranging from molecules to disorders. · Emerging practical information for improving homeostasis. · Examples of homeostatic therapies in preventing and delaying dysfunction. Both editors, Detlev Boison and Susan Masino, bring their unique expertise in homeostatic research to the overall scope of this work. This book is accessible to all with an interest in brain health; scientist, clinician, student, and lay reader alike.

More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. This book attempts to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. It explores insulin action at the most basic levels, through complex systems.