Intracellular Signaling Cascades in Bipolar Disorder
Bipolar spectrum disorders carry a significant public health burden. Disproportionately high rates of suicide, incarceration, and comorbid medical conditions necessitate an extraordinary focus on understanding the intricacies of this disease. Elucidating
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Contents 1 Introduction 2 Mitochondrial Dysfunction 3 Calcium Channel Modulators 4 Intracellular Signaling and Inflammation 5 Glycogen Synthase Kinase 3-Beta (GSK3β) 6 Protein Kinase C (PKC) and Diacylglycerol (DAG) 7 Neurotrophins 8 Glutamatergic System 9 Dopaminergic System 10 Neurohormonal System 11 Purinergic System and Mania 12 Conclusion References
Abstract Bipolar spectrum disorders carry a significant public health burden. Disproportionately high rates of suicide, incarceration, and comorbid medical conditions necessitate an extraordinary focus on understanding the intricacies of this disease. Elucidating granular, intracellular details seems to be a necessary preamble to advancing promising therapeutic opportunities. In this chapter, we review a wide range of intracellular mechanisms including mitochondrial energetics, calcium
G. H. Jones, C. Rong, and R. Machado-Vieira (*) Department of Psychiatry, University of Texas Health Science Center at Houston, Houston, TX, USA e-mail: [email protected] A. S. Shariq Department of Psychiatry, Texas Tech University Health Science Center, El Paso, TX, USA Texas Tech University Health Science Center, Paul L. Foster School of Medicine, El Paso, TX, USA A. Mishra Texas Tech University Health Science Center, Paul L. Foster School of Medicine, El Paso, TX, USA © Springer Nature Switzerland AG 2020 Curr Topics Behav Neurosci https://doi.org/10.1007/7854_2020_157
G. H. Jones et al.
signaling, neuroinflammation, the microbiome, neurotransmitter metabolism, glycogen synthase kinase 3-beta (GSK3β), protein kinase C (PKC) and diacylglycerol (DAG), and neurotrophins (especially BDNF), as well as the glutamatergic, dopaminergic, purinergic, and neurohormonal systems. Owing to the relative lack of understanding and effective therapeutic options compared to the rest of the spectrum, special attention is paid in the chapter to the latest developments in bipolar depression. Likewise, from a therapeutic standpoint, special attention should be paid to the pervasive mechanistic actions of lithium as a means of amalgamating numerous, disparate cascades into a digestible cognitive topology. Keywords Brain-derived neurotrophic factor (BDNF) · Glycogen synthase kinase 3-beta (GSK3β) · Lithium · Protein kinase C (PKC) and diacylglycerol (DAG)
1 Introduction BD has a lifetime prevalence of approximately 4% in the general population and imposes substantial medical and psychosocial morbidity on patients and families (Kessler et al. 2005). Bipolar disorder (BD) has been associated with a wide range of neurobiological models whose pathophysiological mechanisms have not yet been fully characterized. As our attempts to understand and treat this disease evolve, the clearer it becomes that BD is a multifactorial disease comprised of many dynamic, interdependent systems. Findings in recent decades have encouraged a transition from research predominantly centered around monoamine neurotransmission to intracellular signaling, synaptic/neural plasticity, and other cellular mechanisms. C
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