title: From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer's Disease.
abstract: Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer's disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction.
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA chris.dulla@tufts.edu.
authors.forename: Chris G
authors.initials: CG
authors.lastname: Dulla
authors.affiliation: Department of Pediatrics and Neuroscience, University of Pennsylvania Perleman School of Medicine, Philadelphia, PA, USA Division of Neurology and the Research Institute of Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Coulter
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Jokubas
authors.initials: J
authors.lastname: Ziburkus
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D004827:Epilepsy / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D007473:Ion Channels; D016875:tau Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D058570:TOR Serine-Threonine Kinases
keywords: Alzheimer’s disease; circuits; epilepsy; molecular dysfunction; traumatic brain injury