Pathophysiology of Migraine: A Disorder of Sensory Processing

Physiological Reviews, Journal Year: 2017, Volume and Issue: 97(2), P. 553 - 622

Published: Feb. 9, 2017

Plaguing humans for more than two millennia, manifest on every continent studied, and with one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability planet. The pathophysiology has emerged from a historical consideration “humors” through mid-20th century distraction now defunct Vascular Theory to clear place neurological disorder. It could be said there are three questions: why, how, when? Why: is largely accepted inherited tendency brain lose control its inputs. How: classical trigeminal durovascular afferent pathway been explored laboratory clinic; interrogated immunohistochemistry functional imaging offer roadmap attack. When: attacks emerge due disorder sensory processing that itself likely cycles, influenced by genetics environment. In first, premonitory, phase precedes headache, stem diencephalic systems modulating signals, light-photophobia or sound-phonophobia, begin dysfunction eventually evolve pain time resolution postdromal phase. Understanding biology careful bench-based research led major classes therapeutics being identified: triptans, serotonin 5-HT 1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) antagonists; ditans, 1F agonists, CGRP mechanisms monoclonal antibodies; glurants, mGlu 5 modulators; promise come. Investment understanding very successful leaves us at new dawn, able transform impact global scale, well understand fundamental aspects human biology.

Language: Английский

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Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants

Nature Medicine, Journal Year: 2016, Volume and Issue: 22(3), P. 238 - 249

Published: March 1, 2016

Language: Английский

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Light as a central modulator of circadian rhythms, sleep and affect

Nature reviews. Neuroscience, Journal Year: 2014, Volume and Issue: 15(7), P. 443 - 454

Published: June 11, 2014

Language: Английский

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Psychedelics Promote Structural and Functional Neural Plasticity

Cell Reports, Journal Year: 2018, Volume and Issue: 23(11), P. 3170 - 3182

Published: June 1, 2018

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role pathophysiology depression and related disorders. The ability to promote both structural functional plasticity PFC has been hypothesized underlie fast-acting antidepressant properties dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable robustly increasing neuritogenesis and/or spinogenesis vitro vivo. These changes neuronal structure accompanied by increased synapse number function, as measured fluorescence microscopy electrophysiology. induced appear result from stimulation TrkB, mTOR, 5-HT2A signaling pathways could possibly explain clinical effectiveness these compounds. Our results underscore therapeutic potential and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds safe, effective, treatments

Language: Английский

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Social stress induces neurovascular pathology promoting depression

Nature Neuroscience, Journal Year: 2017, Volume and Issue: 20(12), P. 1752 - 1760

Published: Nov. 9, 2017

Language: Английский

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Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments

Neuron, Journal Year: 2019, Volume and Issue: 102(1), P. 75 - 90

Published: April 1, 2019

Language: Английский

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Sex-specific transcriptional signatures in human depression

Nature Medicine, Journal Year: 2017, Volume and Issue: 23(9), P. 1102 - 1111

Published: Aug. 21, 2017

Language: Английский

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A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications

Frontiers in Behavioral Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: July 3, 2018

Stress is recognized as an important issue in basic and clinical neuroscience research, based upon the founding historical studies by Walter Canon Hans Selye past century, when concept of stress emerged a biological adaptive perspective. A lot research after that period has expanded knowledge field. Since then, it was discovered response to stressful stimuli elaborated triggered the, now known, system, which integrates wide diversity brain structures that, collectively, are able detect events interpret them real or potential threats. However, different types stressors engage networks, requiring fine-tuned functional neuroanatomical processing. This integration information from stressor itself may result rapid activation Sympathetic-Adreno-Medullar (SAM) axis Hypothalamus-Pituitary-Adrenal (HPA) axis, two major components involved response. The complexity not restricted neuroanatomy SAM HPA axes mediators, but also diverge according timing duration exposure, well its short- and/or long-term consequences. identification neuronal circuits stress, their interaction with mediator molecules over time critical, only for understanding physiological responses, understand implications on mental health.

Language: Английский

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Nociception, Pain, Negative Moods, and Behavior Selection

Neuron, Journal Year: 2015, Volume and Issue: 87(3), P. 474 - 491

Published: Aug. 1, 2015

Language: Английский

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Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress

Proceedings of the National Academy of Sciences, Journal Year: 2014, Volume and Issue: 111(45), P. 16136 - 16141

Published: Oct. 20, 2014

Significance Depression and anxiety have been linked to increased inflammation. However, we do not know if inflammatory status predates onset of disease or whether it contributes depression symptomatology. We report preexisting individual differences in the peripheral immune system that predict promote stress susceptibility. Replacing a stress-naive animal’s with stressed animal increases susceptibility social including repeated defeat (RSDS) witness (a purely emotional form stress). Depleting cytokine IL-6 from whole body just leukocytes promotes resilience, as does sequestering outside brain. These studies demonstrate response can be generated blocked periphery, offer potential new treatment for disorders.

Language: Английский

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