1.
Molecular Signatures of HIV-1 Envelope Associated with HIV-Associated Neurocognitive Disorders.
Evering, TH
Current HIV/AIDS reports. 2018;(1):72-83
Abstract
PURPOSE OF REVIEW The HIV-1 envelope gene (env) has been an intense focus of investigation in the search for genetic determinants of viral entry and persistence in the central nervous system (CNS). RECENT FINDINGS Molecular signatures of CNS-derived HIV-1 env reflect the immune characteristics and cellular constraints of the CNS compartment. Although more readily found in those with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular signatures distinguishing CNS-derived quasispecies can be identified early in HIV-1 infection, in the presence or absence of combination antiretroviral therapy (cART), and are dynamic. Amino acid signatures of CNS-compartmentalization and HAND have been identified across populations. While some significant overlap exists, none are universal. Detailed analyses of CNS-derived HIV-1 env have allowed researchers to identify a number of molecular determinants associated with neuroadaptation. Future investigations using comprehensive cohorts and longitudinal databases have the greatest potential for the identification of robust, validated signatures of HAND in the cART era.
2.
Histamine and Migraine.
Yuan, H, Silberstein, SD
Headache. 2018;(1):184-193
Abstract
BACKGROUND Histamine is an ancient "tissue amine" preceding multicellular organisms. In the central nervous system (CNS), its fibers originate solely from the tuberomammillary nucleus and travel throughout the brain. It is mainly responsible for wakefulness, energy homeostasis, and memory consolidation. Recently, several studies suggest a potential role of histamine in migraine pathogenesis and management. METHODS Narrative review of current literature regarding histamine and migraine. RESULTS Histamine plays a crucial role in migraine pathogenesis: sustaining the neurogenic inflammation pathway. Interaction between mast cells (MC) and calcitonin-gene related protein (CGRP) results in sensitization of trigeminal afferents and trigeminal ganglia (TG). Histamine binds with differing affinities to four different histaminergic G-protein coupled receptors, activating protein kinases, or triggering calcium release with subsequent mode of actions. Histamine 1 receptor (H1 R) and histamine 2 receptor (H2 R) antagonists are frequently used for the treatment of allergy and gastric acid secretion, respectively, but their antagonism is probably ineffective for migraine. Histamine 3 receptor (H3 R) and histamine 4 receptor (H4 R) have a threefold higher affinity than H1 R/H2 R for histamine and are found almost exclusively on neurons and immune tissues, respectively. H3 R acts as an autoreceptor or as a heteroreceptor, lowering the release of histamine and other neurotransmitters. This is a potential target for anti-nociception and anti-neurogenic inflammation. To date, several small clinical trials using low dose histamine or Nα -methylhistamine have demonstrated migraine prophylactic efficacy, probably via H3 R or other undetermined pathways. CONCLUSION The histamine system interacts with multiple regions in the CNS and may hypothetically modulate the migraine response. Low dose histamine may be a promising option for migraine prevention.