Disease-Induced Neuroinflammation and Depression

Author(s): Cristina Benatti, Joan M.C. Blom, Giovanna Rigillo, Silvia Alboni, Francesca Zizzi, Riccardo Torta, Nicoletta Brunello, Fabio Tascedda.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 15 , Issue 4 , 2016

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Abstract:

Progression of major depression, a multifactorial disorder with a neuroinflammatory signature, seems to be associated with the disruption of body allostasis. High rates of comorbidity between depression and specific medical disorders, such as, stroke, chronic pain conditions, diabetes mellitus, and human immunodeficiency virus (HIV) infection, have been extensively reported. In this review, we discuss how these medical disorders may predispose an individual to develop depression by examining the impact of these disorders on some hallmarks of neuroinflammation known to be impaired in depressed patients: altered permeability of the blood brain barrier, immune cells infiltration, activated microglia, increased cytokines production, and the role of inflammasomes.

In all four pathologies, blood brain barrier integrity was altered, allowing the infiltration of peripheral factors, known to activate resident microglia. Evidence indicated morphological changes in the glial population, increased levels of circulating pro-inflammatory cytokines or increased production of these mediators within the brain, all fundamental in neuroinflammation, for the four medical disorders considered. Moreover, activity of the kynurenine pathway appeared to be enhanced. With respect to the inflammasome NLRP3, a new target whose role in neuroinflammation is emerging as being important, accumulating data suggest its involvement in the pathogenesis of brain injury following stroke, chronic pain conditions, diabetes mellitus or in HIV associated immune impairment.

Finally, data gathered over the last 10 years, indicate and confirm that depression, stroke, chronic pain, diabetes, and HIV infection share a combination of underlying molecular, cellular and network mechanisms leading to a general increase in the neuroinflammatory burden for the individual.

Keywords: Neuroinflammation, allostasis, depression, stroke, chronic pain, diabetes mellitus, human immunodeficiency virus infection, pro-inflammatory cytokines, blood brain barrier permeability, microglia, tryptophan catabolites, inflammasome.

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Article Details

VOLUME: 15
ISSUE: 4
Year: 2016
Page: [414 - 433]
Pages: 20
DOI: 10.2174/1871527315666160321104749
Price: $58

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