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Neurochemical Research

, Volume 37, Issue 5, pp 903–910 | Cite as

Neuroinflammation and Synaptic Loss

  • Jagadeesh S. RaoEmail author
  • Matthew Kellom
  • Hyung-Wook Kim
  • Stanley I. Rapoport
  • Edmund A. Reese
Overview

Abstract

Neuroinflammation plays a critical role in the progression of many neurodegenerative, neuropsychiatric and viral diseases. In neuroinflammation, activated microglia and astrocytes release cytokines and chemokines as well as nitric oxide, which in turn activate many signal transduction pathways. The cytokines, interleukin-1 beta and tumor necrosis factor alpha, regulate transcription of a number of genes within the brain, which can lead to the formation of pro-inflammatory products of the arachidonic acid cascade. Formation of pro-inflammatory agents and associated cytotoxic products during neuroinflammation can be detrimental to neurons by altering synaptic proteins. Neuroinflammation as well as excitotoxic insults reduce synaptic markers such as synaptophysin and drebrin. Neurodegenerative, neuropsychiatric illnesses and viral infections are accompanied by loss of both pre- and post-synaptic proteins. These synaptic changes may contribute to the progressive cognitive decline and behavioral changes associated with these illnesses.

Keywords

Arachidonic acid Cytokines Drebrin Synaptophysin Excitotoxicity 

Abbreviations

AA

Arachidonic acid

AD

Alzheimer’s disease

AP

Activator protein

BD

Bipolar disorder

CNS

Central nervous system

DHA

Docosahexaenoic acid

GFAP

Glial fibrillary acidic protein

HAD

HIV-associated dementia

HIV

Human immunodeficiency virus

HNE

4-hydroxy-2-nonenal

IFN

Interferon

IL-1β

Interleukin-1β

iNOS

Inducible nitric oxide synthase

IP

Inducible protein

LPS

Lipopolysaccharide

MCI

Mild cognitive impairment

NF-κB

Nuclear factor-kappa B

NMDA

N-methyl-d-aspartic acid

nNOS

Neuronal nitric oxide synthase

NO

Nitric oxide

PI

Phosphatidylinositol

PUFA

Polyunsaturated fatty acid

SAM

Senescence-accelerated mice

SZ

Schizophrenia

TNFα

Tumor necrosis factor α

Notes

Acknowledgments

This research was entirely supported by the Intramural Research Programs of the National Institute on Aging, National Institutes of Health, Bethesda, MD 20892. We thank the National Cancer Institute (NCI), Center for Cancer Research (CCR) Fellows Editorial Board for proofreading the manuscript.

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  • Jagadeesh S. Rao
    • 1
    Email author
  • Matthew Kellom
    • 1
  • Hyung-Wook Kim
    • 1
  • Stanley I. Rapoport
    • 1
  • Edmund A. Reese
    • 1
  1. 1.Brain Physiology and Metabolism Section, National Institute on AgingNational Institutes of HealthBethesdaUSA

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