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


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.


Arachidonic acid Cytokines Drebrin Synaptophysin Excitotoxicity 



Arachidonic acid


Alzheimer’s disease


Activator protein


Bipolar disorder


Central nervous system


Docosahexaenoic acid


Glial fibrillary acidic protein


HIV-associated dementia


Human immunodeficiency virus








Inducible nitric oxide synthase


Inducible protein




Mild cognitive impairment


Nuclear factor-kappa B


N-methyl-d-aspartic acid


Neuronal nitric oxide synthase


Nitric oxide




Polyunsaturated fatty acid


Senescence-accelerated mice




Tumor necrosis factor α



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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