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.
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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
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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.
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The authors have no conflict of interest.
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Rao, J.S., Kellom, M., Kim, HW. et al. Neuroinflammation and Synaptic Loss. Neurochem Res 37, 903–910 (2012). https://doi.org/10.1007/s11064-012-0708-2
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DOI: https://doi.org/10.1007/s11064-012-0708-2