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Neuroinflammation and Synaptic Loss

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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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Correspondence to Jagadeesh S. Rao.

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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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