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Alcohol Clin Exp Res. 2019 Oct 7. doi: 10.1111/acer.14209. [Epub ahead of print]

Time course of blood and brain cytokine/chemokine levels following adolescent alcohol exposure and withdrawal in rats.

Author information

1
Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
2
Infectious and Inflammatory Disease Center and National Cancer Institute (NCI)-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Research Institute, La Jolla, CA, 92037, USA.
3
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
4
Dorris Neuroscience Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Abstract

BACKGROUND:

Adolescence is a critical period for neural development and alcohol exposure during adolescence can lead to an elevated risk for health consequences as well as alcohol use disorders. Clinical and experimental data suggest that chronic alcohol exposure may produce immunomodulatory effects that can lead to the activation of proinflammatory cytokine pathways as well as microglial markers. The present study evaluated, in brain and blood, the effects of adolescent alcohol exposure and withdrawal on microglia and on the most representative pro and anti-inflammatory cytokines and major chemokines that can contribute to the establishing of a neuroinflammatory environment.

METHODS:

Wistar rats (males, n=96) were exposed to ethanol vapors, or air control, for 5 weeks over adolescence (PD 22-58). Brains and blood samples were collected at three time points: 1) after 35 days of vapor/air exposure (PD58); 2) after 1 day of withdrawal (PD59), and 3) 28 days after withdrawal (PD86). The ionized calcium binding adapter molecule 1 (Iba-1) was used to index microglia activation, and cytokine/chemokine responses were analyzed using Magnetic Bead Panels.

RESULTS:

After 35 days of adolescent vapor exposure, a significant increase in Iba-1 immunoreactivity was seen in: amygdala, frontal cortex, hippocampus and substantia nigra. However, Iba-1 density returned to control levels at both 1 day and 28 days of withdrawal except in the hippocampus where Iba-1 density was significantly lower than controls. In serum, adolescent ethanol exposure induced a reduction of IL-13 and an increase in fractalkine at day 35. After 1 day of withdrawal IL-18 was reduced, and IP-10 was elevated, whereas both IP-10 and IL-10 were elevated at 28 days following withdrawal. In the frontal cortex adolescent ethanol exposure induced an increase of IL-1β at day 35, and 28 days of withdrawal, and IL-10 was increased after 28 days of withdrawal.

CONCLUSION:

These data demonstrate that ethanol exposure during adolescence produces significant microglial activation, however, inflammatory markers seen in the blood appear to differ from those observed in the brain.

KEYWORDS:

Wistar rats; adolescent; alcohol; cytokines; microglial activation

PMID:
31589333
DOI:
10.1111/acer.14209

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