Inbred Substrain Differences Influence Neuroimmune Response and Drinking Behavior.
Alcohol Drinking
/ genetics
Animals
Behavior, Animal
Central Nervous System Depressants
/ administration & dosage
Ethanol
/ administration & dosage
Immunity, Innate
/ genetics
Interferon Inducers
/ pharmacology
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Mice, Transgenic
Models, Animal
Neuroimmunomodulation
/ genetics
Poly I-C
/ pharmacology
Alcohol
C57BL/6J
C57BL/6N
Neuroimmune
Poly I:C
TLR3
Journal
Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
06
03
2020
revised:
03
06
2020
accepted:
22
06
2020
pubmed:
9
7
2020
medline:
8
10
2021
entrez:
9
7
2020
Statut:
ppublish
Résumé
The inbred mouse strain C57BL/6 is widely used in both models of addiction and immunological disease. However, there are pronounced phenotypic differences in ethanol (EtOH) consumption and innate immune response between C57BL/6 substrains. The focus of this study was to examine the effects of substrain on innate immune response and neuroimmune-induced escalation of voluntary EtOH consumption. The main goal was to identify whether substrain differences in immune response can account for differences in EtOH behavior. We compared acute innate immune response with a viral dsRNA mimic, polyinosinic:polycytidylic acid (poly(I:C)), in brain using qRT-PCR in both C57BL/6N and C57BL/6J mice. Next, we used a neuroimmune model of escalation using poly(I:C) to compare drinking behavior between substrains. Finally, we compared brain neuroimmune response with both EtOH and repeated poly(I:C) in both substrains as a way to account for differences in EtOH behavior. We found that C57BL/6 substrains have differing immune response and drinking behaviors. C57BL/6N mice have a shorter but more robust inflammatory response to acute poly(I:C). In contrast, C57BL/6J mice have a smaller but longer-lasting acute immune response to poly(I:C). In our neuroimmune-induced escalation model, C57BL/6J mice but not C57BL/6N mice escalate EtOH intake after poly(I:C). Finally, only C57BL/6J mice show enhanced proinflammatory transcript abundance after poly(I:C) and EtOH, suggesting that longer-lasting immune responses are critical to neuroimmune drinking phenotypes. Altogether, this work has elucidated additional influences that substrain has on both innate immune response and drinking phenotypes. Our observations highlight the importance of considering and reporting the source and background used for production of transgenic and knockout mice. These data provide further evidence that genetic background must be carefully considered when investigating the role of neuroimmune signaling in EtOH abuse.
Sections du résumé
BACKGROUND
The inbred mouse strain C57BL/6 is widely used in both models of addiction and immunological disease. However, there are pronounced phenotypic differences in ethanol (EtOH) consumption and innate immune response between C57BL/6 substrains. The focus of this study was to examine the effects of substrain on innate immune response and neuroimmune-induced escalation of voluntary EtOH consumption. The main goal was to identify whether substrain differences in immune response can account for differences in EtOH behavior.
METHODS
We compared acute innate immune response with a viral dsRNA mimic, polyinosinic:polycytidylic acid (poly(I:C)), in brain using qRT-PCR in both C57BL/6N and C57BL/6J mice. Next, we used a neuroimmune model of escalation using poly(I:C) to compare drinking behavior between substrains. Finally, we compared brain neuroimmune response with both EtOH and repeated poly(I:C) in both substrains as a way to account for differences in EtOH behavior.
RESULTS
We found that C57BL/6 substrains have differing immune response and drinking behaviors. C57BL/6N mice have a shorter but more robust inflammatory response to acute poly(I:C). In contrast, C57BL/6J mice have a smaller but longer-lasting acute immune response to poly(I:C). In our neuroimmune-induced escalation model, C57BL/6J mice but not C57BL/6N mice escalate EtOH intake after poly(I:C). Finally, only C57BL/6J mice show enhanced proinflammatory transcript abundance after poly(I:C) and EtOH, suggesting that longer-lasting immune responses are critical to neuroimmune drinking phenotypes.
CONCLUSIONS
Altogether, this work has elucidated additional influences that substrain has on both innate immune response and drinking phenotypes. Our observations highlight the importance of considering and reporting the source and background used for production of transgenic and knockout mice. These data provide further evidence that genetic background must be carefully considered when investigating the role of neuroimmune signaling in EtOH abuse.
Identifiants
pubmed: 32640038
doi: 10.1111/acer.14410
pmc: PMC7722067
mid: NIHMS1621343
doi:
Substances chimiques
Central Nervous System Depressants
0
Interferon Inducers
0
Ethanol
3K9958V90M
Poly I-C
O84C90HH2L
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1760-1768Subventions
Organisme : NIAAA NIH HHS
ID : F31 AA025499
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA020926
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA012404
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA006399
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013520
Pays : United States
Informations de copyright
© 2020 by the Research Society on Alcoholism.
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