Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]

Background Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the curre...

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Main Authors: Marcus Picard-Mareau, Markus Rueckels
Format: Article
Language:English
Published: F1000 Research Ltd 2025-01-01
Series:F1000Research
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Online Access:https://f1000research.com/articles/11-1405/v3
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author Marcus Picard-Mareau
Markus Rueckels
author_facet Marcus Picard-Mareau
Markus Rueckels
author_sort Marcus Picard-Mareau
collection DOAJ
description Background Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.
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spelling doaj-art-c1a0598341b84b61b227a0dfbfdf85e72025-01-17T01:00:00ZengF1000 Research LtdF1000Research2046-14022025-01-0111176677Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]Marcus Picard-Mareau0Markus Rueckels1https://orcid.org/0000-0001-6775-0437Lisa-Kolk-Stiftung, Berg. Neukirchen, North Rhine Westphalia, 51381, GermanyLisa-Kolk-Stiftung, Berg. Neukirchen, North Rhine Westphalia, 51381, GermanyBackground Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.https://f1000research.com/articles/11-1405/v3Behavioral conditioning NK cells gene expression analysis HPA axis poly I:C campher smelleng
spellingShingle Marcus Picard-Mareau
Markus Rueckels
Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]
F1000Research
Behavioral conditioning
NK cells
gene expression analysis
HPA axis
poly I:C
campher smell
eng
title Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]
title_full Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]
title_fullStr Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]
title_full_unstemmed Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]
title_short Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study [version 3; peer review: 1 approved, 3 approved with reservations]
title_sort differential gene expression during recall of behaviorally conditioned immune enhancement in rats a pilot study version 3 peer review 1 approved 3 approved with reservations
topic Behavioral conditioning
NK cells
gene expression analysis
HPA axis
poly I:C
campher smell
eng
url https://f1000research.com/articles/11-1405/v3
work_keys_str_mv AT marcuspicardmareau differentialgeneexpressionduringrecallofbehaviorallyconditionedimmuneenhancementinratsapilotstudyversion3peerreview1approved3approvedwithreservations
AT markusrueckels differentialgeneexpressionduringrecallofbehaviorallyconditionedimmuneenhancementinratsapilotstudyversion3peerreview1approved3approvedwithreservations