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.

20220902 Affymetrix all tissues all timepoints red green incl p v2: Differential gene expression of microarray data from rat hypothalamus, pituitary, adrenal gland, and spleen 0, +3h, +6h, +24h and +48h post recall, test, positive control, and negative control. Contains gene smybol, description, neurotransmitter group (NTM), chromosome, genomic position, group, sample ID and Affymmetrix transcript cluster ID. All data as single point RMA nomalized levels, plus averaged expression test vs. negative and positive vs. negative all 5 time points, first 3 time points and max/minx expression across all 5 time points plus test - negative and positive - negative across all tissues and time points, respectively 20220803 Ct values and Affymetrix correlation v2 Alignment of 32 genes between qRT-PCT Ct values (35 - Ct) and corresponding Affymetrix gene expression. Contains gene symbol, correlation qRT-PCR vs. Affymetrix for each gene, alias, refseq#, official full name, Qiagen catalog number, sample. Correlation: pivot data of all data points qRT-PCR and Affymetrix, linear regression incl. trendline across all data points