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The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats were analyzed with Agilent's whole rat genome microarray. The RVLM gene expression profile varied with age, and an association between chronological age and specific RVLM gene expression patterns was observed [ P < 0.05, false discovery rate (FDR) < 0.3]. Functional analysis of RVLM microarray data via gene ontology profiling and pathway analysis identified upregulation of genes associated with immune- and stress-related responses and downregulation of genes associated with lipid biosynthesis and neurotransmission in aged compared with middle-aged and young rats. Differentially expressed genes associated with the complement system and microglial cells were further validated by quantitative PCR with separate RVLM samples ( P < 0.05, FDR < 0.1). The present results have identified age-related changes in the transcriptomic profile of the RVLM, modifications that may provide the molecular backdrop for understanding age-dependent changes in physiological regulation.

Whole body hyperthermia (WBH) has been used in experimental settings as an adjunct to radiochemotherapy for the treatment of various malignant diseases. The therapeutic effect of WBH has been hypothesized to involve activation of the immune system, although the effect of hyperthermia-induced activation of sympathetic nerve discharge (SND) on splenic immune function is not known. We tested the hypothesis that heating-induced splenic sympathoexcitation would alter splenic cytokine gene expression as determined using gene array and real-time RT-PCR analyses. Experiments were performed in splenic-intact and splenic-denervated anesthetized Sprague-Dawley rats (n=32). Splenic SND was increased during heating (internal temperature increased from 38 degrees to 41 degrees C) in splenic-intact rats but remained unchanged in nonheated splenic-intact rats. Splenic interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and growth-regulated oncogene 1 (GRO 1) mRNA expression was higher in heated than in nonheated splenic-intact rats. Splenic IL-1beta, IL-6, and GRO 1 mRNA expression was reduced in heated splenic-denervated compared with heated splenic-intact rats, but did not differ between heated splenic-denervated and nonheated splenic-intact rats. These results support the hypothesis that hyperthermia-induced activation of splenic SND enhances splenic cytokine gene expression.