Microarray analysis of aging-associated immune system alterations in the rostral ventrolateral medulla of F344 rats

Abstract

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 [ < 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 ( < 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.

Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice

“…Furthermore, DAVID ( Huang da et al, 2009 ) functional annotation shows that the majority of the up-regulated genes are associated with the innate and inflammatory immune responses ( Figure 1C ). Interestingly, the immune response-related functions were also found to have significant changes during aging ( High, 2004 ; Weinberger et al, 2008 ; Balivada et al, 2017 ), indicating that immune response-related genes may play important roles during the hippocampal aging process.…”

Does acute heat stress differentially-modulate expression of ionotropic neurotransmitter receptors in the RVLM of young and aged F344 rats?

“…Consistent with these findings, Sharma [36] observed no age-related changes in brainstem levels of GABA, glycine, and glutamate in non-heated adult rats. On the other hand, Balivada et al [2] reported upregulation of RVLM immune response-associated genes and pathways with advancing age in F344 rats, as well as age-related alterations in genes involved with lipid metabolism and transport, and neurotransmission. These findings suggest that aging may modify the basal expression of genes in the RVLM involved in key molecular pathways and functions, rather than influencing ionotropic receptor transcripts, modifications that may contribute to age-dependent changes in the diverse physiological systems served by this brainstem area.…”

“…Rats were divided into two groups, the first group of young (n=10) and aged (n=10) F344 rats was used for gene expression studies, and with second group of young (n=8) and aged (n=8) was used for immunoblotting studies. The brains collected from young and aged rats were subjected to brain sectioning and RVLM micropunching protocols that were performed as described in our previous manuscript [2]. The stereotaxic coordinate system along with its photographic documentation of histologically stained hindbrain sections of the rat brain atlas by Paxinos and Watson [31], were used as references to locate and identify the hindbrain region containing the RVLM.…”

“…To identify the RVLM sample area, a fiducial analysis was performed as discussed in our previous manuscript [2]. The micropunched sections (200μm) were stained with cresyl violet and examined for the location of the punched area relative to other landmarks such as, the fourth ventricle (4V), spinal trigeminal tract (sp5), inferior olive (IO) and pyramidal tract (py), and dorsal compact formation of the nucleus ambiguus (AmbC).…”

Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees

“…Such reasons include the need for investigators to survey the effects of factors that produce global, whole-organism or whole-subdivision effects that are poorly understood at a regional or cellular level. These include environmental agents [257], pharmacological interventions [200], ontogenic state (e.g., see introductory remarks in [27]), or physiological processes. J. Miller et al (2014) [281] examined various hypothalamic sub-regions within the context of a hemispheric tissue analysis in prenatal human brain using high throughput transcriptomic methods.…”