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Microarray analysis of aging-associated immune system alterations in the Rostral Ventral Lateral Medulla of F344 rats

ABSTRACT: Progressive aging is associated with changes in sympathetic nervous system (SNS) regulation, suggesting an effect of advancing age on the functionality of central sympathetic premotor neurons. The rostral ventral lateral medulla (RVLM) contains sympathetic premotor neurons and plays a key role in SNS regulation, and it is plausible to speculate that age-related changes in the molecular mechanisms in the RVLM may contribute to alterations in SNS regulation. The present study tested the hypothesis that aging is associated with altered gene expression in the RVLM with emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats were analyzed using 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, FDR<0.3). Functional analysis of RVLM microarray data via gene ontology profiling and pathway analysis has identified up-regulation of genes associated with immune- and stress- related responses, and down-regulation of genes associated with lipid biosynthesis and neurotransmission in aged compared with middle-aged and young rats. Differentially expressed genes associated with complement system and microglial cells were further validated by quantitative PCR with separate RVLM samples (p<0.05, FDR<0.1). The present results are the first to demonstrate age-related changes in the RVLM molecular mechanisms, modifications that may provide the molecular backdrop for understanding immune-associated changes in SNS regulation. Overall design: Rostral Ventral Lateral Medulla (RVLM) tissue punches were collected from young (3 months old, 301±20 gm,n=3), middle-aged (12 months old, 423±18 gm,n=3) and aged (24 months old, 413±20 gm, n=3) male F344 rats. RNA collected from this tissue punches were analyzed using Agilent’s whole rat genome 4x44K microarray kit.

INSTRUMENT(S): Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Feature Number version)

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Sivasai Balivada  

PROVIDER: GSE90956 | GEO | 2016-12-07



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

Balivada Sivasai S   Ganta Chanran K CK   Zhang Yongqing Y   Pawar Hitesh N HN   Ortiz Richard J RJ   Becker Kevin G KG   Khan Arshad M AM   Kenney Michael J MJ  

Physiological genomics 20170616 8

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 gen  ...[more]

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