Analysis of RVLM Gene Expression in Young, Middle‐Aged and Aged F344 Rats

Abstract

Abstract: The rostral ventral lateral medulla (RVLM) plays a critical role in regulation of basal sympathetic nerve discharge (SND). Advanced age is associated with altered regulation of SND, however, the effect of age on central medullary mechanisms regulating SND remains unknown. A series of experiments were initiated to identify cellular and molecular targets that may mediate age‐related changes in medullary regulation of SND. We tested the hypothesis that aging shifts the balance of RVLM excitatory and inhibitory influences towards excitation. Gene expression analysis was performed using Agilent Whole Rat Genome Microarray 4×44K followed by validation of microarray with TaqMan real‐time RT‐PCR and immunoblotting for specific RVLM proteins. Total RNA and protein were extracted from RVLM micropunches from young, middle‐aged and aged F344 rats. Microarray analysis revealed up‐regulation in aged compared to young and middle‐aged rats of several genes related to immune function and neurotransmitter receptors. Specifically, the chemokines CCL3, CCL4 and CCL5 were up‐regulated 3 to 4 fold in aged rats compared to young and middle‐aged rats. The results of previous studies suggest that increased chemokines in the brain can modulate NMDA receptor responses. The current preliminary results suggest that increased chemokine gene expression in the RVLM of aged rats may contribute to age‐related changes in SND regulation. Supported by NIH A6‐041948.