149. Lowering splenic sympathetic activity by chronic rilmenidine treatment fails to restore sympathetic neurotransmission in spleens from aging brown norway rats

149. Lowering splenic sympathetic activity by chronic rilmenidine treatment fails to restore sympathetic neurotransmission in spleens from aging brown norway rats

In rodent models and humans, sympathetic dysfunction in immune organs occurs concomitantly with immune senescence. Our previous studies in Brown Norway (BN rats) a commonly used aging model, indicate splenic sympathetic nerve activity (SNA) is elevated. This is accompanied by sympathetic nerve loss,...

Full description

Saved in:
Bibliographic Details
Published in:Brain, behavior, and immunity Vol. 40; p. e43
Main Authors: Lorton, D, Perez, S.D, Molinaro, C, Thyagarajan, S, Ghamsary, M, Lubahn, C.L, Bellinger, D.L
Format: Journal Article
Language:English
Published: Elsevier Inc 01-09-2014
Subjects:
Allergy and Immunology
Psychiatry
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In rodent models and humans, sympathetic dysfunction in immune organs occurs concomitantly with immune senescence. Our previous studies in Brown Norway (BN rats) a commonly used aging model, indicate splenic sympathetic nerve activity (SNA) is elevated. This is accompanied by sympathetic nerve loss, and uncoupling of beta-adrenergic receptors (beta-AR) to cAMP in splenocytes. We tested the hypothesis that increased SNA in the aging spleen contributes to sympathetic dysfunction in BN rats. Male BN rats (15-month-old, M) received 0, 0.5 or 1.5 μ g/kg/day rilmenidine intraperitoneally for 90 days to chronically lower splenic SNA. Untreated 3 M and 18 M BN rats controlled for aging and stress effects. We evaluated splenic norepinephrine (NE) turnover and plasma and splenic catecholamines levels using HPLC and a NE synthesis blocker. Splenic sympathetic innervation was assessed with histofluorescence. Beta-AR density and beta-AR-stimulated cAMP production were determined by binding assays and ELISA, respectively. Splenic NE concentration or total content did not differ between rilmenidine, 3 M or 18 M control groups. However, rilmenidine dose-dependently reduced splenic NE turnover and circulating NE and modestly reversed splenic sympathetic neuropathy. Rilmenidine also increased beta-AR density in splenocytes, without affecting affinity, but had no effect on the age-related impairment of beta-AR-stimulated cAMP production. Thus, lowering SNA in the aging BN rat spleen does not prevent sympathetic neuropathy or restore beta-AR signaling via cAMP in splenic lymphocytes.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2014.06.169