A longitudinal study of age-related loss of noradrenergic nerves and lymphoid cells in the rat spleen.
A longitudinal study of sympathetic noradrenergic (NA) innervation of the spleen was carried out in 3-, 8-, 12-, 17-, 21-, and 27-month-old Fischer 344 (F344) rats using (i) fluorescence histochemistry for localization of norepinephrine (NE); (ii) immunocytochemistry (ICC) for localization of tyrosine hydroxylase (TH)-positive nerve fibers alone, and in combination with specific markers for T and B lymphocytes (OX19 and anti-mu respectively), and macrophages (ED3); and (iii) high-performance liquid chromatography with electrochemical detection for quantitation of NE. Fluorescence histochemistry revealed extensive loss of NA nerve fibers in all compartments of the spleen in 21- and 27-month-old rats. With single-label ICC, a decline in TH+ nerve fibers in all compartments of the spleen was observed by 17 months of age and became more severe with advancing age; these findings suggest that both the rate-limiting enzyme and the transmitter itself (NE) are depleted from sympathetic nerves in aged rat spleen. Double-label ICC demonstrated the loss of TH+ nerve fibers in spleen from 17-, 21-, and 27-month-old rats, and a parallel loss of OX19+ T lymphocytes and ED3+ macrophages in these cellular compartments. Neurochemical measurement of NE demonstrated a decline in NE per wet weight at 27 months of age. The age-related decline in NA innervation of spleen and in the density of specific populations of cells of the immune system (T lymphocytes and antigen-presenting ED3+ macrophages), that follow remarkably similar time courses, supports functional evidence for dynamic interactions between the immune system and NA sympathetic nerves in the spleen, and further suggests a causal relationship between these age-related phenomena, i.e., that age-related immunosenescence promotes sympathetic denervation of the spleen which further compromises immune function. This hypothesis, however, requires further testing.
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, New York 14642.
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DL
Bellinger
K D
KD
Ackerman
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SY
Felten
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DL
Felten
D000375:Aging; D000818:Animals; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D009638:Norepinephrine / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000737:chemistry / Q000166:cytology*; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry
D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine