Developmental pattern of tachykinins during aging in several organs: effect of exogenous melatonin
Introduction
Mammalian tachykinins (TKs), neurokinin A (NKA), and substance P (SP) are neuropeptides widely distributed in the CNS and other organs. The primary function of these peptides are not completely understood [30]. Through their effects on the vascular tone, they are potential regulators of the basal blood flow and therefore of the function of many organs and tissues [7]. It has been suggested that neurokinins may play an important role in the regulation of autonomic nervous system [34] as well as in modulation of the immune system [37]. SP, among other peptides, may contribute to the local vascular control in the ovary and there may be a relationship between ovulation and vascular endothelial function [44]. Neuropeptides are also particularly important in the coordination of pancreatic exocrine and endocrine secretions. Calcitonin gene-related peptide (CGRP), inmunoreactive neurons and CGRP/SP TKs immunoreactive fibers regulate hepatobiliary activity, including hemodynamic functions of the hepatic vasculature [20]. In addition, binding sites for SP and NKA neuropeptides have been localized in primary afferent nerves which innervate several immune organs including the thymus, spleen, and lymph nodes [16].
Little is known, however, of the developmental pattern of TKs in these organs. Few studies have addressed age-related changes in TKs in non-endocrine tissues, and data on the function and changes in neurokinins during the physiological aging process are limited and the results are conflicting. Reportedly, aging of the CNS has been associated with widespread changes in TK gene expression, suggesting that alterations in tachyninergic system may have implications for the physiopathology of the diseases of the elderly [35].
Aging of the nervous system has not been associated with widespread changes in TK binding but differences in behavioral responses to TK agonists may reflect changes in other transmitter systems which respond to TK input [43]. Finally, in the immunohistochemical study of the brain of young (5 months) versus middle-aged (15 months) and old rats (23–25 months) there was no statistically significant change in neuronal number and size of the neurokinin B and neurokinin-3 receptor staining [27]. The numbers of SP-LI perikarya in the central nervous system of aged hamsters at both day- and night-time were augmented three- to four-fold when compared to adults animals [40]. Recent studies from our laboratory have shown that during aging of the rats, concentrations of TKs in brain areas undergo important alterations, showing increased NKA and SP concentrations in hypothalamus of old rats in comparison to young or middle-aged rats and an opposite developmental pattern in pineal and striatum in which TK concentrations decreased with increasing age [18]. Melatonin treatment restored TK concentrations in hypothalamus of old rats showing values similar to those found in young rats. Striatal or pineal TK concentrations were not modified.
As in blood, levels of melatonin in every other fluid, tissue, and cell thus far studied are higher during the night than during the day [38]. Whereas the 24-h rhythm of melatonin is robust in young animals and humans, the cycle deteriorates during aging and may be totally abolished in neurodegenerative diseases [4], [41]. In the present study we investigated the effects of aging on the concentration of NKA and SP in different body organs. Since melatonin treatment has known [17], [23] to have a beneficial effect in a variety experimental neurodegenerative processes. The indication is that exogenous melatonin may delay the aging process of tissues by means of its free radical scavenging effects [21], [31]. Herein we investigated the possibility that melatonin may also influence TK concentrations in different body organs during aging.
Section snippets
Animals and treatments
Young (3 months) (N=49), middle-aged (13 months) (N=29) and old (23 months) female Wistar rats (N=32) from our colony were used. Animals were housed under 12 h light/dark cycles (lights on at 08:00 h) at a room temperature of approximately 23 °C. Standard rat chow and tap water were available ad libitum. The rats were divided into two groups: control and melatonin-treated. Young–control (N=26), young–MEL (N=23), middle-aged–control (N=15), middle-aged–MEL (N=14), old–control (N=15) and old–MEL (N
Ovaries
NKA concentrations in control and melatonin-treated groups did not show significant differences for the three ages studied. Only significant lower values (P<0.01) in the old–MEL as compared to old–control group were found. SP concentrations in the old–control group showed significantly increased (P<0.01) values as compared to young– and middle-aged–control groups. Melatonin treatment resulted in lower SP concentrations in the old–MEL female rats than in old–control rats and consequently
Discussion
The present results reveal that low concentrations of NKA and SP are present in the rat ovary regardless of their age. No significant differences in ovarian NKA concentrations in the three age groups studied were found. There are few reports on the role of TKs in the ovary, but some indicate that these peptides are present in the ovary and they may affect the secretion of ovarian steroids [7]. SP is involved in the neuroendocrine role of hypothalamo–pituitary–gonadal axis [9], [10], [28].
Acknowledgements
This work has been supported for the Spanish Ministry of Health, Fondo de Investigación Sanitaria. FIS No. 97/0988. The authors wish to express their gratitude to Dr. Reiter, University of Texas, Health Science Center at San Antonio, San Antonio, TX, USA, for his help in the English edition.
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