Electrophysiological and Endocrinological Aspects of Aging in the Rat Pineal Gland

: Both plasma melatonin levels and hypothalamic arcuate nucleus pro‐opiomelanocortin (POMC) (biosynthetic precursor to the endogenous opioid ß‐endorphin and other opiomelanocortins) mRNA content decrease with aging. To test whether the decline in melatonin is responsible for the decline in POMC mRNA, we investigated the effects of daily melatonin treatment on hypothalamic POMC mRNA content in middle‐aged and older Sprague–Dawley rats. Daily nocturnal melatonin treatment (50 μg kg bw−1 night−1, in the night‐time drinking water) for 7 months, starting at 13 months of age, did not significantly alter female arcuate nucleus POMC mRNA content determined at the end of the light period (i.e., before nightly melatonin administration), but suppressed (24%, P < 0.05) POMC mRNA content at the end of the dark period (i.e., following melatonin administration). Likewise, nocturnal administration of 50 or 500 μg melatonin kg bw−1 night−1 to male rats for 7 months suppressed (31 or 28%, respectively; P < 0.05) POMC mRNA content at the middle of the dark period at 20 months of age. Finally, 10 wk administration of 30 μg melatonin kg bw−1 day−1 suppressed (31%, P < 0.01) POMC mRNA content in middle‐aged male rats killed at the end of the dark period. Melatonin treatments did not significantly alter estradiol or testosterone levels. Thus, moderate‐dosage nocturnal melatonin supplementation suppressed nocturnal hypothalamic POMC gene expression in both middle‐aged males and females, suggesting that melatonin supplementation during aging decreases, rather than increases, forebrain opiomelanocortinergic activity. These POMC responses were apparently not dependent on gonadal steroid responses and did not become refractory to melatonin treatment maintained until old age.

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Suppression of hypothalamic pro‐opiomelanocortin (POMC) gene expression by daily melatonin supplementation in aging rats

Rasmussen

Marck

Boldt

et al. 2003

“…A disappearance of day-night rhythm of melatonin in old and Alzheimer patients has been reported by Skene et al (1990). A decrease of pineal activity (Reuss et al, 1986), I accepted October 18, 1994 has been reported in old male rats (Reuss, 1980). We recently related the increase in the calcium content of pineal glands of aging rats (Humbert and PCvet, 1991) and the appearance of calcium concretions which have been reported earlier by Quay (1974).…”

Section: Introductionmentioning

confidence: 70%

“…This phenomenon may be linked to the decrease in electrical activity in old rats (Reuss et al, 1986), to the reduction of sympathetic innervation in aging animals, and the decline of the density of b-adrenergic receptors on pinealocytes membranes (Greenberg and Weiss, 1978;Henden et al, 1992), leading to a reduction of the metabolic activity of the gland.…”

Section: Cytoplasm Lp Cytoplasm Dp Mitochondria Dpmentioning

confidence: 99%

The pineal gland of the aging rat: Calcium localization and variation in the number of pinealocytes

Humbert¹,

Pévet²

1995

In the present study, we investigated the population of pinealocytes in the pineal gland of aging rats. Dark and light pinealocytes were analyzed as to their calcium content. Calcium localization was realized in dark and light cells by means of cytochemistry and X-ray microanalysis. Calcium was mainly localized in dark pinealocytes characterized by many ultrastructural signs of degeneration. The number of pinealocytes per square surface of aged rats (28 months) was compared to young ones (3-4 months). While there is a significant increase in the number of dark pinealocytes there is a decrease in the total number of pinealocytes in aged rats. This age-related loss of pinealocytes may explain the age-related functional decline of the pineal gland activity (e.g., the decrease of the nocturnal melatonin production).

“…Previous reports indicate that nocturnal pineal melatonin content, as well as melatonin concentrations in circulation, decrease with aging in the rat [Reiter et al, 1981;Reuss et al, 1986;Pang et al, 1990;Bondarenko, 1992;Selmaoui and Touitou, 1999]. Pineal melatonin content in the middle-aged (12-month-old) female rat is intermediate between that of young adult and old rats [Reiter et al, 1981].…”

Section: Discussionmentioning

confidence: 96%

Aging‐dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses

Rasmussen

Mitton

Larsen

et al. 2001

Pineal melatonin secretion has been reported to commonly decrease with aging, whereas intra-abdominal adiposity, plasma insulin and plasma leptin levels tend to increase. We recently demonstrated that daily melatonin administration starting at middle age suppressed male rat intra-abdominal fat, plasma leptin and plasma insulin to youthful levels, suggesting that aging-related changes in pineal melatonin secretion and in energy regulation may be functionally related. Accordingly, we have now investigated the effects of daily melatonin treatment on energy regulation in young versus middle-aged male Sprague Dawley rats. Addition of melatonin to the drinking water (0.2 microg/mL) produced nocturnal and diurnal plasma melatonin concentrations in middle-aged rats (12 months) equivalent to those of young adult (5 months) rats. Administration of this melatonin dosage every day for 10 wk starting at 10 months of age suppressed (P < 0.01) relative intra-abdominal fat, non-fasted plasma insulin and plasma leptin by 27, 39, and 51%, respectively (vs. vehicle-treated controls). In contrast, administration of melatonin for 10 wk starting at 3 months of age did not significantly alter (P> 0.10) any of these parameters. The melatonin administration stimulated (102%, P < 0.001) behavioral responsiveness of the middle-aged rats in a test of response to novelty, restoring youthful levels, but did not significantly alter behavioral responsiveness of the young rats. These results suggest that suppression of intra-abdominal adiposity and plasma leptin and insulin levels and stimulation of behavioral responsiveness in response to daily exogenous melatonin begins at middle age, coincident with and likely dependent upon the aging-associated decline in endogenous pineal melatonin secretion. These results further suggest that appropriate melatonin supplementation may potentially provide therapy or prophylaxis not only for the insulin resistance, increased intra-abdominal fat and resulting pathologies that occur with aging, but also for some aging-associated behavioral changes.