Age-related changes in brain proDynorphin gene expression in the rat

doi:10.1016/j.neurobiolaging.2004.02.025

Neurobiology of Aging

Volume 25, Issue 10, November–December 2004, Pages 1343-1347

https://doi.org/10.1016/j.neurobiolaging.2004.02.025 Get rights and content

Abstract

Dynorphin has a well-established role in feeding and gustation. Alterations in taste perception and feeding behavior are common with age. We hypothesized that proDynorphin gene expression in brain areas involved in taste and feeding declines with age. Male Sprague-Dawley rats were housed individually with ad libitum access to food and water. Brain punches of the selected regions were dissected out in groups of rats aged 4–6, 12–14 and 18–21 months. ProDynorphin mRNA (measured using a cDNA probe) decreased significantly with age in arcuate nucleus and amygdala; increased significantly with age in hippocampus; and was not significantly affected in nucleus of the solitary tract, cortex, caudate putamen or hypothalamic paraventricular nucleus. These data suggest an age-related decrease in the synthesis of dynorphin in two brain regions strongly associated with feeding behavior, and an increase in dynorphin synthesis in a brain region associated with learning and memory.

Introduction

Opioid peptides are involved in behaviors that change across the lifespan, including reproduction, nociception, and feeding. A variety of studies have examined changes in CNS levels of enkephalin and β-endorphin, as well as gene expression of these peptides during aging. For example, several investigators report decreased levels of hypothalamic β-endorphin in aged Sprague-Dawley rats, and two of three also report decreased levels of hypothalamic enkephalin [7], [10], [28]. In Wistar rats β-endorphin levels decrease with aging in the striatum and hypothalamus, but met-enkephalin only decreases in the striatum [22]. To further complicate this issue, Wang et al. [44] noted that measures of brain opioid levels are dependent on the time of the day when the animal is sacrificed.

Opioid receptor binding also changes with aging. Nagahara et al. [32] found that enkephalin binding decreased with aging in hippocampal regions in Long-Evans rats. Several studies indicate that both mu and kappa opioid receptor binding are decreased in aged Sprague-Dawley rats in various brain regions, both hypothalamic and non-hypothalamic [26], [36]. The number of cells that synthesize proEnkephalin also decreases in the rostral striatum and shell of the nucleus accumbens of aged Fischer 344 rats [38].

Gene expression of proOpiomelanocortin (POMC) decreases in arcuate nucleus of several strains of aging rats [15], [25], [34]. The prohormone convertases that are involved in the processing of POMC also decrease in aged female C57BL/6J mice [18]. Little is known about the changes in proDynorphin that occur with aging. Aging did not affect proDynorphin gene expression in hypothalamus of C57BL/6J mice [39], but did result in increased proDynorphin mRNA in hippocampus of Long-Evans and Fischer 344 rats [17], [45].

Dynorphins have a well-established role in taste and feeding pathways, and alterations in taste perception and feeding behavior are common in the elderly, as evidenced by diminished desire to eat, in humans (7). Human studies suggest an age-related decrease in the desire to eat [4] whereas animal studies indicate increased satiation during meals with advancing age [1]. Aged animals also become less sensitive to the feeding modulatory effects of opioid agonists and antagonists with age [14], have reduced responses to sodium and water deprivation [40], and show differences in licking behavior in studies with sucrose solutions [27]. These studies suggest that aged animals exhibit alterations in taste and feeding behavior similar to that observed in humans. In the current study, we hypothesized that there is an overall decline in dynorphin gene expression due to age in specific dynorphin-containing brain areas with established roles in feeding. Based on the known distribution of proDynorphin in feeding associated brain sites [9], [16], [23], [33], [37], we measured the levels of proDynorphin mRNA in nucleus of the solitary tract (NTS), hypothalamic paraventricular nucleus (PVN), arcuate nucleus (Arc), caudate putamen (CP), cortex (CTX), hippocampus (HC) and amygdala (AMY) in rats at 4–6, 12–14 and 18–21 months of age.

Section snippets

Animals

Male Sprague-Dawley rats (Harlan, Madison, WI) were individually housed in standard hanging cages with a 12 h light/12 h dark photoperiod (lights on 07:00) in temperature-controlled rooms (21–22 °C). Teklad certified rat chow and water were allowed ad libitum. Animals were obtained from the vendor at age 2 months, and then housed until they reached the age under study. The aging of animals was timed such that there were 9–16 rats at each age group (4–6, 12–14 and 18–21 months) at the time of

Results

Table 1 shows body weight and mean daily food intake for each age-group. As shown in the table, there was a significant main effect of age on body weight between groups (F_2,31=16.615, P<0.0001, Table 1), with body weight increasing with age. ANOVA of the effect of age on average daily food intake among groups neared significance (F_2.31=2.383, P=0.0691, Table 1). Average daily food intake decreased with age and unpaired t-tests indicate that the 18–21 month old rats ate significantly less (P

Discussion

The present data indicate that proDynorphin gene expression is affected by age in a differential manner across brain site. Whereas proDynorphin gene expression in AMY and Arc significantly declined with age (Fig. 1A and B), proDynorphin gene expression in HC increased significantly (Fig. 1C), and no significant changes were observed in PVN, NTS, Ctx, or CP (data not shown). These age-induced decreases in brain proDynorphin gene expression is similar to that observed for the related opioid

Acknowledgements

We would like to thank Dr. Eun-mee Kim and Ms. Jacqueline Briggs for their expert technical assistance with the proDynorphin gene expression measurements. Supported by the Department of Veterans Affairs, the National Institute on Drug Abuse Grant DA03999 and the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK57573.

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Age-related changes in brain proDynorphin gene expression in the rat

Abstract

Introduction

Section snippets

Animals

Results

Discussion

Acknowledgements

Brain Res

Anal. Biochem

Behav. Neural Biol

Life Sci

Neurobiol. Aging

Brain Res

Life Sci

Neurobiol. Aging

Physiol. Behav

Brain Res

Brain Res. Bull

Physiol. Behav

Am. J. Clin. Nutr

Life Sci

Brain Res

Neurobiol. Aging

Neurosci. Lett

Anal. Biochem

Peptides

Neurobiol. Aging

Meal patterns associated with the age-related decline in food intake in the Fischer 344 rat

Am. J. Physiol

Evidence for the anorexia of aging: gastrointestinal transit and hunger in healthy elderly vs. young adults

Am. J. Physiol