Changes in 5-HT7 serotonin receptor mRNA expression with aging in rat brain

Kohen, Ruth; Heidmann, Doris; Anthony, Joanne; White, Sylvia S.; Hamblin, Mark W.; Szot, Patricia

doi:10.1016/s0169-328x(00)00103-0

Cited by 13 publications

(8 citation statements)

References 27 publications

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“…The lack of effect of aging on 5-HT 7 receptor mRNA expression in the hamster hippocampal ventral CA3 region in the current study contrasts with a previous report in rats, in which middleaged and old animals exhibited significantly lower 5-HT 7 receptor mRNA expression than young animals (Kohen et al, 2000). The present results are consistent, however, with an earlier study in rats, which did not observe any age-associated changes in 5-HT 7 receptor mRNA expression in any hippocampal subfield (Yau et al, 1999).…”

Section: Discussioncontrasting

confidence: 99%

“…For example, significant attenuation of serotonergic induction of circadian phase shifts was observed in hamsters by 17-19 months of age (Penev et al, 1995;Duncan et al, 2004), the same age at which a significant reduction of specific 5-HT 7 receptor binding was exhibited in the dorsal raphe nucleus (DRN) (Duncan et al, 1999). Also, age-related memory deficits are exhibited by rodents and humans, and decreased expression of 5-HT 7 receptor mRNA in the ventral CA3 of the hippocampus has been observed in old rats (Kohen et al, 2000) [but see also (Yau et al, 1999)]. …”

Section: Introductionmentioning

confidence: 99%

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Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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Aging affects several processes modulated by the 5-HT 7 receptor subtype, including circadian rhythms, learning and memory, and depression. Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT 7 receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection. To elucidate the mechanisms underlying the aging decrease in 5-HT 7 receptors, we investigated aging modulation of 5-HT 7 receptor mRNA expression in the DRN, brain regions afferent to the DRN, and brain regions regulating circadian rhythms or memory. In situ hybridization for 5-HT 7 receptor mRNA was performed on coronal sections prepared from the brains of young, middle-aged, and old male Syrian hamsters. 5-HT 7 receptor mRNA expression was quantified by densitometry of X-ray film autoradiograms. The results showed that aging did not significantly affect 5-HT 7 receptor mRNA expression in the DRN or most other brain regions examined, with the exception of the cingulate cortex and paraventricular thalamic nucleus. Within the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals, 5-HT 7 receptor mRNA expression was localized in a discrete subregion resembling the calbindin subnucleus previously described. A second experiment using adjacent tissue sections showed that 5-HT 7 receptor mRNA and calbindin mRNAs were concentrated in the same region of the SCN, and as well as in the same region of several other brain structures. The localization of 5-HT 7 receptors and calbindin mRNAs within the same regions suggests that proteins they encode may interact to modulate processes such as circadian timekeeping.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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“…Thus, it is possible that modulation of other nuclear protein factors may interfere with GR signaling even in middle-aged animals. In support of this idea, it is known that homeostatic and synaptic regulators of transcription factor activation show gradual changes across the life span; for example, serum T levels decrease progressively with age in rats (43), hippocampal expression of 5-HT7 receptor mRNA is decreased in middleaged animals (44), and neuronal nitric oxide synthase is elevated in hippocampus by middle age (45). Thus, middle age is marked by changes in numerous neuromodulatory signaling pathways that may indirectly impact on GR DNA binding capacity.…”

Section: Discussionmentioning

confidence: 91%

Decrements in Nuclear Glucocorticoid Receptor (GR) Protein Levels and DNA Binding in Aged Rat Hippocampus

Murphy¹,

Spencer²,

Sipe³

et al. 2002

Endocrinology

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Hippocampal glucocorticoid receptors (GRs) are believed to play a major role in age-related cognitive decline and cellular vulnerability. It has been proposed that these receptors mediate damaging effects of elevated glucocorticoid secretion on cellular function. In the present report we present evidence that intracellular trafficking of the GR is impaired with hippocampal aging, manifest as decreased nuclear translocation and deficient DNA binding. We also present evidence that chaperone proteins responsible for GR nuclear translocation are decreased with hippocampal aging. Age-related nuclear GR decreases are not observed in hypothalamus, indicating regional specificity of trafficking deficits. Aging did not affect nuclear or cytosolic MR levels. These data suggest that GR signaling is diminished, rather than enhanced, during hippocampal aging. Diminished GR signaling capacity may attenuate the beneficial effects of glucocorticoids on hippocampal regulation of memory and stress integration.

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“…Data on other neurotransmitter suggest there are similar age-related changes to those seen in the dopaminergic system (McGeer et al, 1977;Petkov et al, 1988;Suhara et al, 1993;Meltzer et al, 1998;Miguez et al, 1999;Gross-Isseroff et al, 2000;Ishida et al, 2000;Segovia et al, 2001). Studies also provide evidence for both linear (Pirker et al, 2000) and non-linear (Kohen et al, 2000) models to explain these changes. In general, theories of ageing would tend to support non-linear kinetic models (Crevecoeur, 2001), which would mean that the most profound losses occur before middle age.…”

Section: Functional Implicationsmentioning

confidence: 89%