Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque

Downs, Jodi L.; Dunn, Michael R.; Borók, Erzsébet; Shanabrough, Marya; Horváth, Tamas L.; Kohama, Steven G.; Urbanski, Henryk F.

doi:10.1016/j.neurobiolaging.2006.05.025

Cited by 67 publications

(65 citation statements)

References 34 publications

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“…An example of this self-sustained rhythmicity is illustrated in figure 1. The motor activity data depicted in figure 1a were obtained from an adult rhesus macaque using an Actiwatch, and emphasize the highly entrained diurnal pattern of activity that occurs under fixed 12L:12D photoperiods [33,34,35,36]. In addition, the data show how the activity rhythm becomes free-running, with slight phase advancement, when the animal is exposed to continuous dim illumination (30 lx).…”

Section: Circadian Hormone Rhythms Help With Adaptation To Daily Envimentioning

confidence: 84%

Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

Urbanski¹

2011

Neuroendocrinology

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Hormones play a major role in regulating behavior and physiology, and their efficacy is often dependent on the temporal pattern in which they are secreted. Significant insights into the mechanisms underlying rhythmic hormone secretion have been gained from transgenic rodent models, suggesting that many of the body’s rhythmic functions are regulated by a coordinated network of central and peripheral circadian pacemakers. Some neuroendocrine rhythms are driven by transcriptional-posttranslational feedback circuits comprising ‘core clock genes’, while others represent a cyclic cascade of neuroendocrine events. This review focuses on recent data from the rhesus macaque, a non-human primate model with high clinical translation potential. With primary emphasis on adrenal and gonadal steroids, it illustrates the rhythmic nature of hormone secretion, and discusses the impact that fluctuating hormone levels have on the accuracy of clinical diagnoses and on the design of effective hormone replacement therapies in the elderly. In addition, this minireview raises awareness of the rhythmic expression patterns shown by many genes, and discusses how this could impact interpretation of data obtained from gene profiling studies, especially from nocturnal rodents.

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Section: Circadian Hormone Rhythms Help With Adaptation To Daily Envimentioning

confidence: 84%

Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

Urbanski¹

2011

Neuroendocrinology

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“…In ageing rhesus monkeys, reduced OxB immunoreactivity was observed in the LC while there was no decline in the hypothalamus [25]. The lack of changes in the hypothalamus in Downs et al [25] may be due to the age range examined since relatively small (10 %) reduction in Ox immunoreactivity occurs over this age range [45]. A possible explanation for the difference in decreased immunoreactivity could be that SIDS infants have a large release of Ox from axon fibres prior to death, which is not recovered due to inhibition of PPO synthesis by hypoxia or lack of vesicle translocation.…”

Section: Mechanisms Of Decreased Ox Immunoreactivitymentioning

confidence: 87%

“…A similar immunoreactive expression pattern (where fibres show a greater loss of immunoreactivity then Ox neurons) has been observed during ageing; Sawai et al [89] reported that there was a difference between the number of Ox staining neurons (decreased by 10-25 %) and the area of fibre immunoreactivity of this staining (decreased by 60-80 %) in ageing mice. In ageing rhesus monkeys, reduced OxB immunoreactivity was observed in the LC while there was no decline in the hypothalamus [25]. The lack of changes in the hypothalamus in Downs et al [25] may be due to the age range examined since relatively small (10 %) reduction in Ox immunoreactivity occurs over this age range [45].…”

Section: Mechanisms Of Decreased Ox Immunoreactivitymentioning

confidence: 89%

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

et al. 2015

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Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin. This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died from SIDS compared to age-matched non-SIDS infants. The percentage of orexin immunoreactive neurons and the total number of neurons were quantified in the dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal hypothalamus. In the pons, the area of orexin immunoreactive fibres were quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to 21 % within each of the three levels of the hypothalamus compared to non-SIDS (p ≤ 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC, LDT, DTg and Pn (p ≤ 0.025). No correlations were found between the decreased orexin immunoreactivity and previously identified risk factors for SIDS, including prone sleeping position and cigarette smoke exposure. This finding of reduced orexin immunoreactivity in SIDS infants may be associated with sleep dysfunction and impaired arousal.

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“…Another possibility is that animals with WM deficits have insufficient release of norepinephrine in the PFC. A recent study has shown that excitatory orexin innervation is decreased along with a significant decrease in tyrosine hydroxylase mRNA in the locus coeruleus of aged macaques (Downs et al, 2006), suggesting that there could be decrease in the release of norepinephrine in the aged PFC. Thus, it may be possible that aged animals with PFC deficits benefit from clenbuterol treatment due to low norepinephrine release that does not activate enough β2 adrenoceptors.…”

Section: Discussionmentioning

confidence: 99%

β2 adrenergic agonist, clenbuterol, enhances working memory performance in aging animals

Ramos

Colgan

Nou

et al. 2008

Neurobiology of Aging

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Previous studies using a mixed β1 and β2 adrenergic antagonist, propanolol, have indicated that β adrenoceptors have little effect on the cognitive functioning of the prefrontal cortex. However, recent studies have suggested that endogenous stimulation of β1 adrenoceptors impairs working memory in both rats and monkeys. Since propanolol has no effect on cognition, we hypothesized that activation of β2 adrenoceptors might improve performance in a working memory task. We tested this hypothesis by observing the effects of the β2 agonist, clenbuterol, on spatial working memory performance. Clenbuterol was either infused directly into the prefrontal cortex (rats) or administered systemically (monkeys). Results demonstrated that clenbuterol improved performance in many young and aged rats and monkeys who performed poorly under control conditions. Actions at β2 adrenoceptors were confirmed by challenging the clenbuterol response with the β2 adrenergic antagonist, ICI 118,551. The effects of clenbuterol were not universal and depended on the cognitive status of the animal: the drug moderately improved only a subset of animals with working memory impairment.

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Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque

Cited by 67 publications

References 34 publications

Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

β2 adrenergic agonist, clenbuterol, enhances working memory performance in aging animals

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