Mathematical analysis of the role of pituitary-adrenal interactions in ultradian rhythms of the HPA axis

Malek, Hamed; Ebadzadeh, Mohammad Mehdi; Safabakhsh, Reza; Razavi, Alireza

doi:10.1016/j.compbiomed.2021.104580

Cited by 3 publications

(4 citation statements)

References 15 publications

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“…It is also consolidated and confined by the circadian signal, as are the behavioural ultradian rhythms superimposed upon the circadian rhythm. These characteristics of high period flexibility sustained and subject to circadian regulation parallel other locally sustained ultradian rhythms in various biological contexts, such as the pituitary-adrenal regulation and central nucleus mechanisms impacting immune responses, metabolism, and development [ 4 , 45 , 80 ]. These distinct mechanisms share a common structural feature in utilizing negative auto-regulation without additional stabilizing loops commonly seen in circadian clocks.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with circadian DA rhythm, the ultradian DA rhythm relates more to local mechanisms regulating DA release and reuptake and is less affected by the availability of DA cellular molecules [ 37 ]. A previous model of the hypothalamic-pituitary-adrenal axis [ 45 ] demonstrated the capacity of individual neural networks to autonomously produce ultradian rhythms through local processes involving negative feedback loops and respond to external inputs from the global circadian rhythm. It is thus possible that the ultradian rhythm observed in striatal DA tone is generated through local synaptic processes while modulated by the circadian system.…”

Section: Introductionmentioning

confidence: 99%

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A mathematical model for the role of dopamine-D2 self-regulation in the production of ultradian rhythms

Zhang,

Ralph,

Stinchcombe

2024

PLoS Comput Biol

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Many self-motivated and goal-directed behaviours display highly flexible, approximately 4 hour ultradian (shorter than a day) oscillations. Despite lacking direct correspondence to physical cycles in the environment, these ultradian rhythms may be involved in optimizing functional interactions with the environment and reflect intrinsic neural dynamics. Current evidence supports a role of mesostriatal dopamine (DA) in the expression and propagation of ultradian rhythmicity, however, the biochemical processes underpinning these oscillations remain to be identified. Here, we use a mathematical model to investigate D2 autoreceptor-dependent DA self-regulation as the source of ultradian behavioural rhythms. DA concentration at the midbrain-striatal synapses is governed through a dual-negative feedback-loop structure, which naturally gives rise to rhythmicity. This model shows the propensity of striatal DA to produce an ultradian oscillation characterized by a flexible period that is highly sensitive to parameter variations. Circadian (approximately 24 hour) regulation consolidates the ultradian oscillations and alters their response to the phase-dependent, rapid-resetting effect of a transient excitatory stimulus. Within a circadian framework, the ultradian rhythm orchestrates behavioural activity and enhances responsiveness to an external stimulus. This suggests a role for the circadian-ultradian timekeeping hierarchy in governing organized behaviour and shaping daily experience through coordinating the motivation to engage in recurring, albeit not highly predictable events, such as social interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A mathematical model for the role of dopamine-D2 self-regulation in the production of ultradian rhythms

Zhang,

Ralph,

Stinchcombe

2024

PLoS Comput Biol

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“…Jones and coworkers demonstrated the role of circadian neurons in the paraventricular nucleus in entraining and sustaining daily rhythms in glucocorticoids [47]. Malek and coworkers, using a mathematical analysis of the role of pituitary-adrenal interactions in ultradian rhythms of the hypothalamic-pituitary-adrenal (HPA) axis, demonstrated the persistence of ultradian adrenocorticotropic hormone (ACTH) and cortisol rhythms in absence of corticotropin-releasing hormone (CRH) stimulation [48]. ACTH and cortisol show circadian and ultradian rhythms with overlapping phases, with the zenith in the morning and the nadir in late evening/night, suggesting a driving ACTH role in these rhythmic variations [6,7,[47][48][49] (Figure 1).…”

Section: Chrono-organization Of the Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

“…Malek and coworkers, using a mathematical analysis of the role of pituitary-adrenal interactions in ultradian rhythms of the hypothalamic-pituitary-adrenal (HPA) axis, demonstrated the persistence of ultradian adrenocorticotropic hormone (ACTH) and cortisol rhythms in absence of corticotropin-releasing hormone (CRH) stimulation [48]. ACTH and cortisol show circadian and ultradian rhythms with overlapping phases, with the zenith in the morning and the nadir in late evening/night, suggesting a driving ACTH role in these rhythmic variations [6,7,[47][48][49] (Figure 1). Light is the most important entraining agent of these rhythms: in fact, the lack of light stimulus in totally blind subjects induces an increase in melatonin secretion, and circadian rhythm disorders and complex hormonal alterations in prepubertal, adult and elderly blind subjects [50][51][52][53][54].…”

Section: Chrono-organization Of the Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects

Mercadante,

Bellastella

2024

Life

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This review was aimed at collecting the knowledge on the pathophysiological and clinical aspects of endocrine rhythms and their implications in clinical practice, derived from the published literature and from some personal experiences on this topic. We chose to review, according to the PRISMA guidelines, the results of original and observational studies, reviews, meta-analyses and case reports published up to March 2024. Thus, after summarizing the general aspects of biological rhythms, we will describe the characteristics of several endocrine rhythms and the consequences of their disruption, paying particular attention to the implications in clinical practice. Rhythmic endocrine secretions, like other physiological rhythms, are genetically determined and regulated by a central hypothalamic CLOCK located in the suprachiasmatic nucleus, which links the timing of the rhythms to independent clocks, in a hierarchical organization for the regulation of physiology and behavior. However, some environmental factors, such as daily cycles of light/darkness, sleep/wake, and timing of food intake, may influence the rhythm characteristics. Endocrine rhythms are involved in important physiological processes and their disruption may cause several disorders and also cancer. Thus, it is very important to prevent disruptions of endocrine rhythms and to restore a previously altered rhythm by an early corrective chronotherapy.

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Dynamics of a pituitary–adrenal model with distributed time delays

Kaslik,

Matei,

Neamţu

2025

Communications in Nonlinear Science and Numerical Simulation

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Mathematical analysis of the role of pituitary-adrenal interactions in ultradian rhythms of the HPA axis

Cited by 3 publications

References 15 publications

A mathematical model for the role of dopamine-D2 self-regulation in the production of ultradian rhythms

A mathematical model for the role of dopamine-D2 self-regulation in the production of ultradian rhythms

Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects

Dynamics of a pituitary–adrenal model with distributed time delays

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