Parkinson's Disease as a Neuroendocrine Disorder of Circadian Function: Dopamine-Melatonin Imbalance and the Visual System in the Genesis and Progression of the Degenerative Process

Willis, Gregory L.

doi:10.1515/revneuro.2008.19.4-5.245

Cited by 86 publications

(98 citation statements)

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“…Indeed, the hypothalamus serves as a crucial centre for the integration and coordination of various brain functions, and as such, it is prone to involvement in several major brain disorders (Saper, 1990;Overeem et al, 2002;Sisk and Foster, 2004;Swaab, 2006;Aziz et al, 2007;Bao et al, 2008;Willis, 2008;Gordon, 2010;Kalsbeek et al, 2010). Precise MRI identification of the gray and white structures of the hypothalamus would also be of great help in developing new research approaches aimed at investigating hypothalamic connectivity (Lemaire et al, 2011) and the functional and/or metabolic changes that occur naturally within the hypothalamus with fluctuating physiological conditions (Baroncini et al, 2010) and/or upon changes to the external environment (Goldstein et al, 2010), as well as in routine clinical examination using 1.5T MRI.…”

Section: Discussionmentioning

confidence: 99%

MRI atlas of the human hypothalamus

et al. 2012

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Gaining new insights into the anatomy of the human hypothalamus is crucial for the development of new treatment strategies involving functional stereotactic neurosurgery. Here, using anatomical comparisons between histology and magnetic resonance images of the human hypothalamus in the coronal plane, we show that discrete gray and white hypothalamic structures are consistently identifiable by MRI. Macroscopic and microscopic images were used to precisely annotate the MRI sequences realized in the coronal plane in twenty healthy volunteers. MRI was performed on a 1.5T scanner, using a protocol including T1-weighted 3D fast field echo, T1-weighted inversionrecovery, turbo spin echo and T2-weighted 2D fast field echo imaging. For each gray matter structure as well as for white matter bundles, the different MRI sequences were analyzed in comparison to each other. The anterior commissure and the fornix were often identifiable, while the mammillothalamic tract was more difficult to spot. Qualitative analyses showed that MRI could also highlight finer structures such as the paraventricular nucleus, the ventromedial nucleus of the hypothalamus and the infundibular (arcuate) nucleus, brain nuclei that play key roles in the regulation of food intake and energy homeostasis. The posterior hypothalamic area, a target for deep brain stimulation in the treatment of cluster headaches, was readily identified, as was the lateral hypothalamic area, which similar to the aforementioned hypothalamic nuclei, could be a putative target for deep brain stimulation in the treatment of obesity. Finally, each of the identified structures was mapped to Montreal Neurological Institute (MNI) space. Please find enclosed the revised version of our manuscript "MRI atlas of the human hypothalamus" which we have modified according to the minor comment made by the reviewer#3.We appreciated the careful and incisive evaluation of our data made by the reviewers throughout the reviewing process. We hope that the manuscript is now in suitable form for publication in Neuroimage.  New insights into the anatomy of the human hypothalamus  Specific 1.5T MRI sequences approach histological resolution within the hypothalamus  White matter bundles within the hypothalamus can be identified using 1.5T MRI  Hypothalamic gray structures can be identified using 1.5T MRI *4. HighlightsWe have revised our manuscript to address the minor point raised by reviewer 3.In the "Data analysis" paragraph of the materials and methods section it now reads: "Structures were identified visually based on our knowledge of specific landmarks obtained from anatomical-histological cross sections and with reference to previously published atlases (Swaab et al., 1993;Koutcherov et al., 2000Koutcherov et al., , 2004Koutcherov et al., 2007;Mai et al., 2008); the landmarks used, such as the optic tract, the floor of the diencephalon, the third ventricle, and the fornix, were readily and reliably identifiable in MR scans." AbstractGaining new insights into the anatomy of the hu...

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Section: Discussionmentioning

confidence: 99%

MRI atlas of the human hypothalamus

et al. 2012

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“…As a result, one in five healthy older individuals reports taking sleep medications regularly (9). In cases of pathological aging, chronobiological disturbance is even more acute: Huntington disease, Parkinson disease, and Alzheimer's disease are all associated with profound alterations in sleeping patterns (10)(11)(12). These effects of aging on circadian rhythms-diminished circadian amplitude, earlier phase, shorter circadian period, and desynchronization of rhythms in peripheral organs-have been observed widely in several species of mammals (7,13,14).…”

mentioning

confidence: 99%

Serum factors in older individuals change cellular clock properties

Pagani

Schmitt²,

Meier³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Human aging is accompanied by dramatic changes in daily sleepwake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cellautonomous circadian clocks functioning in nearly every cell of the body. In fact, human clock properties measured in peripheral cells such as fibroblasts closely mimic those measured physiologically and behaviorally in the same subjects. To understand better the molecular mechanisms by which human aging affects circadian clocks, we characterized the clock properties of fibroblasts cultivated from dermal biopsies of young and older subjects. Fibroblast period length, amplitude, and phase were identical in the two groups even though behavior was not, thereby suggesting that basic clock properties of peripheral cells do not change during aging. Interestingly, measurement of the same cells in the presence of human serum from older donors shortened period length and advanced the phase of cellular circadian rhythms compared with treatment with serum from young subjects, indicating that a circulating factor might alter human chronotype. Further experiments demonstrated that this effect is caused by a thermolabile factor present in serum of older individuals. Thus, even though the molecular machinery of peripheral circadian clocks does not change with age, some age-related circadian dysfunction observed in vivo might be of hormonal origin and therefore might be pharmacologically remediable.chronobiology | peripheral oscillators | human behavior C ircadian clocks possess an endogenous periodicity of about 24 h and play a key role in physiological adaptation to the solar day for all living organisms, from cyanobacteria and fungi (1) to insects (2) and mammals (3). Circadian clocks influence nearly all aspects of physiology and behavior, including sleepwake cycles, body temperature, and the function of many organs (3). During normal aging, clock function is attenuated, with consequences both for health and quality of life. Older individuals have an earlier phase of everyday activity compared with the young (4). Not only is the consolidation of sleep and wake dramatically reduced (5, 6), but overall circadian amplitude of hormones and body temperature are lower (7,8), and many agingassociated sleep-wake pathologies have been reported (9-11). As a result, one in five healthy older individuals reports taking sleep medications regularly (9). In cases of pathological aging, chronobiological disturbance is even more acute: Huntington disease, Parkinson disease, and Alzheimer's disease are all associated with profound alterations in sleeping patterns (10-12). These effects of aging on circadian rhythms-diminished circadian amplitude, earlier phase, shorter circadian period, and desynchronization of rhythms in peripheral organs-have been observed widely in several species of mammals (7,13,14). Paradoxically, however, even though the behavioral phase is earlier in aged humans, m...

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“…Parkinsonian symptoms themselves undergo circadian fluctuations [Willis, 2008]. Patients with PD often experience worsening of symptoms in the afternoon and the evening.…”

Section: Therapeutic Advances In Neurological Disorders 4 (5)mentioning

confidence: 99%

“…A reduction in agitation and psychiatric side effects were also reported in this study. The authors suggested that activation of the circadian system by antagonizing melatonin secretion with bright light has a therapeutic value for treating the symptoms of PD [Willis, 2008].…”

Section: Melatonin As a Therapeutic Agent In Parkinson's Diseasementioning

confidence: 99%

Therapeutic potential of melatonin and its analogs in Parkinson’s disease: focus on sleep and neuroprotection

Srinivasan¹,

Cardinali

Srinivasan

et al. 2011

Ther Adv Neurol Disord

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Sleep disorders constitute major nonmotor features of Parkinson's disease (PD) that have a substantial effect on patients' quality of life and can be related to the progression of the neurodegenerative disease. They can also serve as preclinical markers for PD, as it is the case for rapid eye movement (REM)-associated sleep behavior disorder (RBD). Although the etiology of sleep disorders in PD remains undefined, the assessment of the components of the circadian system, including melatonin secretion, could give therapeutically valuable insight on their pathophysiopathology. Melatonin is a regulator of the sleep/wake cycle and also acts as an effective antioxidant and mitochondrial function protector. A reduction in the expression of melatonin MT 1 and MT 2 receptors has been documented in the substantia nigra of PD patients. The efficacy of melatonin for preventing neuronal cell death and for ameliorating PD symptoms has been demonstrated in animal models of PD employing neurotoxins. A small number of controlled trials indicate that melatonin is useful in treating disturbed sleep in PD, in particular RBD. Whether melatonin and the recently developed melatonergic agents (ramelteon, tasimelteon, agomelatine) have therapeutic potential in PD is also discussed.

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Parkinson's Disease as a Neuroendocrine Disorder of Circadian Function: Dopamine-Melatonin Imbalance and the Visual System in the Genesis and Progression of the Degenerative Process

Cited by 86 publications

References 96 publications

MRI atlas of the human hypothalamus

MRI atlas of the human hypothalamus

Serum factors in older individuals change cellular clock properties

Therapeutic potential of melatonin and its analogs in Parkinson’s disease: focus on sleep and neuroprotection

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