Depressive disorders: Processes leading to neurogeneration and potential novel treatments

Brown, Gregory M.; McIntyre, Roger S.; Rosenblat, Joshua D.; Hardeland, Rüdiger

doi:10.1016/j.pnpbp.2017.04.023

Cited by 36 publications

(41 citation statements)

References 298 publications

(252 reference statements)

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“…This is frequently done in the absence of any awareness of doses required for a specific application, of circadian effects and of changes in the immune system. The possibility that undesired effects occur concerning sleep fragmentation, phase shifting into wrong directions [130], and proinflammatory actions, especially in autoimmune diseases [114], is mostly not perceived prior to such a self-treatment. Moreover, the possibility of reduced melatonergic efficacy by melatonin receptor desensitization is usually not considered, something that has, at least, been observed preclinically [131].…”

Section: Resultsmentioning

confidence: 99%

Untitled

2017

J Geriatr Med Gerontol

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Melatonin is a highly pleiotropic regulator molecule that influences numerous functions in many cell types. Its actions comprise direct and circadian oscillator-mediated effects. The levels of circulating melatonin typically decline in the course of aging. Additionally,various aging-associated diseases further decrease melatonin concentrations. With regard to its remarkably broad spectrum of actions, control mechanisms upstream and downstream of melatonin should be investigated much more in detail with regard to the contribution of epigenetic modulation. The importance of epigenetic alterations has already become evident in the fields of both gerontology and chronobiology. Therefore, it seems necessary to fill the gaps concerning corresponding processes related to melatonin, especially under the aspects of physiologic malfunctions because of aging-associated decreases of melatonin. This review outlines the findings on melatonin's epigenetic actions, as obtained to date, and sets these results in correspondence to general knowledge and many specific findings concerning circadian rhythms. These considerations focus on DNA methylation and erasure of 5-methylcytosine, on histone modification, in particular, acetylation/deacetylation and methylation/demethylation, and on the manifold roles of noncoding RNAs, especially microRNAs. With regard to melatonin's spectrum of actions in the gerontological context, emphasis is given to its contribution to circadian oscillation amplitudes, to anti-inflammatory actions and to antioxidative protection.

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Section: Resultsmentioning

confidence: 99%

Untitled

2017

J Geriatr Med Gerontol

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“…Details concerning the relationship between oxidative/nitrosative stress, inflammation and neurodegeneration have been outlined and reviewed elsewhere [28][29][30] . Numerous other findings that have been repeatedly reviewed, meta-analyzed or studied on a broad scale have shown that sleep loss can be associated with depressive disorders 18,19,[31][32][33][34][35] and neurodegeneration 4,[36][37][38] . Although the causality has often remained unclear, inflammatory processes seem to be frequently involved in the initiation of these pathologies.…”

Section: Consequences Of Sleep Disturbancesmentioning

confidence: 99%

“…Sleep disturbances can have different causes, but they are often related to changes in the circadian system. In this context, it is necessary to distinguish between deviations because of gene variants concerning components of the cellular oscillator machinery and age-associated changes that may result from neurodegeneration, epigenetic dysregulation or decreased expression of amplitude-enhancing factors such as sirtuin 1 (SIRT1) or melatonin 4,28 . Moreover, melatonin is also a sleep-promoting agent, especially in terms of initiating sleep onset 41,42 .…”

Section: Consequences Of Sleep Disturbancesmentioning

confidence: 99%

“…This was for a while mainly seen in the context of neurotransmitter availability in relevant brain structures and, according to this context, actions of antidepressants were interpreted and developed. The suspicion that neurodegeneration may play a crucial role is not entirely new, but has gained increasing attention mainly during the last years [1][2][3][4][5][6] . In the beginning, this seemed more likely in cases in which patients exhibited socially unacceptable behavior or signs of dementia, [7][8][9][10] but was less considered in exclusively depressive disorders, a view that is actually changing 2,4 .…”

Section: Introductionmentioning

confidence: 99%

“…The suspicion that neurodegeneration may play a crucial role is not entirely new, but has gained increasing attention mainly during the last years [1][2][3][4][5][6] . In the beginning, this seemed more likely in cases in which patients exhibited socially unacceptable behavior or signs of dementia, [7][8][9][10] but was less considered in exclusively depressive disorders, a view that is actually changing 2,4 . On the one hand, reduced neurotransmitter concentrations in the synaptic cleft may already be associated with the initiation of neurodegenerative processes, as judged from the influence of other synaptopathic changes, 10,11 and from the fact that classic antidepressants can also display neuroprotective properties 12 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Underrated Circadian System and Its Contribution to Neurodegeneration in Mood Disorders

Hardeland¹

2018

J Mental Health & Clin Psychology

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In the traditional view of mood disorders, the circadian system has been insufficiently considered. However, polymorphisms of circadian oscillator genes in bipolar disorder, seasonal affective disorder, and subforms of major depressive disorder as well as demonstrable deviations in overt circadian rhythms indicate a role of the circadian system in these pathologies. Circadian malfunction affects sleep, and sleep deprivation can initiate proinflammatory responses. Being parts of the circadian system, melatonin and sirtuin 1 deserve particular attention. Either of them displays neuroprotective, antiinflammatory, and circadian amplitude-enhancing properties, which are of relevance to neurodegeneration that is observed in a number of depressive patients. Notably, both circulating melatonin levels as well as sirtuin 1 expression decline by age. In the gerontological context, melatonin upregulates sirtuin 1, which mediates some of melatonin's actions. Correction of a deviating circadian system seems to be of value regarding causes that contribute to depressive symptoms.

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Time‐restricted feeding prevents depressive‐like and anxiety‐like behaviors in male rats exposed to an experimental model of shift‐work

Guerrero‐Vargas¹,

Zárate‐Mozo²,

Guzmán-Ruiz

et al. 2020

J of Neuroscience Research

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Individuals who regularly shift their sleep timing, like night and/or shift-workers suffer from circadian desynchrony and are at risk of developing cardiometabolic diseases and cancer. Also, shift-work is are suggested to be a risk factor for the development of mood disorders such as the burn out syndrome, anxiety, and depression. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental health effects associated with circadian disruption. Here, we explored whether adult male Wistar rats exposed to an experimental model of shift-work (W-AL) developed depressive and/or anxiety-like behaviors and whether this was associated with neuroinflammation in brain areas involved with mood regulation. We also tested whether time-restricted feeding (TRF) to the active phase could ameliorate circadian disruption and therefore would prevent depressive and anxiety-like behaviors as well as neuroinflammation. In male Wistar rats, W-AL induced depressive-like behavior characterized by hypoactivity and anhedonia and induced increased anxiety-like behavior in the open field test. This was associated with increased number of glial fibrillary acidic protein and IBA-1-positive cells in the prefrontal cortex and basolateral amygdala. Moreover W-AL caused morphological changes in the microglia in the CA3 area of the hippocampus indicating microglial activation. Importantly, TRF prevented behavioral changes and decreased neuroinflammation markers in the brain. Present results add up evidence about the importance that TRF in synchrony with the light-dark cycle can prevent neuroinflammation leading to healthy mood states in spite of circadian disruptive conditions.

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Depressive disorders: Processes leading to neurogeneration and potential novel treatments

Cited by 36 publications

References 298 publications

Untitled

Untitled

The Underrated Circadian System and Its Contribution to Neurodegeneration in Mood Disorders

Time‐restricted feeding prevents depressive‐like and anxiety‐like behaviors in male rats exposed to an experimental model of shift‐work

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