Depression—an underrecognized target for prevention of dementia in Alzheimer’s disease

Dafsari, Forugh S.; Jessen, Frank

doi:10.1038/s41398-020-0839-1

Cited by 179 publications

(175 citation statements)

References 119 publications

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“…In brief, neurotransmitter imbalance and hypothalamic-pituitary-adrenal axis dysregulation in depression and mental illness may cause increased amyloid precursor protein expression, decreased brain-derived neurotrophic factor expression, hippocampal cell injury and death, synaptogenesis, neurogenesis, and synaptic plasticity etc. [34,35]. This in turn would lead to amyloid deposition, tau hyperphosphorylation and aggregation, and neurodegeneration which are the pathological hallmark of dementia [34,35].…”

Section: Discussionmentioning

confidence: 99%

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The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia

Phyo

González‐Chica

Stocks

et al. 2021

JAD

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Background: Health-related quality of life (HRQoL) has been shown to predict adverse health outcome in the general population. Objective: We examined the cross-sectional association between HRQoL and cognitive performance at baseline. Next, we explored whether baseline HRQoL predicted 5-year incident cognitive decline and dementia and whether there were gender differences. Methods: 19,106 community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, aged 65–98 years, free of major cognitive impairments, and completed the HRQoL 12-item short-form (SF-12) at baseline (2010–2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were calculated. The cognitive tests were assessed at baseline, year 1, 3, 5, and 7 or close-out visit. Cognitive decline was defined as > 1.5 SD drop from baseline on any of the cognitive tests. Dementia was adjudicated according to DSM-IV criteria. Linear and Cox proportional-hazards regressions were used to examine the cross-sectional and longitudinal associations respectively. Results: At baseline, higher PCS and MCS were associated with better cognition. Over a median 4.7-year follow-up, higher MCS was associated with a reduced risk of cognitive decline and dementia (12% and 15% respectively, per 10-unit increase) and a 10-unit higher PCS was associated with a 6% decreased risk of cognitive decline. PCS did not predict dementia incidence. Findings were not different by gender. Conclusion: Our study found that higher HRQoL, in particular MCS, predicted a reduced risk of cognitive decline and dementia over time in community-dwelling older people.

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Section: Discussionmentioning

confidence: 99%

“…[34,35]. This in turn would lead to amyloid deposition, tau hyperphosphorylation and aggregation, and neurodegeneration which are the pathological hallmark of dementia [34,35]. In addition, sleep problems are a common symptom in depression [36], and may be associated with worse MCS.…”

Section: Discussionmentioning

confidence: 99%

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia

Phyo

González‐Chica

Stocks

et al. 2021

JAD

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“…Fluoxetine is an antidepressant drug that when applied at the clinical dose promotes an increase in serotonin levels due to the inhibition of the reuptake of this neurotransmitter into the synaptic cleft. This blockage causes an increase in serotonin, but at a sub-effective dose this would not be enough to generate FST effect ( Dafsari and Jessen, 2020 ; Han et al., 2019 ; Jeong et al., 2019 ; Melo et al., 2015 ; Nakai et al., 2017 ). In association with the RO and considering that this substance could also interfere with serotonergic neurotransmission, we can thus justify the effect observed in the association of the two substances.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission

Maia

Andrade

Filgueiras

et al. 2021

Heliyon

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Rose oxide (RO) is a monoterpene found in rose oil fragrances. This monoterpene has been reported to possess anti-inflammatory activity, however, little is known regarding its pharmacological activity. The present study was carried out to evaluate its antidepressant action and possible mechanisms of action. Analysis of ADMET pharmacokinetic properties (absorption, distribution, metabolism, excretion and toxicity) of rose oxide was performed by computational prediction analysis. Behavioral tests were performed to assess the interaction between rose oxide and the central nervous system and antidepressant effect that includes: forced swim test (FST), tail suspension test (TST), open field test (OFT) and rota-rod test. The results of pharmacokinetic and toxicological properties indicate that rose oxide could be used orally, since it has good intestinal absorption as well as pharmacological and toxicological properties that can be similar to pharmacological compounds (regular hepatic metabolism and low toxicity). Treatment with 50 mg/kg of rose oxide was able to decrease the immobility time of animals not affected by FST and TST and was not able to alter the motor activity of the OFT and rota-rod test, suggesting modulation and antidepressant activity. Docking data suggest that rose oxide can bind to receptors in the serotonergic pathway. The results described here suggest that rose oxide has antidepressant activity, modulating the serotonergic pathway.

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“…We performed a series of astrocyte functional evaluations, immunohistochemistry (IHC), behavioral assessments, and RNA sequencing (RNA-seq) in the mouse prefrontal cortex (PFC) of mice injected with a single peripheral dose of lipopolysaccharide (LPS) to mimic antigen presentation and neuroinflammation (Zamanian et al, 2012;Bhattacharya et al, 2018). As the main integrator of the decision making circuits of the limbic system, the PFC becomes dysfunctional in both psychiatric and dementia-related disorders and when symptoms such as anhedonia are observed (Russo and Nestler, 2013;Elahi and Miller, 2017;Dafsari and Jessen, 2020;Haber et al, 2020). Astrocyte specific and whole tissue RNA-seq was performed during the development and recovery of anhedonia with the goal of identifying molecular changes within astrocytes in an unbiased way (Srinivasan et al, 2016;Chai et al, 2017;Yu et al, 2018;Yu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Molecular and functional properties of PFC astrocytes during neuroinflammation-induced anhedonia

Díaz-Castro

Bernstein

Coppola

et al. 2020

Preprint

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Astrocytes are widely implicated in CNS diseases, but their contributions to disease related phenotypes remain incompletely explored. Anhedonia accompanies several neurological and psychiatric diseases, including major depressive disorder (MDD) and Alzheimer’s disease (AD), both of which are associated with neuroinflammation. In order to explore how neuroinflammation affects astrocytes, we assessed medial prefrontal cortex (PFC) and visual cortex (VCX) astrocytic gene expression using a neuroinflammation mouse model that displayed anhedonia as a phenotype. In this model, anhedonia was reversed by the fast acting antidepressant ketamine. Astrocyte specific gene expression alterations included those related to immune cell signaling, intracellular Ca2+ signaling, cholesterol biosynthesis, and metabolic pathways. Such changes peaked when anhedonia was greatest, and reversed to normal when anhedonia subsided. However, region-specific molecular identities between PFC and VCX astrocytes were maintained throughout, implying that astrocyte identities do not converge during neuroinflammation. We also mapped anhedonia-related astrocyte and bulk tissue gene expression changes onto published PFC single cell RNA sequencing data, and compared them to MDD and AD post-mortem human tissue samples to identify shared mechanisms. Finally, we assessed how neuroinflammation affected mPFC neuronal properties and detected no alterations at a time point when there was strong astrocyte reactivity. Our data show that neuroinflammation can cause significant and reversible changes in astrocyte gene expression and mouse behaviour without obvious neurotoxicity or loss of essential homeostatic functions. Furthermore, gene expression signatures accompanying neuroinflammation reveal pathways shared with MDD and AD, which display neuroinflammation as a comorbidity in humans.Significance statementAstrocytes are widely implicated in brain diseases, but their contributions to disease-related phenotypes remain incompletely explored. To make inroads into this problem, we assessed medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte gene expression using a peripherally induced neuroinflammation mouse model that produced anhedonia – a phenotype associated with several brain disorders. Neuroinflammation caused reversible changes in mouse behaviour and astrocyte-specific gene expression changes, some of which were related to human post mortem data for major depressive disorder (MDD) and Alzheimer’s disease (AD), but without any clear evidence of neurotoxicity in PFC of mice. The astrocyte molecular alterations accompanying neuroinflammation-induced anhedonia will be informative to explore diverse brain disorders and the effects of neuroinflammation on the CNS more broadly.

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Depression—an underrecognized target for prevention of dementia in Alzheimer’s disease

Cited by 179 publications

References 119 publications

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission

Molecular and functional properties of PFC astrocytes during neuroinflammation-induced anhedonia

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