Late-life Depression and Alzheimer Disease: A Potential Synergy of the Underlying Mechanisms

Leszek, Jerzy; Trypka, Elżbieta; Koutsouraki, Euphrosyni; Michmizos, Dimitrios; Yarla, Nagendra Sastry; Tarasov, Vadim V.; Ashraf, Ghulam Md; Aliev, Gjumrakch

doi:10.2174/0929867323666160902152829

Cited by 10 publications

(6 citation statements)

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“…At present, considerable progress has been made in understanding the pathophysiology of severe depression, but there is still no model or mechanism that can be satisfactorily explained from all aspects [8]. In recent years, with the rapid development of neurophysiology and neuropathology, people gradually realize that depression is a complex physiological dysfunction caused by different reasons [36][37][38]. There are many hypotheses about the pathogenesis of depression, and neurotrophic factor deficiency is one of the most important hypotheses [39,40].…”

Section: Biomed Research Internationalmentioning

confidence: 99%

Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Yan

et al. 2020

BioMed Research International

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Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

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Section: Biomed Research Internationalmentioning

confidence: 99%

Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Yan

et al. 2020

BioMed Research International

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“…An estrogen-RAS axis seems to exist, where estrogen has increased levels of Ang 1-7 and NEP and decreased levels of Ang II in hypertensive rat models (Brosnihan et al 1997;O'Hagan et al 2012;Pendergrass et al 2008). Association of depression and cognitive impairment has been proved especially in the elderly suggesting that depression represents a prodromal clinical phase of the neurodegenerative changes that occur in AD rather than being just a risk factor (Leszek et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Perindopril ameliorates experimental Alzheimer’s disease progression: role of amyloid β degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling

et al. 2020

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Accumulating evidence indicates that over-stimulation of angiotensin-converting enzyme 1 (ACE1) activity is associated with β-amyloid (Aβ) and phosphorylated tau (p-tau)-induced apoptosis, oxido-nitrosative neuroinflammatory stress and neurodegeneration in Alzheimer's disease (AD). Alternatively, activation of the ACE2, the metalloprotease neprilysin (Neutral Endopeptidase; NEP) and the insulin-degrading enzyme (IDE) could oppose the effects of ACE1 activation. We aim to investigate the relationship between ACE1/ACE2/NEP/IDE and amyloidogenic/hyperlipidemic-lipid raft signaling in hyperlipidemic AD model. Induction of AD was performed in ovariectomized female rats with high-fat high fructose diet (HFFD) feeding after 4 weeks following d-galactose injection (150 mg/kg). The brain-penetrating ACE1 inhibitor perindopril (0.5 mg/kg/day, p.o.) was administered on a daily basis for 30 days. Perindopril significantly decreased hippocampal expression of ACE1 and increased expression of ACE2, NEP and IDE. Perindopril markedly decreased Aβ 1-42 , improved lipid profile and ameliorated the lipid raft protein markers caveolin1 (CAV1) and flotillin 1 (FLOT1). This was accompanied by decreased expression of p-tau and enhancement of cholinergic neurotransmission, coupled with decreased oxido-nitrosative neuroinflammatory stress, enhancement of blood-brain barrier (BBB) functioning and lower expression of the apoptotic markers glial fibrillary acidic protein (GFAP), Bax and β-tubulin. In addition, perindopril ameliorated histopathological damage and improved learning, cognitive and recognition impairment as well as depressive behavior in Morris water maze, Y maze, novel object recognition and forced swimming tests, respectively. Conclusively, perindopril could improve cognitive defects in AD rats, at least through activation of ACE2/NEP/IDE and inhibition of ACE1 and subsequent modulation of amyloidogenic/hyperlipidemic-lipid raft signaling and oxido-nitrosative stress.

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“…ACTH then triggers the release of glucocorticoids (GCs) from the adrenal glands into the bloodstream. Physiological adaptations in response to stress are made possible by GCs, as well as epinephrine and norepinephrine from the sympathetic nervous system ( 69 ). However, in both AD and LLD patients, the HPA axis is dysregulated, leading to impaired negative feedback and increased GCs levels in the brain ( 70 , 71 ).…”

Section: Discussionmentioning

confidence: 99%

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer’s disease: a comparative study

Chu,

Pan,

Ren

et al. 2023

Front. Psychiatry

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ObjectivesAlzheimer’s disease (AD) and late-life depression (LLD) frequently exhibit executive function deficits (EFD) and medial temporal lobe atrophy (MTA) as shared characteristics. The objective of this research was to examine the utility of the Trail Making Test (TMT) and the MTA scale in distinguishing between LLD and AD.MethodsA study of 100 patients, 50 with AD and 50 with LLD, was conducted using a cross-sectional design. The individuals were subjected to clinical evaluations to assess their level of depression and overall cognitive abilities, which included the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). We evaluated executive function deficits (EFD) through the use of the TMT, which includes both TMT-A and TMT-B. MTA was measured using magnetic resonance imaging. To evaluate the ability of TMT and MTA scale to distinguish between the two groups, a receiver operating characteristic (ROC) curve was utilized. To investigate the connections between MTA and neuropsychological measures, a correlation analysis was performed.ResultsAD patients exhibited notably reduced MMSE, MoCA, and GDS scores, as well as an increased MTA total scores, time spent on TMT-A, and TMT-B compared to LLD patients (p < 0.05). TMT-A and TMT-B both exhibited excellent discriminatory power between AD and LLD, achieving area under curve (AUC) values of 92.2 and 94.2%, respectively. In AD patients, there was a negative correlation between MMSE and MoCA scores and MTA scores, while in LLD patients, there was a positive correlation between time spent on TMT-A and GDS scores and MTA scores.ConclusionAD patients experience more severe EFD and MTA than LLD patients. The differential diagnosis of AD and LLD can be aided by the useful tool known as TMT. It is important to acknowledge that TMT is capable of capturing only a fraction of the executive function, thus necessitating a cautious interpretation of research findings.

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Late-life Depression and Alzheimer Disease: A Potential Synergy of the Underlying Mechanisms

Cited by 10 publications

References 0 publications

Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Perindopril ameliorates experimental Alzheimer’s disease progression: role of amyloid β degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer’s disease: a comparative study

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