Antidepressants in Alzheimer’s Disease: A Focus on the Role of Mirtazapine

Correia, Ana Salomé; Vale, Nuno

doi:10.3390/ph14090930

Cited by 22 publications

(18 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The three drugs that interact with 5-HT3 receptor (mirtazapine, scopolamine, and lamotrigine), in all the tested concentrations, did not lead to cell damage/toxicity, revealing to be good stress reversers in these concentrations. These observations are in concordance with some of the literature, which reports the potential of these drugs to be used in the therapy of depression [ 26 , 34 , 35 ], as described in the Introduction section. Additionally, HPLC results for these drugs demonstrated that they do not substantially affect 5-HT levels on the extracellular medium, compared to the vehicle, for both cell lines.…”

Section: Discussionsupporting

confidence: 91%

Serotonin Type 3 Receptor Is Potentially Involved in Cellular Stress Induced by Hydrogen Peroxide

Correia

Silva

Oliveira

et al. 2022

Life

View full text Add to dashboard Cite

Depression is a disease with several molecular mechanisms involved, such as problems in the serotonergic pathway. This disease is very complex and prevalent, and thus important to deeply study and aim to overcome high rates of relapse and therapeutic failure. In this study, two cellular lines were used (HT-22 and SH-SY5Y cells) to gain insight about the role of the serotonin type 3 (5-HT3) receptor in cellular stress induced by hydrogen peroxide and/or corticosterone. In research, these compounds are known to mimic the high levels of oxidative stress and dysfunction of the hypothalamus–hypophysis–adrenal axis by the action of glucocorticoids, usually present in depressed individuals. The receptor 5-HT3 is also known to be involved in depression, previously demonstrated in studies that highlight the role of these receptors as promising targets for antidepressant therapy. Indeed, the drugs used in this work (mirtazapine, scopolamine, and lamotrigine) interact with this serotonergic receptor. Thus, by using cell morphology, cell viability (neutral red and MTT), and HPLC assays, this work aimed to understand the role of these drugs in the stress induced by H2O2/corticosterone to HT-22 and SH-SY5Y cell lines. We concluded that the antagonism of the 5-HT3 receptor by these drugs may be important in the attenuation of H2O2-induced oxidative stress to the cells, but not in the corticosterone-induced stress.

show abstract

Section: Discussionsupporting

confidence: 91%

Serotonin Type 3 Receptor Is Potentially Involved in Cellular Stress Induced by Hydrogen Peroxide

Correia

Silva

Oliveira

et al. 2022

Life

View full text Add to dashboard Cite

show abstract

“…Different groups are currently studying antidepressants in AD (Lozupone et al, 2018). Second-generation antidepressants have been associated with a reduced risk of developing AD, but there are still no clear findings demonstrating the ability of these drugs to counteract the progression of this disease (Correia and Vale, 2021). Positive outcomes have been observed by using selective serotonin reuptake inhibitors (SSRIs) (Dafsari and Jessen, 2020).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Activity of Fluoxetine and Vortioxetine in a Non-Transgenic Animal Model of Alzheimer’s Disease

et al. 2021

View full text Add to dashboard Cite

Depression is a risk factor for the development of Alzheimer’s disease (AD). A neurobiological and clinical continuum exists between AD and depression, with neuroinflammation and oxidative stress being involved in both diseases. Second-generation antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are currently investigated as neuroprotective drugs in AD. By employing a non-transgenic AD model, obtained by intracerebroventricular (i.c.v.) injection of amyloid-β (Aβ) oligomers in 2-month-old C57BL/6 mice, we recently demonstrated that the SSRI fluoxetine (FLX) and the multimodal antidepressant vortioxetine (VTX) reversed the depressive-like phenotype and memory deficits induced by Aβ oligomers rescuing the levels of transforming growth factor-β1 (TGF-β1). Aim of our study was to test FLX and VTX for their ability to prevent oxidative stress in the hippocampus of Aβ-injected mice, a brain area strongly affected in both depression and AD. The long-term intraperitoneal (i.p.) administration of FLX (10 mg/kg) or VTX (5 and 10 mg/kg) for 24 days, starting 7 days before Aβ injection, was able to prevent the over-expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (Nox2) induced by Aβ oligomers. Antidepressant pre-treatment was also able to rescue the mRNA expression of glutathione peroxidase 1 (Gpx1) antioxidant enzyme. FLX and VTX also prevented Aβ-induced neurodegeneration in mixed neuronal cultures treated with Aβ oligomers. Our data represent the first evidence that the long-term treatment with the antidepressants FLX or VTX can prevent the oxidative stress phenomena related to the cognitive deficits and depressive-like phenotype observed in a non-transgenic animal model of AD.

show abstract

“…It is prescribed for the treatment of depression symptoms. Depression is also prevalent among AD patients [ 183 ]. According to the literature, mirtazapine improved depression and anxiety, as well as insomnia and weight loss in AD patients [ 184 ].…”

Section: Clinical Trials For Alzheimer’s Disease Based On the Locus C...mentioning

confidence: 99%

The Contribution of the Locus Coeruleus–Noradrenaline System Degeneration during the Progression of Alzheimer’s Disease

Mercan

Heneka

2022

Biology

View full text Add to dashboard Cite

Alzheimer’s disease (AD), which is characterized by extracellular accumulation of amyloid-beta peptide and intracellular aggregation of hyperphosphorylated tau, is the most common form of dementia. Memory loss, cognitive decline and disorientation are the ultimate consequences of neuronal death, synapse loss and neuroinflammation in AD. In general, there are many brain regions affected but neuronal loss in the locus coeruleus (LC) is one of the earliest indicators of neurodegeneration in AD. Since the LC is the main source of noradrenaline (NA) in the brain, degeneration of the LC in AD leads to decreased NA levels, causing increased neuroinflammation, enhanced amyloid and tau burden, decreased phagocytosis and impairment in cognition and long-term synaptic plasticity. In this review, we summarized current findings on the locus coeruleus–noradrenaline system and consequences of its dysfunction which is now recognized as an important contributor to AD progression.

show abstract

Antidepressants in Alzheimer’s Disease: A Focus on the Role of Mirtazapine

Cited by 22 publications

References 109 publications

Serotonin Type 3 Receptor Is Potentially Involved in Cellular Stress Induced by Hydrogen Peroxide

Serotonin Type 3 Receptor Is Potentially Involved in Cellular Stress Induced by Hydrogen Peroxide

Antioxidant Activity of Fluoxetine and Vortioxetine in a Non-Transgenic Animal Model of Alzheimer’s Disease

The Contribution of the Locus Coeruleus–Noradrenaline System Degeneration during the Progression of Alzheimer’s Disease

Contact Info

Product

Resources

About