Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

Cruz, Júlia Niehues da; Magro, Débora Delwing Dal; Lima, Daniela Delwing de; Cruz, José Geraldo Pereira da

doi:10.1590/s2175-97902017000116102

Cited by 6 publications

(1 citation statement)

References 95 publications

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“…Anxiolytic effects of satins—drugs that are used to lower LDL levels—were also discussed in a recent review article [ 123 ]. The mechanisms behind it are assumed due to a modulation of the N -methyl- d -aspartate (NMDA) receptors in the brain, which show a close correlation with anxiety-like behavior.…”

Section: Metabolomics In the Study Of Anxiolytic Effectsmentioning

confidence: 99%

Metabolomic Biomarkers in Anxiety Disorders

Humer

Pieh

Probst

2020

IJMS

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Anxiety disorders range among the most prevalent psychiatric disorders and belong to the leading disorders in the study of the total global burden of disease. Anxiety disorders are complex conditions, with not fully understood etiological mechanisms. Numerous factors, including psychological, genetic, biological, and chemical factors, are thought to be involved in their etiology. Although the diagnosis of anxiety disorders is constantly evolving, diagnostic manuals rely on symptom lists, not on objective biomarkers and treatment effects are small to moderate. The underlying biological factors that drive anxiety disorders may be better suited to serve as biomarkers for guiding personalized medicine, as they are objective and can be measured externally. Therefore, the incorporation of novel biomarkers into current clinical methods might help to generate a classification system for anxiety disorders that can be linked to the underlying dysfunctional pathways. The study of metabolites (metabolomics) in a large-scale manner shows potential for disease diagnosis, for stratification of patients in a heterogeneous patient population, for monitoring therapeutic efficacy and disease progression, and for defining therapeutic targets. All of these are important properties for anxiety disorders, which is a multifactorial condition not involving a single-gene mutation. This review summarizes recent investigations on metabolomics studies in anxiety disorders.

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Section: Metabolomics In the Study Of Anxiolytic Effectsmentioning

confidence: 99%

Metabolomic Biomarkers in Anxiety Disorders

Humer

Pieh

Probst

2020

IJMS

View full text Add to dashboard Cite

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Memantine/Rosuvastatin Therapy Abrogates Cognitive and Hippocampal Injury in an Experimental Model of Alzheimer's Disease in Rats: Role of TGF-β1/Smad Signaling Pathway and Amyloid-β Clearance

Zidan,

El-Mezayen,

Elrewini

et al. 2024

J Neuroimmune Pharmacol

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Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder of complex pathogenesis and multiple interacting signaling pathways where amyloidal-β protein (Aβ) clearance plays a crucial role in cognitive decline. Herein, the current study investigated the possible modulatory effects of memantine/ rosuvastatin therapy on TGF-β1/p-Smad/p21 signaling pathway and their correlation to the blood brain barrier transporters involved in Aβ-clearance and microRNAs as a novel molecular mechanism in AD treatment. AD was induced by a single intracerebroventricular streptozotocin injection (ICV-STZ, 3 mg/kg) in rats and drug therapy was continued for 28 days after AD induction. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, histopathological, molecular and gene expression techniques. The upregulated TGF-β1-signaling in the untreated rats was found to be highly correlated to transporters and microRNAs governing Aβ-efflux; ABCA1/miRNA-26 and LRP1/miRNA-205 expressions, rather than RAGE/miRNA-185 controlling Aβ-influx; an effect that was opposed by the tested drugs and was found to be correlated with the abolished TGF-β1-signaling as well. Combined memantine/rosuvastatin therapy ameliorated the STZ evoked decreases in escape latency and number of crossovers in the Morris water maze test, % spontaneous alternation in the Y-maze test, and discrimination and recognition indices in the object recognition test. The evoked behavioral responses were directly related to the β-amyloid accumulation and the alteration in its clearance. Additionally, drug treatment increased brain glutathione and decreased malondialdehyde levels. These findings were histopathologically confirmed by a marked reduction of gliosis and restoration of neuronal integrity in the CA1 region of the hippocampus of the AD rats. These findings implicated that the memantine/rosuvastatin combination could offer a new therapeutic potential for AD management by abrogating the TGF-β1/p-Smad2/p21 pathway and regulating Aβ-clearance. Graphical Abstract

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