Prospecting for a quinoline containing selenium for comorbidities depression and memory impairment induced by restriction stress in mice

Rationale Depression is often associated with memory impairment, a clinical feature of Alzheimer’s disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. Objective...

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Bibliographic Details
Published in:Psychopharmacology 2022, Vol.239 (1), p.59-81
Main Authors: de Oliveira, Renata L., Voss, Guilherme T., da C. Rodrigues, Karline, Pinz, Mikaela P., Biondi, Julia V., Becker, Nicole P., Blodorn, Eduardo, Domingues, William B., Larroza, Allya, Campos, Vinícius F., Alves, Diego, Wilhelm, Ethel A., Luchese, Cristiane
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Acetylcholinesterase
Acetylcholinesterase - metabolism
AKT protein
AKT2 protein
Alzheimer's disease
Amine oxidase (flavin-containing)
Animal memory
Animals
Antidepressants
Biomedical and Life Sciences
Biomedicine
Central nervous system
Central nervous system agents
Comorbidity
Corticosterone
Depression - drug therapy
Depression, Mental
Donepezil
Drug therapy
Gene expression
Hippocampus - metabolism
Hypothalamic-pituitary-adrenal axis
Hypothalamo-Hypophyseal System - metabolism
Inflammation
Interleukin 18
Kinases
Male
Memory
Memory, Disorders of
Mental depression
Mice
Neurodegenerative diseases
Neuroinflammatory Diseases
Neurosciences
NF-κB protein
Original Investigation
Oxidative Stress
Paroxetine
Pharmacology, Experimental
Pharmacology/Toxicology
Pituitary-Adrenal System - metabolism
Prefrontal cortex
Psychiatry
Quinoline
Quinolines - pharmacology
Selenium
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Summary:Rationale Depression is often associated with memory impairment, a clinical feature of Alzheimer’s disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. Objectives The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. Methods ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1β, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. Results 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. Conclusions These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-021-06039-8