Molecular Biological Aspects of Depressive Disorders: A Modern View

Ushakova, Valeria; Morozova, Аnna; Reznik, A. M.; Kostyuk, Georgiy; Чехонин, В. П.

doi:10.1134/s0026893320050118

Cited by 10 publications

(7 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The observed changes in noradrenaline and dopamine metabolism could be mediated by the activation of tyrosine hydroxylase, since this enzyme facilitates the conversion of l -tyrosine into the dopamine precursor l -3,4-dihydroxyphenylalanine, and an increase in its activity may lead to elevated monoamine levels . The role of noradrenergic and dopaminergic system in the pathogenesis of major depressive disorder has been widely demonstrated in the literature. − Moreover, a class of antidepressants called serotonin–norepinephrine reuptake inhibitors (SNRIs) are precisely aimed at modulating noradrenaline . We suppose that the identified neurochemical changes may also contribute to the antidepressant-like effects of vindeburnol that we observed in behavioral assessments.…”

Section: Resultsmentioning

confidence: 99%

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Zubkov,

Riabova,

Zorkina

et al. 2024

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Vindeburnol (VIND, RU24722, BC19), a synthetic molecule derived from the eburnamine-vincamine alkaloid group, has many neuropsychopharmacological effects, but its antidepressant-like effects are poorly understood and have only been described in a few patents. To reliably estimate this effect, vindeburnol was studied in a model of long-term variable-frequency ultrasound (US) exposure at 20–45 kHz in male Wistar rats and BALB/c mice. Vindeburnol was administered chronically for 21 days against a background of simultaneous ultrasound exposure at a dose of 20 mg/kg intraperitoneally (IP). Using four behavioral tests, the sucrose preference test (SPT), the social interaction test (SIT), the open field test (OFT), and the forced swimming test (FST), we found that the treatment with the compound diminished depression-like symptoms in mice and rats. The compound restored the ultrasound-related reduced sucrose consumption to control levels and increased social interaction time in mice and rats compared with those in ultrasound-exposed animals. Vindeburnol showed contraversive results of horizontal and vertical activity in both species and generally did not increase locomotor activity. At the same time, the compound showed a specific effect in the FST, significantly reducing the immobility time. Moreover, we found an increase in norepinephrine, dopamine, and its metabolite levels in the brainstem, as well as an increase in dopamine, 3-methoxytyramine, and 3,4-dihydroxyphenylacetic acid levels in the striatum. We also observed a statistically significant increase in tyrosine hydroxylase (TH) levels in the region containing the locus coeruleus (LC). We suggest that using its distinct chemical structure and pharmacological activity as a starting point could boost antidepressant drug discovery.

show abstract

Section: Resultsmentioning

confidence: 99%

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Zubkov,

Riabova,

Zorkina

et al. 2024

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Rats become vulnerable to depression because of persistent oxidative stress, which could be reversed by antioxidant administration [70]. There are different protection systems and mechanisms in the body to cope with overproduction of pro-oxidants, but they can be intruded upon by different pathological states [65,67,71].…”

Section: Discussionmentioning

confidence: 99%

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

Abramova

Zorkina

Syunyakov

et al. 2021

IJMS

View full text Add to dashboard Cite

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

show abstract

“…Serotonin has been highlighted as a principal neurotransmitter altered in depression; therefore, selective serotonin reuptake inhibitors (SSRI) tend to be the first-line treatment. The monoamine hypothesis of depression [ 59 ] suggests that the deficit of monoamines (serotonin, norepinephrine, and dopamine) in the brain is the basis of the pathogenesis of depressive disorder [ 60 , 61 ].…”

Section: Depression: a Significant Risk Factor For Suicide And Suicid...mentioning

confidence: 99%

Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk

Somoza-Moncada

Turrubiates-Hernández

Muñoz‐Valle

et al. 2023

Nutrients

View full text Add to dashboard Cite

Suicide is one of the leading causes of death worldwide. According to the World Health Organization (WHO), every year, more than 700 thousand people die from this cause. Therefore, suicide is a public health issue. The complex interaction between different factors causes suicide; however, depression is one of the most frequent factors in people who have attempted suicide. Several studies have reported that vitamin D deficiency may be a relevant risk factor for depression, and vitamin D supplementation has shown promising effects in the adjunctive treatment of this mood disorder. Among the beneficial mechanisms of vitamin D, it has been proposed that it may enhance serotonin synthesis and modulate proinflammatory cytokines since low serotonin levels and systemic inflammation have been associated with depression and suicide. The present narrative review shows the potential pathogenic role of vitamin D deficiency in depression and suicide and the potential benefits of vitamin D supplementation to reduce their risk.

show abstract

Molecular Biological Aspects of Depressive Disorders: A Modern View

Cited by 10 publications

References 177 publications

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk

Contact Info

Product

Resources

About