Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC

Ladurelle, N.; Gabriel, C.; Viggiano, Adela; Mocaër, Elisabeth; Baulieu, Étienne Émile; Bianchi, Massimiliano

doi:10.1007/s00213-011-2597-5

Cited by 49 publications

(43 citation statements)

References 98 publications

(136 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Repeated daily administration (3-4 wk) of different classes of antidepressant drugs have been reported to affect microtubules in the rat hippocampus by changing the ratio of hippocampal α-tubulin isoforms suggestive of increased microtubule dynamics (6,28) and by increasing MAP-2 phosphorylation (22,28). The modulation of microtubule dynamics induced by repeated administrations of antidepressant drugs is a slow process associated to postsynaptic activation of intracellular protein kinases pathways (4) and translocation of Gsa from plasma membrane (29) to cytosol, where it increases microtubule dynamics (30).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague–Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering “depressive-like” behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The hippocampi, amygdalae, and PFC were dissected and prepared for Western Blot analyses as described (28).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been found to be an effective antidepressant and an anxiolytic [6]. Agomelatine synchronizes the circadian rhythm and also ameliorates stress-related changes like depressive symptoms by modulating the cytoskeleton micro tubular dynamics and synaptic markers such as brain derived neurotrophic factor in amygdala and hippocampus [13,14]. Agomelatine antagonizes serotonin 2C receptor which is an important mediator of satiety [15].…”

Section: Discussionmentioning

confidence: 99%

A Study on the Effects of Agomelatine on Food Intake and Body Weight in Restraint Stress Model in Adult Swiss Albino Mice

Priya

Nivedhithaa

Huvaneswari

2017

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objectives: Agomelatine is a novel melatonin (MT) receptor agonist at MT 1 and 2, serotonin receptor antagonist and an effective chronobiotic agent. The study was designed to evaluate the effects of agomelatine on body weight and food intake in restraint stress model in adult Swiss albino mice. Methods:After the approval of Institutional Animal Ethics Committee, 40 male Swiss albino mice were randomly divided into four groups of 10 animals each; two were treatment groups which received 25 mg/kg (low dose) agomelatine, 50 mg/kg (high dose) agomelatine, standard group given trazodone and the control group administered the vehicle (1% hydroxyethyl cellulose [HEC]) intraperitoneally for the last 14 days in the 3 weeks study period. Chronic restraint stress was given for 4 hrs per day for all groups starting from day 0 to 21. Results:Using paired t-test, both 12 hrs (p=0.011) and 24 hrs (p<0.001) food intake in the high dose agomelatine group were significantly increased. Between groups using ANOVA test showed a statistically significant increase in food intake for this group when compared to the control group. Unlike the low dose agomelatine group (p=0.205), the mean body weight in the group treated with high dose agomelatine revealed a statistically significant rise compared to that of the control (p=0.001) in ANOVA test. Conclusion:High dose agomelatine was effective in antagonizing the body weight lowering effect of restraint stress in addition to amelioration of reduced food intake. The study has potentially brought out the additional therapeutic benefit of agomelatine in improving the altered feeding and body weight changes when used in the treatment of the depression.

show abstract

“…Agomelatinin hipokampal yapıda Tyr/Glu-Tub ve MAP-2 gibi mikrotübüler dinamiklerle ilişkili elemanları artırıcı etkilerinin antidepresan etkilerinin yanı sıra bellek üzerine olumlu etkileri ile de ilişkili olabileceği ileri sürülmüştür 89 . Tüm bu veriler agomelatinin öğrenme ve bellek işlevleri üzerine olumlu etkileri bulunabileceği izlenimini vermektedir…”

Section: Agomelatinunclassified

Antidepresan İlaçların Öğrenme ve Bellek Mekanizmasına Etkileri

Berktaş

Kıroğlu

Aksu

2017

Arşiv Kaynak Tarama Dergisi

View full text Add to dashboard Cite

Depression is a psychiatric disease that negatively affects quality of life and workforce. In recent years there is an increase in suggestions that the formation of affective disorders were caused by pathological changes influencing structural plasticity and cell structures. These studies primarily focused on the hippocampal area. Hippocampus is especially important in regards to episodic memory, expressive memory, content and spatial memory. "Neural plasticity", known as long term potentiation of learning and memory mechanisms, was firstly identified and examined in this structure.This phenomenon is believed to be fundamental neuronal mechanisms involved in memory formation. Antidepressant treatment can correct negative effects of learning and memory mechanisms induced by stress. This study reviews studies focusing on effects of antidepressants on learning-memory mechanisms.

show abstract

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC

Abstract: Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT(2C) antagonist properties of the compound.

Cited by 49 publications

References 98 publications

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

A Study on the Effects of Agomelatine on Food Intake and Body Weight in Restraint Stress Model in Adult Swiss Albino Mice

Antidepresan İlaçların Öğrenme ve Bellek Mekanizmasına Etkileri

Contact Info

Product

Resources

About