Melatonin adjusts the expression pattern of clock genes in the suprachiasmatic nucleus and induces antidepressant-like effect in a mouse model of seasonal affective disorder

Andras David Nagy, Ayaka Iwamoto, Misato Kawai, Ryosei Goda, Haruka Matsuo, Tsuyoshi Otsuka, Mao Nagasawa, Mitsuhiro Furuse, Shinobu Yasuo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recently, we have shown that C57BL/6J mice exhibit depression-like behavior under short photoperiod and suggested them as an animal model for investigating seasonal affective disorder (SAD). In this study, we tested if manipulations of the circadian clock with melatonin treatment could effectively modify depression-like and anxiety-like behaviors and brain serotonergic system in C57BL/6J mice. Under short photoperiods (8-h light/16-h dark), daily melatonin treatments 2h before light offset have significantly altered the 24-h patterns of mRNA expression of circadian clock genes (per1, per2, bmal1 and clock) within the suprachiasmatic nuclei (SCN) mostly by increasing amplitude in their expressional rhythms without inducing robust phase shifts in them. Melatonin treatments altered the expression of genes of serotonergic neurotransmission in the dorsal raphe (tph2, sert, vmat2 and 5ht1a) and serotonin contents in the amygdala. Importantly, melatonin treatment reduced the immobility in forced swim test, a depression-like behavior. As a key mechanism of melatonin-induced antidepressant-like effect, the previously proposed phase-advance hypothesis of the circadian clock could not be confirmed under conditions of our experiment. However, our findings of modest adjustments in both the amplitude and phase of the transcriptional oscillators in the SCN as a result of melatonin treatments may be sufficient to associate with the effects seen in the brain serotonergic system and with the improvement in depression-like behavior. Our study confirmed a predictive validity of C57BL/6J mice as a useful model for the molecular analysis of links between the clock and brain serotonergic system, which could greatly accelerate our understanding of the pathogenesis of SAD, as well as the search for new treatments.

Original languageEnglish
Pages (from-to)447-457
Number of pages11
JournalChronobiology International
Volume32
Issue number4
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Seasonal Affective Disorder
Suprachiasmatic Nucleus
Melatonin
Antidepressive Agents
Circadian Clocks
Inbred C57BL Mouse
Depression
Genes
Photoperiod
Brain
Social Adjustment
Light
Molecular Models
Amygdala
Synaptic Transmission
Serotonin
Anxiety
Animal Models
Gene Expression
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Melatonin adjusts the expression pattern of clock genes in the suprachiasmatic nucleus and induces antidepressant-like effect in a mouse model of seasonal affective disorder. / Nagy, Andras David; Iwamoto, Ayaka; Kawai, Misato; Goda, Ryosei; Matsuo, Haruka; Otsuka, Tsuyoshi; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu.

In: Chronobiology International, Vol. 32, No. 4, 01.05.2015, p. 447-457.

Research output: Contribution to journalArticle

Nagy, Andras David ; Iwamoto, Ayaka ; Kawai, Misato ; Goda, Ryosei ; Matsuo, Haruka ; Otsuka, Tsuyoshi ; Nagasawa, Mao ; Furuse, Mitsuhiro ; Yasuo, Shinobu. / Melatonin adjusts the expression pattern of clock genes in the suprachiasmatic nucleus and induces antidepressant-like effect in a mouse model of seasonal affective disorder. In: Chronobiology International. 2015 ; Vol. 32, No. 4. pp. 447-457.
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