Single and chronic l-serine treatments exert antidepressant-like effects in rats possibly by different means

Nagasawa, Mao; Otsuka, Tsuyoshi; Togo, Yuki; Yamanaga, Masakazu; Yoshida, Junki; Uotsu, Nobuo; Teramoto, Shokichi; Yasuo, Shinobu; Furuse, Mitsuhiro

doi:10.1007/s00726-017-2448-8

Cited by 16 publications

(12 citation statements)

References 36 publications

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“…In addition, in the case of acute treatment, the concentration of L-Ser in plasma was found to have increased eightfold 30 min after the oral administration, and that in the hippocampus and the cortex also increased [ 25 ]. On the other hand, as has been reported in previous research using rats [ 17 ], chronic treatments do not affect L-Ser levels in the plasma and brain. Thus, there is a broad difference in metabolism and behaviors between single and chronic L-Ser treatments.…”

Section: Discussionsupporting

confidence: 75%

“…The reduction might have been caused by changes in the brain levels of D-Ser, a metabolite of L-Ser, which suppresses intake of high-preference food [ 23 ]. In rats chronically supplemented with L-Ser, D-Ser levels in the brain increased, while L-Ser in the brain, as well as L-Ser and D-Ser in the plasma, did not increase [ 17 ]. These data are comparable with our data showing the concentration of L-Ser in plasma not to have changed.…”

Section: Discussionmentioning

confidence: 99%

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Dietary L-serine modifies free amino acid composition of maternal milk and lowers the body weight of the offspring in mice

Nagamachi

Nishigawa

Takakura

et al. 2018

The Journal of Veterinary Medical Science

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The growth of offspring is affected not only by the protein in maternal milk but also by the free amino acids (FAAs) contained in it. L-Serine (L-Ser) is known as an important FAA for the development of the central nervous system and behavioral activity. However, it is not clear whether L-Ser is transported into the pool of FAAs contained in milk and thereby affects the growth of offspring. Using mice, the current study investigated the effects of dietary L-Ser during pregnancy and lactation on milk and plasma FAA composition, as well as on growth, behavior, and plasma FAAs of offspring. Dietary L-Ser did not significantly affect the maternal, anxiety-like, or cognitive behaviors of either the dam or the offspring. The FAA composition notably differed between plasma and milk in dams. In milk, dietary L-Ser increased free L-Ser levels, while glutamic acid, L-alanine, D-alanine and taurine levels were decreased. The body weight of the offspring was lowered by dietary L-Ser. The concentrations of plasma FAAs in 13-day-old offspring (fed only milk) were not altered, but 20-day-old offspring (fed both milk and parental diet) showed higher plasma L-Ser and D-Ser concentrations as a result of the dietary L-Ser treatment. In conclusion, the present study found that dietary L-Ser transported easily from maternal plasma to milk and that dietary L-Ser treatment could change the FAA composition of milk, but that an enhanced level of L-Ser in milk did not enhance the plasma L-Ser level in the offspring.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Dietary L-serine modifies free amino acid composition of maternal milk and lowers the body weight of the offspring in mice

Nagamachi

Nishigawa

Takakura

et al. 2018

The Journal of Veterinary Medical Science

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“…S5). A previous study showed that chronic L-serine treatments exert antidepressant-like effects on Wistar Kyoto rats 33 . The discrepancy between our study and the previous report might be due to the differences in animal models.…”

Section: Fluoxetine Stimulates Rankl Secretion By Bmas Through Cox-2/mentioning

confidence: 96%

Long-term use of fluoxetine accelerates bone loss through the disruption of sphingolipids metabolism in bone marrow adipose tissue

Zhang

Zhao

et al. 2020

Transl Psychiatry

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Fluoxetine is a commonly prescribed antidepressant, and the mechanisms of increased bone fragility with its longterm use remain largely unknown. Here, we show that long-term administration of fluoxetine induces the disruption of sphingolipids metabolism in bone marrow adipose tissue (BMAT)through the inhibition of acid sphingomyelinase (ASM). Similarly, a significant reduction of the bone volume was observed in mice with ASM knockout (Smpd1 −/−). In detail, inhibition of ASM by fluoxetine reduces the sphingosine-1-phosphate (S1P) level in bone marrow adipocytes, leading to the increase of receptor activator of nuclear factor-kappa-Β ligand (RANKL) secretion, a key regulator for the activation of osteoclastogenesis and bone loss, through the upregulation of cyclooxygenase-2 and its enzymatic product prostaglandin E2 (COX-2/PGE2). In contrast, overexpression of ASM by cisplatin normalizes fluoxetine-induced RANKL overproduction. Furthermore, we conducted a clinical trial with L-serine, a precursor of sphingolipids biosynthesis. The results show that oral supplementation of L-serine (250 mg//kg/d) prevents the acceleration of bone loss caused by long-term fluoxetine (12 months) in postmenopausal women with major depressive disorder (mean total hip bone mineral density reduction: −2.0% vs −1.1%, P = 0.006). Our study provides new insights and potential treatment strategy on the bone loss caused by long-term use of fluoxetine.

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“…The release of d -serine can be triggered by glutamate [39], so a reduced glutamate level might lessen the release of serine in our present study. The antidepressant effects of acute and chronic d -serine or l -serine treatment have been investigated in serotonin depletion, learned helplessness, and the OBX paradigm [37,39,40]. Sarcosine, also as a co-agonist of NMDAR, could alleviate depressive symptoms in patients and reverse behavioral deficits in CUMS-induced animals, and its antidepressant effects were superior to citalopram [41].…”

Section: Discussionmentioning

confidence: 99%

Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine

Zhou

Xue

Wang

et al. 2019

IJMS

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An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.

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Single and chronic l-serine treatments exert antidepressant-like effects in rats possibly by different means

Cited by 16 publications

References 36 publications

Dietary L-serine modifies free amino acid composition of maternal milk and lowers the body weight of the offspring in mice

Dietary L-serine modifies free amino acid composition of maternal milk and lowers the body weight of the offspring in mice

Long-term use of fluoxetine accelerates bone loss through the disruption of sphingolipids metabolism in bone marrow adipose tissue

Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine

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