Effects of tamoxifen and glutamate and glutamine levels in brain regions in repeated sleep deprivation–induced mania model in mice

Ozakman, Selda; Gören, M. Zafer; Nurten, Asiye; Tekin, Nurdan; Kalayci, Rivaze; Enginar, Nurhan

doi:10.1007/s00210-020-02001-1

Cited by 6 publications

(8 citation statements)

References 62 publications

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“…Sleep deprivation (SD) has been reported to perturb endocrinal and metabolic functions and the immune system of the brain (6)(7)(8). Animal studies have suggested that rodents exposed to SD can act as a model of mania (9)(10)(11). Rodents exposed to SD show manic-like behaviors, including hyperlocomotion, irritability, hypersexuality, and aggressiveness, as observed during the manic phase in patients with bipolar disorder (BPD) (9)(10)(11)(12).…”

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confidence: 99%

“…Animal studies have suggested that rodents exposed to SD can act as a model of mania (9)(10)(11). Rodents exposed to SD show manic-like behaviors, including hyperlocomotion, irritability, hypersexuality, and aggressiveness, as observed during the manic phase in patients with bipolar disorder (BPD) (9)(10)(11)(12). The administration of mood stabilizers, such as lithium and valproic acid, which are used for the prevention and relief of the manic phase in BPD, also reduces these manic-like behaviors in rodents experiencing SD (13)(14)(15)(16).…”

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confidence: 99%

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REM-Sleep Deprivation Induces Mitochondrial Biogenesis in the Rat Hippocampus

Kim

2022

In Vivo

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Background/Aim: Sleep loss is proposed as a trigger for manic episodes in bipolar disorder in humans. It has been shown that sleep and wakefulness can affect changes in mitochondrial gene expression, oxidative phosphorylation (OXPHOS) activity, and morphology in the brain. In this study, we investigated alterations in mitochondrial bioenergetic function in the brain of rats after 72-h rapid eye movement sleep deprivation (REM-SD). Materials and Methods: Alterations in the mitochondrial DNA (mtDNA) copy number were detected in the prefrontal cortex and hippocampus through amplification of mitochondrially encoded NADH dehydrogenase 1 (mt-Nd1) gene using quantitative real-time polymerase chain reaction. The expression levels of mitochondrial biogenesis-related proteins such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), cytochrome c oxidase subunit 4I1 (COX4I1) and sirtuin 3 (SIRT3) were assessed using western blot analysis and immunohistochemistry. Results: We found that REM-SD significantly increased the mtDNA copy number in the hippocampus but not in the prefrontal cortex. In addition, REM-SD increased the protein expression of COX4I1 in the hippocampus. Furthermore, we observed manic-like behaviors in rats exposed to 72-h REM-SD. REM-SD increased locomotion in the open-field test and the time spent in open arms in the elevated plus-maze test. Conclusion: REM-SD may induce mitochondrial dysfunction in the brain, which may be involved in the induction of mania.

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confidence: 99%

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confidence: 99%

REM-Sleep Deprivation Induces Mitochondrial Biogenesis in the Rat Hippocampus

Kim

2022

In Vivo

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“… 5 , 6 A number of animal studies have proposed rodents subjected to sleep deprivation as a mania model. 7 , 8 , 9 Indeed, sleep‐deprived (SD) rodents exhibit manic‐like behaviors, including hyperlocomotion, irritability, impulsivity, and aggressiveness, as observed during the manic phase in patients with BPD. 7 , 8 , 9 , 10 …”

Section: Introductionmentioning

confidence: 99%

“…5,6 A number of animal studies have proposed rodents subjected to sleep deprivation as a mania model. [7][8][9] Indeed, sleep-deprived (SD) rodents exhibit maniclike behaviors, including hyperlocomotion, irritability, impulsivity, and aggressiveness, as observed during the manic phase in patients with BPD. [7][8][9][10] MicroRNAs (miRNAs) are highly conserved small non-coding RNAs across species, with ~22 nucleotides in length.…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] Indeed, sleep-deprived (SD) rodents exhibit maniclike behaviors, including hyperlocomotion, irritability, impulsivity, and aggressiveness, as observed during the manic phase in patients with BPD. [7][8][9][10] MicroRNAs (miRNAs) are highly conserved small non-coding RNAs across species, with ~22 nucleotides in length. In animal cells, miRNAs bind to complementary sequences at the 3′-untranslated region (3′-UTR) of their target mRNAs, promoting translational repression and mRNA degradation by deadenylation and decapping.…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of microRNA‐330‐5p induces manic‐like behaviors in REM sleep‐deprived rats by enhancing tyrosine hydroxylase expression

Leem

Kim

et al. 2023

CNS Neurosci Ther

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Aim In our pilot study, we found an increase in tyrosine hydroxylase (Th) mRNA expression in the prefrontal cortex of 72‐h REM sleep‐deprived (SD) rats, a mania model. Additionally, the expression levels of miR‐325‐3p, miR‐326‐3p, and miR‐330‐5p, the predicted target miRNAs on TH, were significantly decreased. Based on these results, in this study, we investigated whether miRNA‐325‐3p, miR‐326‐3p, and miR‐330‐5p modulate TH and manic‐like behaviors in SD rats. Methods Manic‐like behaviors were assessed using the open field test (OFT) and elevated plus‐maze (EPM) test. The direct binding activity of miRNAs to the 3′‐untranslated region (3′‐UTR) of the Th gene was measured in HEK‐293 cells using a luciferase reporter system. We also examined mRNA and protein expression of TH after intracerebroventricular (ICV) injection of miR‐330‐5p agomir to SD rats, along with manic‐like behaviors. Results We observed an upregulation in mRNA and protein expression of TH and downregulation in miRNA‐325‐3p, miR‐326‐3p, and miR‐330‐5p expressions in the prefrontal cortex of SD rats, together with increased manic‐like behaviors. The luciferase reporter assay showed that miR‐330‐5p could repress TH expression through direct binding to its target site in the 3′‐UTR of Th, whereas miR‐326‐3p and miR‐330‐5p could not. In addition, ICV injection of miR‐330‐5p agomir alleviated the increase in TH expression in the prefrontal cortex of SD rats and manic‐like behaviors. Conclusions TH expression regulation through miR‐330‐5p may be implicated in the pathophysiology of mania in SD rats.

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Circadian Regulation of the Lactate Metabolic Kinetics in Mice Using the [1H-13C]-NMR Technique

Chen,

Wu,

et al. 2024

Mol Neurobiol

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Lactate is not only the energy substrate of neural cells, but also an important signal molecule in brain. In modern societies, disturbed circadian rhythms pose a global challenge. Therefore, exploring the in uence of circadian period on lactate and its metabolic kinetics is essential for the advancement of neuroscienti c research. In the present study, mice were infused [3-13 C] lactate through the tail vein for a duration of two minutes. After 30 minutes lactate metabolism, the animals were sacri ced and the brain tissue was extracted and tested. And then the [ 1 H-13 C] NMR technology was employed to investigate the kinetic information of lactate metabolism in different brain regions during various time periods and acute sleep deprivation, to detect the enrichment of various neurochemicals. The results revealed uctuating lactate concentrations in the brain throughout the day, with lower levels during light periods and higher levels during dark periods.Most metabolites displayed strong sensitivity to circadian rhythm, exhibiting signi cant day-night variations.Conversely, only a few metabolites showed changes after acute sleep deprivation, primarily in the temporal brain region. Interestingly, in contrast to brain lactate metabolism, liver lactate metabolism exhibited a signi cant increase following acute sleep deprivation. This study explored the kinetics of lactate metabolism, hinted at potential clinical implications for disorders involving circadian rhythm disturbances, and providing a new research basis for clinical exploration of brain lactate metabolism.

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Effects of tamoxifen and glutamate and glutamine levels in brain regions in repeated sleep deprivation–induced mania model in mice

Cited by 6 publications

References 62 publications

REM-Sleep Deprivation Induces Mitochondrial Biogenesis in the Rat Hippocampus

REM-Sleep Deprivation Induces Mitochondrial Biogenesis in the Rat Hippocampus

Downregulation of microRNA‐330‐5p induces manic‐like behaviors in REM sleep‐deprived rats by enhancing tyrosine hydroxylase expression

Circadian Regulation of the Lactate Metabolic Kinetics in Mice Using the [1H-13C]-NMR Technique

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