Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus

Kunisawa, Kazuo; Kido, Kiwamu; Nakashima, N.; Matsukura, Takuya; Nabeshima, Toshitaka; Hiramatsu, Masayuki

doi:10.1016/j.ejphar.2016.12.007

Cited by 31 publications

(29 citation statements)

References 41 publications

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“…In contrast to the cortex, palmitoylcarnitine and betaine change conversely in the brain region of the hippocampus in response to subacute TBI. The evidence in previous studies suggests that betaine treatment plays a vital role in synaptic plasticity associated with learning and memory ( Kunisawa et al, 2017 ). An increase in palmitoylcarnitine plays an important role in the decrease of fatty acid beta oxidation at the acute time point, which is consistent with our study ( Ojuka et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Analysis of Hippocampus and Cortex in a Rat Model of Traumatic Brain Injury in the Subacute Phase

Zheng

Zhou

et al. 2020

Front. Neurosci.

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Traumatic brain injury (TBI) is a complex and serious disease as its multifaceted pathophysiological mechanisms remain vague. The molecular changes of hippocampal and cortical dysfunction in the process of TBI are poorly understood, especially their chronic effects on metabolic profiles. Here we utilize metabolomics-based liquid chromatography coupled with tandem mass spectrometry coupled with bioinformatics method to assess the perturbation of brain metabolism in rat hippocampus and cortex on day 7. The results revealed a signature panel which consisted of 13 identified metabolites to facilitate targeted interventions for subacute TBI discrimination. Purine metabolism change in cortical tissue and taurine and hypotaurine metabolism change in hippocampal tissue were detected. Furthermore, the associations between the metabolite markers and the perturbed pathways were analyzed based on databases: 64 enzyme and one pathway were evolved in TBI. The findings represented significant profiling changes and provided unique metabolite–protein information in a rat model of TBI following the subacute phase. This study may inspire scientists and doctors to further their studies and provide potential therapy targets for clinical interventions.

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Section: Discussionmentioning

confidence: 99%

Metabolomics Analysis of Hippocampus and Cortex in a Rat Model of Traumatic Brain Injury in the Subacute Phase

Zheng

Zhou

et al. 2020

Front. Neurosci.

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“…Betaine, also known as trimethylglycine, is a water-soluble compound that penetrates the blood-brain barrier and exhibits high distribution to the hippocampus in vitro [14,15]. Betaine has shown various pharmacological effects, such as antiepileptic, neuroprotective, and memory-improving effects [14,16,17,18]. In particular, it acts as a methyl donor to interfere with depression caused by hyperhomocysteinemia [19].…”

Section: Introductionmentioning

confidence: 99%

Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells

et al. 2019

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Microglia mediate multiple facets of neuroinflammation. They can be phenotypically divided into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2) with different physiological characteristics and biological functions in the inflammatory process. Betaine has been shown to exert anti-inflammatory effects. In this study, we aimed to verify the anti-inflammatory effects of betaine and elucidate its possible molecular mechanisms of action in vitro. Lipopolysaccharide (LPS)-activated microglial cells were used as an inflammatory model to study the anti-inflammatory efficacy of betaine and explore its mechanism of regulating microglial polarisation by investigating the morphological changes and associated inflammatory changes. Cytokine and inflammatory mediator expression was also measured by ELISA, flow cytometry, immunofluorescence, and western blot analysis. Toll-like receptor (TLR)-myeloid differentiation factor 88 (Myd88)-nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, p-IκB, IκB kinase (IKK), and p-IKK expression was determined by western blot analysis. Betaine significantly mitigated the production of pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It promoted the conversion of the microglia from M1 to M2 phenotype by decreasing the expression of inducible nitric oxide synthase and CD16/32 and by increasing that of CD206 and arginase-1. Betaine treatment inhibited the TLR4/NF-κB pathways by attenuating the expression of TLR4-Myd88 and blocking the phosphorylation of IκB and IKK. In conclusion, betaine could significantly alleviate LPS-induced inflammation by regulating the polarisation of microglial phenotype; thus, it might be an effective therapeutic agent for neurological disorders.

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“…Osthole further blocked the reduction of NGF levels in experimental autoimmune encephalomyelitis mice [45]. In addition, the effects of betaine in Goji berry on memory function have been demonstrated by accumulated reports [46][47][48]. The pharmacological activities of these compounds may induce the NGF-mediated memory-enhancing effects of KYJ.…”

Section: Discussionmentioning

confidence: 93%

The Mixture of Gotu Kola, Cnidium Fruit, and Goji Berry Enhances Memory Functions by Inducing Nerve-Growth-Factor-Mediated Actions Both In Vitro and In Vivo

et al. 2020

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Nerve growth factor (NGF), a typical neurotrophin, has been characterized by the regulation of neuronal cell differentiation and survival involved in learning and memory functions. NGF has a main role in neurite extension and synapse formation by activating the cyclic adenosine monophosphate-response-element-binding protein (CREB) in the hippocampus. The purpose of this study was to determine whether a mixture of Gotu Kola, Cnidium fruit, and Goji berry (KYJ) enhances memory function by inducing NGF-mediated actions both in vitro and in vivo. The KYJ combination increased NGF concentration and neurite length in C6 glioma and N2a neuronal cells, respectively. Additionally, we discovered memory-enhancing effects of KYJ through increased NGF-mediated synapse maturation, CREB phosphorylation, and cell differentiation in the mouse hippocampus. These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities.

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Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus

Cited by 31 publications

References 41 publications

Metabolomics Analysis of Hippocampus and Cortex in a Rat Model of Traumatic Brain Injury in the Subacute Phase

Metabolomics Analysis of Hippocampus and Cortex in a Rat Model of Traumatic Brain Injury in the Subacute Phase

Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells

The Mixture of Gotu Kola, Cnidium Fruit, and Goji Berry Enhances Memory Functions by Inducing Nerve-Growth-Factor-Mediated Actions Both In Vitro and In Vivo

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