Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice

Ahuja, Palak; Ng, Chun Fai; Pang, Brian Pak Shing; Chan, Wing Suen; Tse, Margaret Chui Ling; Bi, Xinyi; Kwan, Hiu-Lam Rachel; Brobst, Daniel; Herlea‐Pana, Oana; Yang, Xiuying; Du, Guanhua; Saengnipanthkul, Sukit; Noh, Hye Lim; Jiao, Baowei; Kim, Jason K.; Lee, Chi Wai; Ye, Keqiang; Chan, Chi Bun

doi:10.1080/15548627.2021.1985257

Cited by 56 publications

(54 citation statements)

References 82 publications

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“…BDNF has also been shown to be involved in muscle satellite cell regulation. In addition to its role in fat burning and muscle contraction, BDNF is interested in increasing muscle fiber diameter [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of combined locomotor training and aerobic exercise on increasing handgrip strength in elderly with locomotive syndrome: A randomised controlled trial

Nayasista

Tinduh

Pawana

et al. 2022

Annals of Medicine &Amp; Surgery

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Section: Discussionmentioning

confidence: 99%

Effect of combined locomotor training and aerobic exercise on increasing handgrip strength in elderly with locomotive syndrome: A randomised controlled trial

Nayasista

Tinduh

Pawana

et al. 2022

Annals of Medicine &Amp; Surgery

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“…This conclusion is in line with evidence that activation of TrkB by its agonist 7,8-DHF initiates the CREB/PGC-1α cascade to provoke mitochondrial biogenesis and cellular respiration in skeletal muscle [ 53 ]. However, further mechanisms responsible for the effect of 7,8-DHF on restoration of brain mitochondrial bioenergetics, including an activation of mitophagy, mitochondrial remodelling and a consequent activation of mitochondrial biogenesis [ 63 ], cannot be excluded and merit to be deeply investigated.…”

Section: Discussionmentioning

confidence: 99%

Impaired Brain Mitochondrial Bioenergetics in the Ts65Dn Mouse Model of Down Syndrome Is Restored by Neonatal Treatment with the Polyphenol 7,8-Dihydroxyflavone

et al. 2021

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Down syndrome (DS), a major genetic cause of intellectual disability, is characterized by numerous neurodevelopmental defects. Previous in vitro studies highlighted a relationship between bioenergetic dysfunction and reduced neurogenesis in progenitor cells from the Ts65Dn mouse model of DS, suggesting a critical role of mitochondrial dysfunction in neurodevelopmental alterations in DS. Recent in vivo studies in Ts65Dn mice showed that neonatal supplementation (Days P3–P15) with the polyphenol 7,8-dihydroxyflavone (7,8-DHF) fully restored hippocampal neurogenesis. The current study was aimed to establish whether brain mitochondrial bioenergetic defects are already present in Ts65Dn pups and whether early treatment with 7,8-DHF positively impacts on mitochondrial function. In the brain and cerebellum of P3 and P15 Ts65Dn pups we found a strong impairment in the oxidative phosphorylation apparatus, resulting in a deficit in mitochondrial ATP production and ATP content. Administration of 7,8-DHF (dose: 5 mg/kg/day) during Days P3–P15 fully restored bioenergetic dysfunction in Ts65Dn mice, reduced the levels of oxygen radicals and reinstated the hippocampal levels of PGC-1α. No pharmacotherapy is available for DS. From current findings, 7,8-DHF emerges as a treatment with a good translational potential for improving mitochondrial bioenergetics and, thus, mitochondria-linked neurodevelopmental alterations in DS.

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“…Furthermore, BDNF deficiency in the heterozygous Bdnf knockout mice (BDNF+/−) sensitizes their hepatocytes to ER stress-induced cell death, which is a common consequence seen in the obese tissues [ 27 ]. Hence, the FA-induced Bdnf expression in the livers of mice after high fat diet (HFD) feeding might prevent the ectopic lipid accumulation and the related adverse metabolic consequences [ 26 , 28 ]. Mechanistically, mBDNF destabilizes the TrkB isoform, TrkB.T1, in hepatocytes to protect the cells from lipotoxicity [ 25 ].…”

Section: Bdnf In Livermentioning

confidence: 99%

“…A similar observation of AMPK-induced FAO was found in C2C12 after TrkB stimulation by 7,8-DHF [ 69 ]. Our recent report further demonstrated that BDNF activated AMPK in the muscle cells via triggering an intracellular Ca 2+ surge, which acted through the calmodulin K kinase 2 (CamKK2) to induce AMPK phosphorylation [ 28 ]. AMPK is an imperative metabolic sensor that balances the energy metabolism, whose activity is provoked under an energy-deficient state.…”

Section: Bdnf In Skeletal Musclementioning

confidence: 99%

“…At the molecular level, metabolic flexibility relies on the configuration of signaling pathways that manage nutrient sensing, uptake, transport, storage, and utilization. In cultured C2C12 myotubes, BDNF secretion was provoked by the biochemical factors of fasting, including glucose depletion, amino acid restriction, and β-hydroxybutyrate (βHB) stimulation [ 28 , 60 , 80 , 81 ]. We and others have also shown that Bdnf expression in Skm is increased during fasting, suggesting mBDNF might be involved in regulating metabolism to move through the fed-fast cycle [ 60 , 81 ].…”

Section: Bdnf In Skeletal Musclementioning

confidence: 99%

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Is Brain-Derived Neurotrophic Factor a Metabolic Hormone in Peripheral Tissues?

Chan

2022

Biology

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Brain-derived neurotrophic factor (BDNF) is an important growth factor in the central nervous system. In addition to its well-known activities in promoting neuronal survival, neuron differentiation, and synaptic plasticity, neuronal BDNF also regulates energy homeostasis by modulating the hypothalamus’s hormonal signals. In the past decades, several peripheral tissues, including liver, skeletal muscle, and white adipose tissue, were demonstrated as the active sources of BDNF synthesis in response to different metabolic challenges. Nevertheless, the functions of BDNF in these tissues remain obscure. With the use of tissue-specific Bdnf knockout animals and the availability of non-peptidyl BDNF mimetic, increasing evidence has reported that peripheral tissues-derived BDNF might play a significant role in maintaining systemic metabolism, possibly through the regulation of mitochondrial dynamics in the various tissues. This article reviews the autocrine/paracrine/endocrine functions of BDNF in non-neuronal tissues and discusses the unresolved questions about BDNF’s function.

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Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice

Cited by 56 publications

References 82 publications

Effect of combined locomotor training and aerobic exercise on increasing handgrip strength in elderly with locomotive syndrome: A randomised controlled trial

Effect of combined locomotor training and aerobic exercise on increasing handgrip strength in elderly with locomotive syndrome: A randomised controlled trial

Impaired Brain Mitochondrial Bioenergetics in the Ts65Dn Mouse Model of Down Syndrome Is Restored by Neonatal Treatment with the Polyphenol 7,8-Dihydroxyflavone

Is Brain-Derived Neurotrophic Factor a Metabolic Hormone in Peripheral Tissues?

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