Pro-BDNF Knockout Causes Abnormal Motor Behaviours and Early Death in Mice

Li, Hua; Lin, Liying; Zhang, Yan; Lim, Yoon Pin; Rahman, Mehreen; Beck, Andrew H.; Al‐Hawwas, Mohammed; Feng, Shiqing; Bobrovskaya, Larisa; Zhou, Xin‐Fu

doi:10.1016/j.neuroscience.2020.05.007

Cited by 9 publications

(6 citation statements)

References 57 publications

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“…One potential process involved in neuronal loss is decreased brain-derived neurotrophic factor (BDNF) via histone modifications to the promoter region associated with downregulation of BDNF transcripts 73 , 74 . Given its role in neuronal maturation and differentiation 75 as well as its neuroprotective effects 76 , low brain levels of BDNF may affect neuronal viability in MDD. This is because BDNF can bind to tropomyosin kinase B (TrkB) receptor which activates the mechanistic target of rapamycin (mTOR) signaling pathway which promotes neuronal growth, proliferation and migration 77 .…”

Section: A Balancing Act: Cell Death and Survivalmentioning

confidence: 99%

Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications

et al. 2022

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Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. More recently, however, there has been a paradigm shift towards a neuroplasticity hypothesis of depression in which downstream effects of antidepressants, such as increased neurogenesis, contribute to improvements in cognition and mood. This review takes a top-down approach to assess how changes in behavior and hippocampal-dependent circuits may be attributed to abnormalities at the molecular, structural and synaptic level. We conclude with a discussion of how antidepressant treatments share a common effect in modulating neuroplasticity and consider outstanding questions and future perspectives.

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Section: A Balancing Act: Cell Death and Survivalmentioning

confidence: 99%

Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications

et al. 2022

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“…Therefore, the reduction of cortical BDNF delivery would result in decreased activity of the cortex and striatum synaptic activity and synaptic loss (Yu et al, 2018). BDNF pro-domain knockout mouse showed impaired righting reflex, abnormal motor behaviors, obvious weight loss and short lifespan, which displayed a Huntington's disease-like phenotype, supporting the BDNF hypothesis in the pathogenesis of HD (Li et al, 2020). Furthermore, low expression of BDNF in HD pathogenesis is potentially mediated by cAMP, MAPK and Ras signaling pathways (Zhou et al, 2021).…”

Section: Brain Derived Neurotrophic Factor and Huntington's Diseasementioning

confidence: 91%

The role of brain derived neurotrophic factor in central nervous system

Qin

et al. 2022

Front. Aging Neurosci.

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Brain derived neurotrophic factor (BDNF) has multiple biological functions which are mediated by the activation of two receptors, tropomyosin receptor kinase B (TrkB) receptor and the p75 neurotrophin receptor, involving in physiological and pathological processes throughout life. The diverse presence and activity of BDNF indicate its potential role in the pathogenesis, progression and treatment of both neurological and psychiatric disorders. This review is to provide a comprehensive assessment of the current knowledge and future directions in BDNF-associated research in the central nervous system (CNS), with an emphasis on the physiological and pathological functions of BDNF as well as its potential treatment effects in CNS diseases, including depression, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and cerebral ischemic stroke.

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“…However, activating the p75NTR receptor signaling pathways requires binding to the adaptor proteins and sortilin to bind to proNTs [ 1 , 31 ]. In addition, a balance between proNTs and mature NTs is necessary for the proper development and function of the CNS [ 3 ], as was discovered in the case of proBDNF and BDNF in a study with KO proBDNF mice performed by Hua Li et al [ 38 ]. This study found proBDNF to be essential for cell survival, the development of the cells within CNS and the GABAanergic system, promoting motor behavior, and can even cause Huntington’s disease phenotype in mice [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…NTs signaling is key to the development of essential functions in the CNS [ 1 , 3 , 17 , 19 , 20 , 31 , 32 , 38 ]. Several signaling pathways are triggered by Trk engagement, but the best characterized are the binding-inducing phosphatidylinositol 3 kinases (PI3K)-Akt, the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK), and the phosphoinositide-specific phospholipase C-γ1 (PLCγ1) [ 1 , 20 , 32 , 33 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

“…The MAPK-ERK pathway is modulated by a signaling cascade that includes Ras, which is involved in neuronal differentiation and cell survival [ 22 , 31 , 33 ] and leads to the activation of MAPK-ERK signaling [ 1 , 20 , 32 ]. MAPK-ERK is involved in several functions and events inside the CNS, such as synaptic plasticity and cell survival [ 19 , 38 ]. On the other hand, the signaling via PI3K-Akt can be activated independently or dependently on Ras [ 33 ], and in the case of most neuronal cells, the activation of PI3K through Ras induces cell survival signals [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System

Böhmwald

Andrade

Mora

et al. 2022

IJMS

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Neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), NT-4, and NT-5, are proteins involved in several important functions of the central nervous system. The activation of the signaling pathways of these neurotrophins, or even by their immature form, pro-neurotrophins, starts with their recognition by cellular receptors, such as tropomyosin receptor kinase (Trk) and 75 kD NT receptors (p75NTR). The Trk receptor is considered to have a high affinity for attachment to specific neurotrophins, while the p75NTR receptor has less affinity for attachment with neurotrophins. The correct functioning of these signaling pathways contributes to proper brain development, neuronal survival, and synaptic plasticity. Unbalanced levels of neurotrophins and pro-neurotrophins have been associated with neurological disorders, illustrating the importance of these molecules in the central nervous system. Furthermore, reports have indicated that viruses can alter the normal levels of neurotrophins by interfering with their signaling pathways. This work discusses the importance of neurotrophins in the central nervous system, their signaling pathways, and how viruses can affect them.

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Pro-BDNF Knockout Causes Abnormal Motor Behaviours and Early Death in Mice

Cited by 9 publications

References 57 publications

Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications

Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications

The role of brain derived neurotrophic factor in central nervous system

Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System

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