Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus

Moro, Kazuhisa; Shiotani, Akiko; Watabe, Kazuhiko; Takeda, Yasuo; Saito, Koichiro; Mori, Yuko; Ogawa, Kaoru

doi:10.1016/j.brainres.2005.12.119

Cited by 27 publications

(25 citation statements)

References 48 publications

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“…BDNF has been shown to affect the proliferation, survival, and differentiation of NSCs in vitro and in vivo [12][13][14]. The potential of BDNF gene transfer for the treatment of CNS injury has been demonstrated [15]. Following acute cervical spinal cord injury, viral-mediated gene transfer of BDNF prevented rubrospinal neuronal atrophy and enhanced the growth propensity of injured neurons by stimulating regenerationassociated gene expression [16].…”

Section: Introductionmentioning

confidence: 99%

Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury

Kong

et al. 2011

Neurochem Res

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Brain-derived neurotrophic factor (BDNF) plays an essential regulatory role in the survival and differentiation of various neural cell types during brain development and after injury. In this study, we used neural stem cells (NSCs) genetically modified to encode BDNF gene (BDNF/NSCs) and naive NSCs transplantation and found that BDNF/NSCs significantly improved neurological motor function following traumatic brain injury (TBI) on selected behavioral tests. Our data clearly demonstrate that the transplantation of BDNF/NSCs causes overexpression of BDNF in the brains of TBI rats. The number of surviving engrafted cells and the proportion of engrafted cells with a neuronal phenotype were significantly greater in BDNF/NSCs than in naive NSCs-transplanted rats. The expression of pre- and post-synaptic proteins and a regeneration-associated gene in the BDNF/NSCs-transplanted rats was significantly increased compared to that in NSCs-transplanted rats, especially at the early stage of post-transplantation. These data suggest that neurite growth and overexpression of synaptic proteins in BDNF/NSCs-transplanted rats are associated with the overexpression of BDNF, which is hypothesized to be one of the mechanisms underlying the improved functional recovery in motor behavior at the early stage of cell transplantation following TBI. Therefore, the protective effect of the BDNF-modified NSCs transplantation is greater than that of the naive NSCs transplantation.

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Section: Introductionmentioning

confidence: 99%

Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury

Kong

et al. 2011

Neurochem Res

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“…However, it is difficult to retain them at injury sites because they easily diffuse. In order to maintain active concentrations, previous studies have employed multiple injections, adenoviral vectors overexpressing BDNF or GDNF, or fusion proteins such as CBD-BDNF and LBD-BDNF (3,7,13,34,35). However, the risk of surgery, immunological rejection, and costs with these methods would all be increased.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived and glial cell line-derived neurotrophic factor fusion protein immobilization to laminin

Wang

Yuan

et al. 2016

Experimental and Therapeutic Medicine

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Damage to the recurrent laryngeal nerve often causes hoarseness, dyspnea, dysphagia, and sometimes asphyxia due to vocal cord paralysis which result in a reduction of quality of life. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) play critical roles in peripheral nerve regeneration. However, methods for efficiently delivering these molecules are lacking, which limits their use in clinical applications. The present study reports an effective strategy for targeting BDNF and GDNF to laminin by fusing the N-terminal domains of these molecules with agrin (NtA). More specifically, laminin-binding efficacy was assessed and sustained release assays of the delivery of BDNF or GDNF fused with NtA (LBD-BDNF or LBD-GDNF) to laminin were conducted in vitro. In addition, the bioactivity of LBD-BDNF and LBD-GDNF on laminin in vitro was investigated. LBD-BDNF and LBD-GDNF were each able to specifically bind to laminin and maintain their activity in vitro. Moreover, neurotrophic factors with NtA retained higher concentrations and bioactivity levels compared with those without NtA. The ratio of LBD-BDNF and LBD-GDNF that produced optimal effects was 4:6. BDNF and GDNF fused with NtA were effective in specifically binding to laminin. As laminin is a major component of the extracellular matrix, LBD-BDNF and LBD-GDNF may prove useful in the repair of peripheral nerve injuries.

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“…The effect of BDNF on survival of lesioned motoneurons has been studied in other neonatal models, resulting in the prevention of the axotomy-induced cell death of facial and spinal motoneurons [63,110,111,113]. In addition, adenoviral gene therapy using recombinant adenovirus vectors encoding BDNF cDNAs has shown the ability to promote the survival of spinal, facial or ambiguous nucleus motoneurons after avulsion in adult rats [120,121]. …”

Section: Neurotrophins Rescue Extraocular Motoneurons From Axotomymentioning

confidence: 99%

Functional Diversity of Neurotrophin Actions on the Oculomotor System

Benítez‐Temiño¹,

Carrizosa²,

Morcuende³

et al. 2016

IJMS

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Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase). In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review, we summarize these evidences and discuss them in the context of other motor systems.

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Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus

Cited by 27 publications

References 48 publications

Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury

Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury

Brain-derived and glial cell line-derived neurotrophic factor fusion protein immobilization to laminin

Functional Diversity of Neurotrophin Actions on the Oculomotor System

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