Primary Structure and Biological Activity of Human Brain-Derived Neurotrophic Factor

Rosenthal, Arnon; Goeddel, David V.; Nguyen, Thomas; Martin, Evelyn; Burton, LE; Shih, Ai; Laramee, Gary R.; Wurm, Franziska; Mason, Ariel; Nikolics, Károly; Winslow, John

doi:10.1210/endo-129-3-1289

Cited by 75 publications

(28 citation statements)

References 28 publications

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“…The anti‐BDNF antibody recognizes a protein band with a relative mw of about 13 kDa (Figure 2), in agreement with the reported mw of the monomeric form of the protein (Rosenthal et al., 1991). As shown in Figure 2, the molecular mass of the hippocampal BDNF protein is very close to that of the rhBDNF (Leibrock et al., 1989).…”

Section: Resultsmentioning

confidence: 99%

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

et al. 2017

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IntroductionThe selective breeding of Roman High‐ (RHA) and Low‐Avoidance (RLA) rats for, respectively, rapid versus poor acquisition of the active avoidance response has generated two distinct phenotypes differing in many behavioral traits, including coping strategies to aversive conditions. Thus, RLA rats are considered as a genetic model of vulnerability to stress‐induced depression whereas RHA rats are a model of resilience to that trait. Besides the monoamine hypothesis of depression, there is evidence that alterations in neuronal plasticity in the hippocampus and other brain areas are critically involved in the pathophysiology of mood disorders.Materials and MethodsWestern blot (WB) and immunohistochemistry were used to investigate the basal immunochemical occurrence of brain‐derived neurotrophic factor (BDNF) and its high‐affinity tyrosine‐kinase receptor trkB in the dorsal and ventral hippocampus of adult RHA and RLA rats.Results WB analysis indicated that the optical density of BDNF‐ and trkB‐positive bands in the dorsal hippocampus is, respectively, 48% and 25% lower in RLA versus RHA rats. Densitometric analysis of BDNF‐ and trkB‐like immunoreactivity (LI) in brain sections showed that BDNF‐LI is 24% to 34% lower in the different sectors of the Ammon's horn of RLA versus RHA rats, whereas line‐related differences are observed in the dentate gyrus (DG) only in the ventral hippocampus. As for trkB‐LI, significant differences are observed only in the dorsal hippocampus, where density is 23% lower in the DG of RLA versus RHA rats, while no differences across lines occur in the Ammon's horn.ConclusionThese findings support the hypothesis that a reduced BDNF/trkB signaling in the hippocampus of RLA versus RHA rats may contribute to their more pronounced vulnerability to stress‐induced depression.

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Section: Resultsmentioning

confidence: 99%

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

et al. 2017

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“…Eighty per cent of BDNF protein production can be contained in the insoluble fraction of the cell lysate; however, this protein has low biological activity and seems to have a different secondary structure [28]. On the other hand, the use of animal cells to produce high quantities of biologically active BDNF has been also reported [30]. However, these methods require special needs for culture and proliferation control reducing the productivity of protein purification.…”

Section: Discussionmentioning

confidence: 99%

Antiapoptotic activity maintenance of Brain Derived Neurotrophic Factor and the C fragment of the tetanus toxin genetic fusion protein

Ciriza¹,

García‐Ojeda

Martín-Burriel³

et al. 2008

Open Life Sciences

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Neurotrophic factors have been widely suggested as a treatment for multiple diseases including motorneuron pathologies, like Amyotrophic Lateral Sclerosis. However, clinical trials in which growth factors have been systematically administered to Amyotrophic Lateral Sclerosis patients have not been effective, owing in part to the short half-life of these factors and their low concentrations at target sites. A possible strategy is the use of the atoxic C fragment of the tetanus toxin as a neurotrophic factor carrier to the motorneurons.The activity of trophic factors should be tested because their genetic fusion to proteins could alter their folding and conformation, thus undermining their neuroprotective properties. For this purpose, in this paper we explored the Brain Derived Neurotrophic Factor (BDNF) activity maintenance after genetic fusion with the C fragment of the tetanus toxin. We demonstrated that BDNF fused with the C fragment of the tetanus toxin induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and maintains its antiapoptotic neuronal activity in Neuro2A cells.

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“…10) In addition, insect cells using a baculovirus expression vector produced BDNF of 150-200 tlg/liter and NT -3 of 300-500 tlg/liter. 13) Though biologically active neurotrophic factors were obtained by animal cell transformants, their cultivation needed careful proliferation control and their productivity was well below that of E. coli.…”

Section: Discussionmentioning

confidence: 99%

Production of Biologically Active Mature Brain-derived Neurotrophic Factor inEscherichia coli

Fukuzono

Fujimori

Shimizu

1995

Bioscience, Biotechnology, and Biochemistry

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Primary Structure and Biological Activity of Human Brain-Derived Neurotrophic Factor

Cited by 75 publications

References 28 publications

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

Antiapoptotic activity maintenance of Brain Derived Neurotrophic Factor and the C fragment of the tetanus toxin genetic fusion protein

Production of Biologically Active Mature Brain-derived Neurotrophic Factor inEscherichia coli

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