کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5630544 1580613 2017 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer's disease
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer's disease
چکیده انگلیسی


- BDNF and NGF transcripts exhibit differential dysregulation throughout amyloid pathology progression in APP transgenic rats
- While BDNF mRNA is reduced at early stages, there were no changes in NGF mRNA expression even at advanced time points
- With advanced pathology, deficits in the NGF metabolic pathway were evident, in line with an upregulation of proNGF
- This time point was also accompanied by a downregulation of cortical and hippocampal cholinergic synapses

Evidence from human neuropathological studies indicates that the levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are compromised in Alzheimer's disease. However, the causes and temporal (pathology-dependent) evolution of these alterations are not completely understood. To elucidate these issues, we investigated the McGill-R-Thy1-APP transgenic rat, which exhibits progressive intracellular and extracellular amyloid-beta (Aβ) pathology and ensuing cognitive deficits. Neurochemical analyses revealed a differential dysregulation of NGF and BDNF transcripts and protein expression. While BDNF mRNA levels were significantly reduced at very early stages of amyloid pathology, before plaques appeared, there were no changes in NGF mRNA expression even at advanced stages. Paradoxically, the protein levels of the NGF precursor were increased. These changes in neurotrophin expression are identical to those seen during the progression of Alzheimer's disease. At advanced pathological stages, deficits in the protease cascade controlling the maturation and degradation of NGF were evident in McGill transgenic rats, in line with the paradoxical upregulation of proNGF, as seen in Alzheimer's disease, in the absence of changes in NGF mRNA. The compromise in NGF metabolism and BDNF levels was accompanied by downregulation of cortical cholinergic synapses; strengthening the evidence that neurotrophin dysregulation affects cholinergic synapses and synaptic plasticity. Our findings suggest a differential temporal deregulation of NGF and BDNF neurotrophins, whereby deficits in BDNF mRNA appear at early stages of intraneuronal Aβ pathology, before alterations in NGF metabolism and cholinergic synapse loss manifest.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 108, December 2017, Pages 307-323
نویسندگان
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