title: Dendrobium alkaloids prevent Aβ25-35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice.
abstract: BACKGROUND
  Neuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer's disease (AD). In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA), a Chinese medicinal herb extract, on β-amyloid peptide segment 25-35 (Aβ25-35)-induced neuron and synaptic loss in mice.
  
  
  METHODS
  Aβ25-35(10 µg) was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg) for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex.
  
  
  RESULTS
  DNLA significantly attenuated Aβ25-35-induced spatial learning and memory impairments in mice. DNLA prevented Aβ25-35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex.
  
  
  CONCLUSIONS
  DNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aβ-induced spatial learning and memory impairment in mice.
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Zunyi, Guizhou Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College , Zunyi , Guizhou Province , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College , Zunyi , Guizhou Province , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College , Zunyi , Guizhou Province , China.
authors.forename: Yan-Liu
authors.initials: YL
authors.lastname: Lu
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College , Zunyi , Guizhou Province , China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Li
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Zunyi, Guizhou Province, China.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Shi
keywords: Alzheimer’s disease; Apoptosis; Dendrobium nobile Lindl. alkaloids; Neuron; Neurotrophic factor; Synaptic loss