title: Brain-derived Neurotrophic Factor Signaling Pathway: Modulation by Acupuncture in Telomerase Knockout Mice.
abstract: BACKGROUND
  Telomerase is a critical enzyme that is involved in aging and cancer and that is thought to be a part of multiple neurological diseases.
  
  
  OBJECTIVE
  To investigate the telomerase response in the brain to acupuncture, the study examined the levels of expression of brain-derived neurotrophic factor (BDNF) and its downstream signaling molecules, including tyrosine kinase receptor Β (TrkB), p75 neurotrophin receptor (p75NTR), protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK1/2), and nuclear factor κΒ (NF-κΒ).
  
  
  METHODS
  Both telomerase-deficient (Terc⁻/⁻) mice (Terc⁻/⁻ group) and normal, wild-type (WT) mice (WT group) were randomly assigned to 1 of 3 subgroups, 1 receiving acupuncture (acupuncture subgroup), 1 receiving sham acupuncture therapy (sham subgroup), and 1 receiving no treatment (control subgroup).
  
  
  METHODS
  The study occurred at the University of South Florida Health Byrd Alzheimer's Institute (Tampa, FL, USA).
  
  
  METHODS
  The 2 acupuncture subgroups received acupuncture at the stomach 36 (ST-36) position for 30 min/d for 4 d. For the 2 sham groups, the sham point was set at a location approximately 3 mm to the lateral side of the tail on the gluteus muscle following the same schedule.
  
  
  METHODS
  After 4 d, the mice were sacrificed, and the brain tissues were collected. The protein levels in the hippocampus and dentate gyrus (DG) of each mouse were determined by western blotting and immunostaining assays.
  
  
  RESULTS
  The Terc⁻/⁻ group showed downregulated hippocampal BDNF expression compared with the WT mice. Acupuncture at ST-36 for 4 d upregulated BDNF, TrkB, p75NTR, Akt, and ERK1/2 in the DG and hippocampus of the telomerase-deficient mice, but that result was not seen in the WT mice with normally functioning telomerase.
  
  
  CONCLUSIONS
  The use of acupuncture in pathologies associated with telomerase deficiencies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), may provide some benefit in terms of eliciting better clinical responses. The research team believes that result occurs through the activation of BDNF and its downstream signaling pathways in populations of patients who exhibit low telomerase activity.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lin
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Zhi-Xu
authors.initials: ZX
authors.lastname: He
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
mesh_terms: D015670:Acupuncture Therapy / Q000379:methods*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000378:metabolism*; D011897:Random Allocation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C422952:telomerase RNA; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D019098:Telomerase