title: Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze.
abstract: The possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group.
  
  
  
  The most effective memory restoration occurred in the pre-stimulation group. Moreover, the pre-stimulation group exhibited better recall of the platform position than the other stimulation groups. An increase in the level of brain derived neurotrophic factor (BDNF) was observed in the pre-stimulation group; this increase was maintained for 1 week. However, acetylcholinesterase activity in the pre-stimulation group was not significantly different from the lesion group.
  
  
  
  Memory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Da Un
authors.initials: DU
authors.lastname: Jeong
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jihyeon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Yonsei University College of Medicine, CPO Box 8044, Seoul, Korea.
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. jchang@yuhs.ac.|Department of Neurosurgery, Yonsei University College of Medicine, CPO Box 8044, Seoul, Korea. jchang@yuhs.ac.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000008:administration & dosage; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism; D046690:Deep Brain Stimulation / Q000379:methods*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage; D000076985:Saporins; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology*
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D018678:Cholinergic Agents; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D000076985:Saporins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: Brain-derived neurotrophic factor; Deep brain stimulation; Spatial memory