PMID- 28264667 OWN - NLM STAT- MEDLINE DCOM- 20170915 LR - 20240324 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 18 IP - 1 DP - 2017 Mar 7 TI - Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze. PG - 29 LID - 10.1186/s12868-017-0345-4 [doi] LID - 29 AB - BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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. FAU - Jeong, Da Un AU - Jeong DU AD - Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Lee, Jihyeon AU - Lee J AD - Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. FAU - Chang, Won Seok AU - Chang WS AD - Department of Neurosurgery, Yonsei University College of Medicine, CPO Box 8044, Seoul, Korea. FAU - Chang, Jin Woo AU - Chang JW AD - Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. jchang@yuhs.ac. AD - Department of Neurosurgery, Yonsei University College of Medicine, CPO Box 8044, Seoul, Korea. jchang@yuhs.ac. LA - eng PT - Journal Article DEP - 20170307 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (192 IgG-saporin) RN - 0 (Antibodies, Monoclonal) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cholinergic Agents) RN - 0 (Ribosome Inactivating Proteins, Type 1) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) RN - EC 3.2.2.22 (Saporins) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 1) RN - EC 4.1.1.15 (glutamate decarboxylase 2) SB - IM MH - Animals MH - Antibodies, Monoclonal/administration & dosage MH - Brain-Derived Neurotrophic Factor/metabolism MH - Choline O-Acetyltransferase/metabolism MH - Cholinergic Agents/administration & dosage MH - Cholinergic Neurons/drug effects/metabolism MH - Deep Brain Stimulation/*methods MH - Glutamate Decarboxylase/metabolism MH - Male MH - Maze Learning/*physiology MH - Neurogenesis MH - Rats MH - Rats, Sprague-Dawley MH - Ribosome Inactivating Proteins, Type 1/administration & dosage MH - Saporins MH - Septal Nuclei/drug effects/metabolism/*physiology MH - Spatial Memory/*physiology PMC - PMC5340020 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Deep brain stimulation OT - Spatial memory EDAT- 2017/03/08 06:00 MHDA- 2017/09/16 06:00 PMCR- 2017/03/07 CRDT- 2017/03/08 06:00 PHST- 2016/05/16 00:00 [received] PHST- 2017/02/16 00:00 [accepted] PHST- 2017/03/08 06:00 [entrez] PHST- 2017/03/08 06:00 [pubmed] PHST- 2017/09/16 06:00 [medline] PHST- 2017/03/07 00:00 [pmc-release] AID - 10.1186/s12868-017-0345-4 [pii] AID - 345 [pii] AID - 10.1186/s12868-017-0345-4 [doi] PST - epublish SO - BMC Neurosci. 2017 Mar 7;18(1):29. doi: 10.1186/s12868-017-0345-4.