PMID- 26321354
OWN - NLM
STAT- MEDLINE
DCOM- 20160624
LR  - 20220316
IS  - 1876-4754 (Electronic)
IS  - 1876-4754 (Linking)
VI  - 8
IP  - 6
DP  - 2015 Nov-Dec
TI  - Rapid Modulation of Protein Expression in the Rat Hippocampus Following Deep 
      Brain Stimulation of the Fornix.
PG  - 1058-64
LID - S1935-861X(15)01089-X [pii]
LID - 10.1016/j.brs.2015.07.044 [doi]
AB  - BACKGROUND: The forniceal area is currently being evaluated as a target for deep 
      brain stimulation (DBS) to improve cognitive function in patients with 
      Alzheimer's disease. The molecular changes at downstream targets within the 
      stimulated circuit are unknown. OBJECTIVE: To analyze the modulation of 
      hippocampal protein expression following 1 h of fornix DBS in the rat. METHODS: 
      Animals underwent bilateral forniceal DBS for 1 h and sacrificed at different 
      time-points after the initiation of the stimulation (1 h, 2.5 h, 5 h, 25 h). 
      Bilateral hippocampi were isolated for western blot analyses. RESULTS: Forniceal 
      DBS led to a dramatic elevation of cFos post-stimulation, suggesting that 
      forniceal DBS activates the hippocampus. There was also a significant increase in 
      candidate proteins including several trophic factors, such as brain derived 
      neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) but not 
      glial cell-derived neurotrophic factor (GDNF). There was in addition, increased 
      expression of the synaptic markers growth associated protein 43 (GAP-43), 
      synaptophysin and alpha-synuclein. No changes were observed at the studied 
      time-points in Alzheimer's-related proteins including amyloid precursor protein 
      (APP), tau, phosphorylated tau (ptau), or selected chaperone proteins (HSP40, 
      HSP70 and CHIP). CONCLUSIONS: Forniceal DBS triggers hippocampal activity and 
      rapidly modulate the expression of neurotrophic factors and markers of synaptic 
      plasticity known to play key roles in memory processing. The clinical effects of 
      DBS of the fornix may, in part, be mediated by producing changes in the 
      expression of these proteins.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Gondard, Elise
AU  - Gondard E
AD  - Toronto Western Research Institute, Krembil Discovery Tower, University Health 
      Network, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada.
FAU - Chau, Hien N
AU  - Chau HN
AD  - Toronto Western Research Institute, Krembil Discovery Tower, University Health 
      Network, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada.
FAU - Mann, Amandeep
AU  - Mann A
AD  - Toronto Western Research Institute, Krembil Discovery Tower, University Health 
      Network, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada.
FAU - Tierney, Travis S
AU  - Tierney TS
AD  - Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, 
      MA 02115, USA.
FAU - Hamani, Clement
AU  - Hamani C
AD  - Research Imaging Centre, Centre for Addiction and Mental Health, 250 College 
      Street, Toronto, ON, M5T 1R8, Canada; Campbell Family Mental Health Research 
      Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, 
      ON, M5T 1R8, Canada; Division of Neurosurgery, Department of Surgery, Toronto 
      Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON, M5T 
      2S8, Canada.
FAU - Kalia, Suneil K
AU  - Kalia SK
AD  - Toronto Western Research Institute, Krembil Discovery Tower, University Health 
      Network, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada; Division of 
      Neurosurgery, Department of Surgery, Toronto Western Hospital, University of 
      Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
FAU - Lozano, Andres M
AU  - Lozano AM
AD  - Toronto Western Research Institute, Krembil Discovery Tower, University Health 
      Network, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada; Division of 
      Neurosurgery, Department of Surgery, Toronto Western Hospital, University of 
      Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. Electronic address: 
      lozano@uhnresearch.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150806
PL  - United States
TA  - Brain Stimul
JT  - Brain stimulation
JID - 101465726
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cognition/physiology
MH  - Deep Brain Stimulation/*methods
MH  - Fornix, Brain/*metabolism
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Nerve Growth Factors/*biosynthesis
MH  - Neuronal Plasticity/physiology
MH  - Protein Biosynthesis/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
MH  - Vascular Endothelial Growth Factor A/biosynthesis
OTO - NOTNLM
OT  - Deep brain stimulation
OT  - Fornix
OT  - Hippocampus
OT  - Neurotrophic factors
OT  - Synaptic plasticity
OT  - cFos
EDAT- 2015/09/01 06:00
MHDA- 2016/06/25 06:00
CRDT- 2015/09/01 06:00
PHST- 2015/04/28 00:00 [received]
PHST- 2015/07/24 00:00 [revised]
PHST- 2015/07/29 00:00 [accepted]
PHST- 2015/09/01 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/06/25 06:00 [medline]
AID - S1935-861X(15)01089-X [pii]
AID - 10.1016/j.brs.2015.07.044 [doi]
PST - ppublish
SO  - Brain Stimul. 2015 Nov-Dec;8(6):1058-64. doi: 10.1016/j.brs.2015.07.044. Epub 
      2015 Aug 6.