PMID- 25555929
OWN - NLM
STAT- MEDLINE
DCOM- 20151029
LR  - 20181113
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 288
DP  - 2015 Mar 12
TI  - Expansion of the dentate mossy fiber-CA3 projection in the brain-derived 
      neurotrophic factor-enriched mouse hippocampus.
PG  - 10-23
LID - S0306-4522(14)01085-9 [pii]
LID - 10.1016/j.neuroscience.2014.12.036 [doi]
AB  - Structural changes that alter hippocampal functional circuitry are implicated in 
      learning impairments, mood disorders and epilepsy. Reorganization of mossy fiber 
      (MF) axons from dentate granule cells is one such form of plasticity. Increased 
      neurotrophin signaling is proposed to underlie MF plasticity, and there is 
      evidence to support a mechanistic role for brain-derived neurotrophic factor 
      (BDNF) in this process. Transgenic mice overexpressing BDNF in the forebrain 
      under the alpha-calcium/calmodulin-dependent protein kinase II promoter (TgBDNF mice) 
      exhibit spatial learning deficits at 2-3months of age, followed by the emergence 
      of spontaneous seizures at  approximately 6months. These behavioral changes suggest that 
      chronic increases in BDNF progressively disrupt hippocampal functional 
      organization. To determine if the dentate MF pathway is structurally altered in 
      this strain, the present study employed Timm staining and design-based stereology 
      to compare MF distribution and projection volumes in transgenic and wild-type 
      mice at 2-3months, and at 6-7months. Mice in the latter age group were assessed 
      for seizure vulnerability with a low dose of pilocarpine given 2h before 
      euthanasia. At 2-3months, TgBDNF mice showed moderate expansion of CA3-projecting 
      MFs ( approximately 20%), with increased volumes measured in the suprapyramidal (SP-MF) and 
      intra/infrapyramidal (IIP-MF) compartments. At 6-7months, a subset of transgenic 
      mice exhibited increased seizure susceptibility, along with an increase in IIP-MF 
      volume ( approximately 30%). No evidence of MF sprouting was seen in the inner molecular layer. 
      Additional stereological analyses demonstrated significant increases in molecular 
      layer (ML) volume in TgBDNF mice at both ages, as well as an increase in granule 
      cell number by 8months of age. Collectively, these results indicate that 
      sustained increases in endogenous BDNF modify dentate structural organization 
      over time, and may thereby contribute to the development of pro-epileptic 
      circuitry.
CI  - Published by Elsevier Ltd.
FAU - Isgor, C
AU  - Isgor C
AD  - Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida 
      Atlantic University, United States.
FAU - Pare, C
AU  - Pare C
AD  - Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida 
      Atlantic University, United States.
FAU - McDole, B
AU  - McDole B
AD  - Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida 
      Atlantic University, United States.
FAU - Coombs, P
AU  - Coombs P
AD  - Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida 
      Atlantic University, United States.
FAU - Guthrie, K
AU  - Guthrie K
AD  - Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida 
      Atlantic University, United States. Electronic address: kguthrie@fau.edu.
LA  - eng
GR  - R15 DC012425/DC/NIDCD NIH HHS/United States
GR  - DC010485/DC/NIDCD NIH HHS/United States
GR  - R15 DC010485/DC/NIDCD NIH HHS/United States
GR  - DC012425/DC/NIDCD NIH HHS/United States
GR  - DA023675/DA/NIDA NIH HHS/United States
GR  - R15 DA023675/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141231
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 01MI4Q9DI3 (Pilocarpine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - CA3 Region, Hippocampal/cytology/*growth & development/metabolism
MH  - Cell Count
MH  - Dentate Gyrus/*growth & development/metabolism
MH  - Female
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurons/cytology/metabolism
MH  - Pilocarpine
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Seizures/metabolism
PMC - PMC4324623
MID - NIHMS652724
OTO - NOTNLM
OT  - TrkB
OT  - brain-derived neurotrophic factor
OT  - dentate granule cells
OT  - epilepsy
OT  - hippocampus
OT  - seizure
COIS- Conflict of interest The authors declare no conflict of interest, financial or 
      otherwise.
EDAT- 2015/01/04 06:00
MHDA- 2015/10/30 06:00
PMCR- 2016/03/12
CRDT- 2015/01/04 06:00
PHST- 2014/06/25 00:00 [received]
PHST- 2014/12/10 00:00 [revised]
PHST- 2014/12/13 00:00 [accepted]
PHST- 2015/01/04 06:00 [entrez]
PHST- 2015/01/04 06:00 [pubmed]
PHST- 2015/10/30 06:00 [medline]
PHST- 2016/03/12 00:00 [pmc-release]
AID - S0306-4522(14)01085-9 [pii]
AID - 10.1016/j.neuroscience.2014.12.036 [doi]
PST - ppublish
SO  - Neuroscience. 2015 Mar 12;288:10-23. doi: 10.1016/j.neuroscience.2014.12.036. 
      Epub 2014 Dec 31.