PMID- 28266222
OWN - NLM
STAT- MEDLINE
DCOM- 20171012
LR  - 20181113
IS  - 1759-0914 (Electronic)
IS  - 1759-0914 (Linking)
VI  - 9
IP  - 2
DP  - 2017 Mar-Apr
TI  - Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor 
      Exacerbates Neuropathology in a Mouse Model of Alzheimer's Disease.
PG  - 1759091417696161
LID - 10.1177/1759091417696161 [doi]
LID - 1759091417696161
AB  - Damage occurring to noradrenergic neurons in the locus coeruleus (LC) contributes 
      to the evolution of neuroinflammation and neurodegeneration in a variety of 
      conditions and diseases. One cause of LC damage may be loss of neurotrophic 
      support from LC target regions. We tested this hypothesis by conditional 
      unilateral knockout of brain-derived neurotrophic factor (BDNF) in adult mice. To 
      evaluate the consequences of BDNF loss in the context of neurodegeneration, the 
      mice harbored familial mutations for human amyloid precursor protein and 
      presenilin-1. In these mice, BDNF depletion reduced tyrosine hydroxylase 
      staining, a marker of noradrenergic neurons, in the rostral LC. BDNF depletion 
      also reduced noradrenergic innervation in the hippocampus, the frontal cortex, 
      and molecular layer of the cerebellum, assessed by staining for dopamine beta 
      hydroxylase. BDNF depletion led to an increase in cortical amyloid plaque numbers 
      and size but was without effect on plaque numbers in the striatum, a site with 
      minimal innervation from the LC. Interestingly, cortical Iba1 staining for 
      microglia was reduced by BDNF depletion and was correlated with reduced dopamine 
      beta hydroxylase staining. These data demonstrate that reduction of BDNF levels 
      in an LC target region can cause retrograde damage to LC neurons, leading to 
      exacerbation of neuropathology in distinct LC target areas. Methods to reduce 
      BDNF loss or supplement BDNF levels may be of value to reduce neurodegenerative 
      processes normally limited by LC noradrenergic activities.
FAU - Braun, David J
AU  - Braun DJ
AD  - 1 Department of Anesthesiology, University of Illinois, Chicago, IL, USA.
FAU - Kalinin, Sergey
AU  - Kalinin S
AD  - 1 Department of Anesthesiology, University of Illinois, Chicago, IL, USA.
FAU - Feinstein, Douglas L
AU  - Feinstein DL
AD  - 2 Jesse Brown VA Medical Center, Chicago, IL, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - ASN Neuro
JT  - ASN neuro
JID - 101507115
RN  - 0 (APP protein, human)
RN  - 0 (Aif1 protein, mouse)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
SB  - IM
MH  - Alzheimer Disease/*metabolism/*pathology
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*deficiency/genetics
MH  - Calcium-Binding Proteins/metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/*metabolism/*pathology
MH  - Humans
MH  - Locus Coeruleus/metabolism/pathology
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microfilament Proteins/metabolism
MH  - Microglia/metabolism/pathology
MH  - Neurons/metabolism/pathology
MH  - Plaque, Amyloid/metabolism/pathology
MH  - Presenilin-1/genetics/metabolism
PMC - PMC5415058
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - adeno-associated virus
OT  - amyloid
OT  - brain-derived neurotrophic factor
OT  - locus coeruleus
OT  - neuroinflammation
OT  - neurotrophin
OT  - noradrenaline
OT  - tyrosine hydroxylase
EDAT- 2017/03/08 06:00
MHDA- 2017/10/13 06:00
PMCR- 2017/03/07
CRDT- 2017/03/08 06:00
PHST- 2017/03/08 06:00 [entrez]
PHST- 2017/03/08 06:00 [pubmed]
PHST- 2017/10/13 06:00 [medline]
PHST- 2017/03/07 00:00 [pmc-release]
AID - 10.1177_1759091417696161 [pii]
AID - 10.1177/1759091417696161 [doi]
PST - ppublish
SO  - ASN Neuro. 2017 Mar-Apr;9(2):1759091417696161. doi: 10.1177/1759091417696161.