PMID- 23152192
OWN - NLM
STAT- MEDLINE
DCOM- 20130530
LR  - 20231213
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 91
IP  - 2
DP  - 2013 Feb
TI  - Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and 
      ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.
PG  - 167-77
LID - 10.1002/jnr.23142 [doi]
AB  - Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic 
      system, and basal forebrain, accompanied by accumulation of amyloid-beta and tangle 
      formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, 
      is reported to improve cognition and activities of daily living in patients with 
      AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) 
      mice overexpressing the human amyloid precursor protein (hAPP). The 
      neuroprotective effects of CBL may involve multiple mechanisms, including 
      signaling regulation, control of APP metabolism, and expression of neurotrophic 
      factors. We investigate the effects of CBL in the hAPP tg model of AD on levels 
      of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, 
      brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary 
      neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of 
      pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated 
      hAPP tg mice showed levels of pro-NGF comparable to control and increased levels 
      of mature NGF. Consistently with these results, immunohistochemical analysis 
      demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated 
      hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, 
      NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were 
      also unchanged. Analysis of neurotrophin receptors showed preservation of the 
      levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. 
      Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP 
      tg mice, and treatment with CBL reduced these cholinergic deficits. These results 
      suggest that the neurotrophic effects of CBL might involve modulation of the 
      pro-NGF/NGF balance and a concomitant protection of cholinergic neurons.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Ubhi, Kiren
AU  - Ubhi K
AD  - Department of Neurosciences, University of California San Diego, La Jolla, 
      California 92093-0624, USA.
FAU - Rockenstein, Edward
AU  - Rockenstein E
FAU - Vazquez-Roque, Ruben
AU  - Vazquez-Roque R
FAU - Mante, Michael
AU  - Mante M
FAU - Inglis, Chandra
AU  - Inglis C
FAU - Patrick, Christina
AU  - Patrick C
FAU - Adame, Anthony
AU  - Adame A
FAU - Fahnestock, Margaret
AU  - Fahnestock M
FAU - Doppler, Edith
AU  - Doppler E
FAU - Novak, Philip
AU  - Novak P
FAU - Moessler, Herbert
AU  - Moessler H
FAU - Masliah, Eliezer
AU  - Masliah E
LA  - eng
GR  - AG05131/AG/NIA NIH HHS/United States
GR  - P50 AG005131/AG/NIA NIH HHS/United States
GR  - P30 NS076411/NS/NINDS NIH HHS/United States
GR  - P01 AG031097/AG/NIA NIH HHS/United States
GR  - P01 AG022074/AG/NIA NIH HHS/United States
GR  - R37 AG018440/AG/NIA NIH HHS/United States
GR  - P01 AG010435/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121114
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Amino Acids)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Cholinergic Agents)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Ngfr protein, mouse)
RN  - 37KZM6S21G (cerebrolysin)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/genetics/metabolism
MH  - Amino Acids/*therapeutic use
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Choline O-Acetyltransferase/metabolism
MH  - Cholinergic Agents/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation/genetics
MH  - Nerve Growth Factors/genetics/*metabolism
MH  - Neuroprotective Agents/*therapeutic use
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkA/metabolism
MH  - Receptors, Nerve Growth Factor/metabolism
EDAT- 2012/11/16 06:00
MHDA- 2013/06/01 06:00
CRDT- 2012/11/16 06:00
PHST- 2012/04/08 00:00 [received]
PHST- 2012/08/19 00:00 [revised]
PHST- 2012/08/21 00:00 [accepted]
PHST- 2012/11/16 06:00 [entrez]
PHST- 2012/11/16 06:00 [pubmed]
PHST- 2013/06/01 06:00 [medline]
AID - 10.1002/jnr.23142 [doi]
PST - ppublish
SO  - J Neurosci Res. 2013 Feb;91(2):167-77. doi: 10.1002/jnr.23142. Epub 2012 Nov 14.