PMID- 21044172
OWN - NLM
STAT- MEDLINE
DCOM- 20110223
LR  - 20131121
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 32
IP  - 9
DP  - 2010 Nov
TI  - Differential effects of short- and long-term hyperhomocysteinaemia on cholinergic 
      neurons, spatial memory and microbleedings in vivo in rats.
PG  - 1516-27
LID - 10.1111/j.1460-9568.2010.07434.x [doi]
AB  - Hyperhomocysteinaemia (HHcy) has been identified as a cardiovascular risk factor 
      for neurodegenerative brain diseases. The aim of the present study was to 
      investigate the effects of short (5 months) or long (15 months) HHcy in 
      Sprague-Dawley rats in vivo. Short- and long-term HHcy differentially affected 
      spatial memory as tested in a partially baited eight-arm radial maze. HHcy 
      significantly reduced the number of choline acetyltransferase (ChAT)-positive 
      neurons in the basal nucleus of Meynert and ChAT-positive axons in the cortex 
      only after short-term but not long-term treatment, while acetylcholine levels in 
      the cortex were decreased at both time points. Nerve growth factor (NGF) was 
      significantly enhanced in the cortex only after 15 months of HHcy. HHcy did not 
      affect cortical levels of amyloid precursor protein, beta-amyloid(1-42), tau and 
      phospho-tau181 and several inflammatory markers, as well as vascular RECA-1 and 
      laminin density. However, HHcy induced cortical microbleedings, as illustrated by 
      intensive anti-rat IgG-positive spots in the cortex. In order to study the 
      regulation of the key enzyme ChAT, organotypic rat brain slices were incubated 
      with homocysteine, which induced a decline of ChAT that was counteracted by NGF 
      treatment. In conclusion, our data demonstrate that chronic short- and long-term 
      HHcy differentially caused memory impairment, cholinergic dysfunction, NGF 
      expression and vascular microbleedings.
FAU - Pirchl, Michael
AU  - Pirchl M
AD  - Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of 
      Psychiatry and Psychotherapy, Innsbruck Medical, University, Anichstr. 35, A-6020 
      Innsbruck, Austria.
FAU - Ullrich, Celine
AU  - Ullrich C
FAU - Humpel, Christian
AU  - Humpel C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Nerve Growth Factors)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*metabolism
MH  - Animals
MH  - Basal Nucleus of Meynert/metabolism
MH  - Behavior, Animal
MH  - Blood-Brain Barrier/physiology
MH  - Cerebral Cortex/metabolism/pathology
MH  - Cerebrovascular Circulation
MH  - Choline O-Acetyltransferase/metabolism
MH  - Hemorrhage/*physiopathology
MH  - Hyperhomocysteinemia/*physiopathology
MH  - Learning/physiology
MH  - Male
MH  - Memory/*physiology
MH  - Nerve Growth Factors/metabolism
MH  - Neurons/*metabolism
MH  - Neuropsychological Tests
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Culture Techniques
EDAT- 2010/11/04 06:00
MHDA- 2011/02/24 06:00
CRDT- 2010/11/04 06:00
PHST- 2010/11/04 06:00 [entrez]
PHST- 2010/11/04 06:00 [pubmed]
PHST- 2011/02/24 06:00 [medline]
AID - 10.1111/j.1460-9568.2010.07434.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2010 Nov;32(9):1516-27. doi: 10.1111/j.1460-9568.2010.07434.x.