PMID- 12478619
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20151119
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 71
IP  - 1
DP  - 2003 Jan 1
TI  - Effects of tumor necrosis factor-alpha central administration on hippocampal 
      damage in rat induced by amyloid beta-peptide (25-35).
PG  - 110-20
AB  - Male Wistar rats received unilateral intrahippocampal injections of 3 nmol (3.18 
      microg) aggregated Abeta(25-35), intracerebroventricular bilateral injections of 
      0.5 microg human recombinant TNFalpha or both (Abeta(25-35) + TNFalpha-treated 
      animals). Seven days after the surgery brain sections were stained with cresyl 
      violet (Nissl), for fragmented DNA (TUNEL), glial fibrillar acidic protein (GFAP) 
      and isolectin B4-reactive microglia. In addition, caspase-3 activity in brain 
      regions was measured fluorometrically. The morphology of the hippocampus after 
      the injection of Abeta(25-35) or both Abeta(25-35) and TNFalpha (but not TNFalpha 
      alone) showed cell loss in the CA1 pyramidal cell layer. The extension of 
      neuronal degeneration measured in the CA1 field was significantly larger in 
      Abeta(25-35)-treated groups compared to the contralateral hemisphere of both 
      vehicle-treated controls and animals injected with TNFalpha alone. TNFalpha 
      augmented the Abeta(25-35)-induced damage, significantly increasing the extension 
      of degenerating area. Administration of Abeta(25-35) caused reactive gliosis in 
      the ipsilateral hemisphere as demonstrated by upregulation of GFAP expression and 
      the presence of hypertrophic astrocytes in the hippocampus. This effect was much 
      more prominent in the hippocampi of rats treated with Abeta(25-35) + TNFalpha but 
      absent after administration of TNFalpha alone. In both Abeta(25-35)-treated 
      groups, the damaged area of the hippocampal CA1 field and lateral band of dentate 
      gyrus displayed many darkly stained round isolectin B4-positive phagocyte-like 
      microglial cells. Sparse TUNEL-positive nuclei were found in the hippocampi of 
      rats treated with Abeta(25-35) alone or together with TNFalpha, but not in the 
      control brain sections or in brain sections of TNFalpha-injected animals. The 
      activity of caspase-3 increased significantly in the ipsilateral hippocampus 
      after the injection of Abeta(25-35). Surprisingly, administration of TNFalpha 
      into the cerebral ventricles prevented this Abeta(25-35)-induced increase in 
      hippocampal caspase-3 activity. The results are discussed from the perspective of 
      dual (neuroprotective and neurodestructive) roles of TNF in the brain.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Stepanichev, Mikhail Yu
AU  - Stepanichev MY
AD  - Department of Functional Biochemistry of the Nervous System, Institute of Higher 
      Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, 
      Russia.
FAU - Zdobnova, Irina M
AU  - Zdobnova IM
FAU - Yakovlev, Alexander A
AU  - Yakovlev AA
FAU - Onufriev, Mikhail V
AU  - Onufriev MV
FAU - Lazareva, Natalia A
AU  - Lazareva NA
FAU - Zarubenko, Irina I
AU  - Zarubenko II
FAU - Gulyaeva, Natalia V
AU  - Gulyaeva NV
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (CFLAR protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lectins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (amyloid beta-protein (35-25))
SB  - IM
MH  - Amyloid beta-Peptides/*physiology/toxicity
MH  - Animals
MH  - Astrocytes
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein
MH  - Carrier Proteins/drug effects/metabolism
MH  - Cell Death/drug effects
MH  - Cerebral Cortex/drug effects/pathology
MH  - Disease Models, Animal
MH  - Drug Interactions
MH  - Functional Laterality
MH  - Glial Fibrillary Acidic Protein/drug effects/metabolism
MH  - Gliosis/chemically induced/*prevention & control
MH  - Hippocampus/*injuries/pathology
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Injections, Intraventricular
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Lectins
MH  - Male
MH  - Microglia/metabolism
MH  - Nerve Degeneration
MH  - Peptide Fragments/*physiology/toxicity
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Fusion Proteins/therapeutic use
MH  - Tumor Necrosis Factor-alpha/*therapeutic use
EDAT- 2002/12/13 04:00
MHDA- 2003/03/13 04:00
CRDT- 2002/12/13 04:00
PHST- 2002/12/13 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2002/12/13 04:00 [entrez]
AID - 10.1002/jnr.10469 [doi]
PST - ppublish
SO  - J Neurosci Res. 2003 Jan 1;71(1):110-20. doi: 10.1002/jnr.10469.