PMID- 17952633
OWN - NLM
STAT- MEDLINE
DCOM- 20080204
LR  - 20211020
IS  - 0895-8696 (Print)
IS  - 0895-8696 (Linking)
VI  - 33
IP  - 3
DP  - 2007
TI  - Alpha-MSH rescues neurons from excitotoxic cell death.
PG  - 239-51
AB  - This study investigates the effects of alpha-melanocyte-stimulating hormone 
      (alpha-MSH), on neurodegeneration, gliosis and changes in the neurotrophic 
      protein brain-derived neurotrophic factor (BDNF) and in pro-inflammatory 
      cytokines, following kainic acid (KA)-induced excitotoxic damage in the rat. Male 
      Sprague-Dawley rats were treated with alpha-MSH (intraperitoneally, i.p.) at 20 
      min, and 24 and 48 h following administration of 10 mg/kg KA (i.p.). The animals 
      were sacrificed at 30 min, 4 h, 24 h and 72 h after KA-administration and the 
      levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis 
      factor-alpha (TNF-alpha) were analysed in samples of hippocampus and 
      hypothalamus. Levels of BDNF were analysed in the hippocampus. Stereological 
      quantification showed a markedly reduced number of viable neurons in the CA1 
      pyramidal cell layer upon KA-administration as compared to animals injected with 
      vehicle (p < 0.05, 79,587 +/- 25,554 vs. 145,254 +/- 27,871). The number of 
      viable neurons upon administration of alpha-MSH was significantly higher than 
      upon KA alone (p < 0.05, 119,776 +/- 33,158, KA+alpha-MSH vs. 79,587 +/- 27,554, 
      KA + Saline). Astrocyte activation due to the KA-induced excitotoxicity was 
      reduced, and the KA-induced increase in IL-1beta levels was delayed by the 
      treatment with alpha-MSH. In conclusion, the degree of reduction in cell 
      viability in the hippocampus CA1 pyramidal cell layer upon KA-induced 
      excitotoxicity was similar to that seen previously upon global cerebral 
      ischaemia. Furthermore, the administration of alpha-MSH resulted in a similar 
      increase in cell viability, supporting the hypothesis that administration of 
      alpha-MSH has rescuing effects on neurons subjected to excitotoxic insults.
FAU - Forslin Aronsson, Asa
AU  - Forslin Aronsson A
AD  - Division of Neurodegeneration and Neuroinflammation, Department of Neurobiology, 
      Care Sciences and Society, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
FAU - Spulber, Stefan
AU  - Spulber S
FAU - Oprica, Mircea
AU  - Oprica M
FAU - Winblad, Bengt
AU  - Winblad B
FAU - Post, Claes
AU  - Post C
FAU - Schultzberg, Marianne
AU  - Schultzberg M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070417
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Neuroprotective Agents)
RN  - 581-05-5 (alpha-MSH)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/metabolism
MH  - Body Temperature
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - *Cell Death
MH  - Cytokines/metabolism
MH  - Excitatory Amino Acid Agonists/*toxicity
MH  - Hippocampus/cytology/metabolism
MH  - Hypothalamus/cytology/metabolism
MH  - Kainic Acid/*toxicity
MH  - Male
MH  - Neurons/cytology/metabolism
MH  - Neuroprotective Agents/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - alpha-MSH/*metabolism
EDAT- 2007/10/24 09:00
MHDA- 2008/02/05 09:00
CRDT- 2007/10/24 09:00
PHST- 2006/10/06 00:00 [received]
PHST- 2006/10/10 00:00 [accepted]
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2008/02/05 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - 10.1007/s12031-007-0019-2 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2007;33(3):239-51. doi: 10.1007/s12031-007-0019-2. Epub 2007 Apr 
      17.