Alpha-MSH rescues neurons from excitotoxic cell death.
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.
Forslin Aronsson
Asa
A
Division of Neurodegeneration and Neuroinflammation, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
Spulber
Stefan
S
Oprica
Mircea
M
Winblad
Bengt
B
Post
Claes
C
Schultzberg
Marianne
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001831:Body Temperature; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D000521:alpha-MSH; D007608:Kainic Acid