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Published on: June 26, 2018
Alpha-MSH rescues neurons from excitotoxic cell death
Asa Forslin Aronsson1, Stefan Spulber, Mircea Oprica
1Division of Neurodegeneration and Neuroinflammation, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
Abstract:
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.
Insights
Alpha-melanocyte-stimulating hormone (alpha-MSH) protects against neurodegeneration. This study shows alpha-MSH treatment significantly increases neuron survival following kainic acid-induced excitotoxicity in rats.
Area of Science:
- Neuroscience
- Neuroprotection
- Neuroinflammation
Background:
- Kainic acid (KA) induces excitotoxic damage in the rat brain, leading to neurodegeneration and gliosis.
- Pro-inflammatory cytokines and changes in neurotrophic factors like BDNF are implicated in excitotoxic insults.
Purpose of the Study:
- To investigate the neuroprotective effects of alpha-melanocyte-stimulating hormone (alpha-MSH) against KA-induced excitotoxicity.
- To examine the impact of alpha-MSH on neurodegeneration, gliosis, BDNF levels, and pro-inflammatory cytokines.
Main Methods:
- Male Sprague-Dawley rats received KA (i.p.) to induce excitotoxicity.
- alpha-MSH was administered intraperitoneally at 20 min, 24 h, and 48 h post-KA.
- Neuronal viability, gliosis, BDNF, and cytokine levels (IL-1beta, IL-6, TNF-alpha) were assessed at various time points.
Main Results:
- KA administration significantly reduced neuronal viability in the CA1 pyramidal cell layer.
- alpha-MSH treatment markedly increased the number of viable neurons compared to KA alone.
- alpha-MSH reduced astrocyte activation and delayed the increase in IL-1beta levels.
Conclusions:
- alpha-MSH demonstrates significant neuroprotective effects against excitotoxic insults.
- The findings support the hypothesis that alpha-MSH administration can rescue neurons subjected to excitotoxic damage.
- alpha-MSH may offer a therapeutic strategy for conditions involving excitotoxicity and neurodegeneration.
