Neuroprotective effects of artemisinin against isoflurane-induced cognitive impairments and neuronal cell death involve JNK/ERK1/2 signalling and improved hippocampal histone acetylation in neonatal rats
| Autor: | Guang Xu, Ping-le Li, Hai-Ming Guo, Xueping Han, Yun-Li Huang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Programmed cell death MAP Kinase Signaling System Pharmaceutical Science Morris water navigation task Apoptosis Pharmacology Biology Neuroprotection Hippocampus Histones Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Pregnancy Survivin medicine Animals Cognitive Dysfunction Artemisinin Maze Learning Neurons Cell Death Isoflurane Acetylation Artemisinins XIAP Rats 030104 developmental biology Neuroprotective Agents Animals Newborn Female 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | The Journal of pharmacy and pharmacology. 69(6) |
| ISSN: | 2042-7158 |
| Popis: | Objective This study was performed to assess the effect of artemisinin against isoflurane-induced neuronal apoptosis and cognitive impairment in neonatal rats. Methods Artemisinin (50, 100 or 200 mg/kg b.wt/day; oral gavage) was administered to separate groups of neonatal rats starting from postnatal day 3 (P3) to postnatal day 21 (P21). On postnatal day 7 (P7), animals were exposed to inhalation anaesthetic isoflurane (0.75%) for 6 h. Key findings Neuronal apoptosis following anaesthetic exposure was significantly reduced by artemisinin. Isoflurane-induced upregulated cleaved caspase-3, Bax and Bad expression were downregulated. Western blotting analysis revealed that treatment with artemisinin significantly enhanced the expression of anti-apoptotic proteins (Bcl-2, Bcl-xL, c-IAP-1, c-IAP-2, xIAP and survivin). Artemisinin increased the acetylation of H3K9 and H4K12 while reducing the expression of histone deacetlyases (HDACs) – HDAC-2 and HDAC-3. Isoflurane-induced activation of JNK signalling and downregulated ERK1/2 expression was effectively modulated by artemisinin. General behaviour of the animals in open-field and T-maze test were improved. Morris water maze test and object recognition test revealed better learning, working memory and also better memory retention on artemisinin treatment. Conclusions Artemisinin effectively inhibited neuronal apoptosis and improved cognition and memory via regulating histone acetylation and JNK/ERK1/2 signalling. |
| Databáze: | OpenAIRE |
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