Inhibition of RhoA Activity Does Not Rescue Synaptic Development Abnormalities and Long-Term Cognitive Impairment After Sevoflurane Exposure
| Autor: | Zeqi Huang, Wujian Huang, Yafang Liu, Zhaoxia Liao, Yujuan Li, Junhua Li, Liping Miao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
rho GTP-Binding Proteins 0301 basic medicine medicine.medical_specialty RHOA Dendritic spine Pyridines Dendritic Spines Long-Term Potentiation Synaptogenesis Hippocampus Apoptosis Hippocampal formation Biochemistry Rats Sprague-Dawley Sevoflurane 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Pregnancy Internal medicine medicine Animals Cognitive Dysfunction Enzyme Inhibitors rho-Associated Kinases biology Chemistry Long-term potentiation General Medicine Amides Enzyme Activation 030104 developmental biology Endocrinology Animals Newborn Anesthetics Inhalation Synapses biology.protein Synaptophysin Female Collapsin response mediator protein family Open Field Test 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neurochemical Research. 46:468-481 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/s11064-020-03180-2 |
| Popis: | General anesthetics interfere with dendritic development and synaptogenesis, resulting in cognitive impairment in the developing animals. RhoA signal pathway plays important roles in dendritic development by regulating cytoskeleton protein such as tubulin and actin. However, it's not clear whether RhoA pathway is involved in inhaled general anesthetics sevoflurane-induced synaptic development abnormalities and long-term cognitive dysfunction. Rats at postnatal day 7 (PND7) were injected intraperitoneally with RhoA pathway inhibitor Y27632 or saline 20 min before exposed to 2.8% sevoflurane for 4 h. The apoptosis-related proteins and RhoA/CRMP2 pathway proteins in the hippocampus were measured 6 h after sevoflurane exposure. Cognitive functions were evaluated by the open field test on PND25 rats and contextual fear conditioning test on PND32-33 rats. The dendritic morphology and density of dendritic spines in the pyramidal neurons of hippocampus were determined by Golgi staining and the synaptic plasticity-related proteins were also measured on PND33 rats. Long term potentiation (LTP) from hippocampal slices was recorded on PND34-37 rats. Sevoflurane induced caspase-3 activation, decreased the ratio of Bcl-2/Bax and increased TUNEL-positive neurons in hippocampus of PND7 rats, which were attenuated by inhibition of RhoA. However, sevoflurane had no significant effects on activity of RhoA/CRMP2 pathway. Sevoflurane disturbed dendritic morphogenesis, reduced the number of dendritic spines, decreased proteins expression of PSD-95, drebrin and synaptophysin, inhibited LTP in hippocampal slices and impaired memory ability in the adolescent rats, while inhibition of RhoA activity did not rescue the changes above induced by sevoflurane. RhoA signal pathway did not participate in sevoflurane-induced dendritic and synaptic development abnormalities and cognitive dysfunction in developing rats. |
| Databáze: | OpenAIRE |
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