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Ever since its first use in surgery, general anesthesia has been regarded as a medical miracle enabling countless life-saving diagnostic and therapeutic interventions without pain sensation and traumatic memories. Despite several decades of research, there is a lack of understanding of how general anesthetics induce a reversible coma-like state. Emerging evidence suggests that even brief exposure to general anesthesia may have a lasting impact on mature and especially developing brains. Commonly used anesthetics have been shown to destabilize dendritic spines and induce an enhanced plasticity state, with effects on cognition, motor functions, mood, and social behavior. Herein, we review the effects of the most widely used general anesthetics on dendritic spine dynamics and discuss functional and molecular correlates with action mechanisms. We consider the impact of neurodevelopment, anatomical location of neurons, and their neurochemical profile on neuroplasticity induction, and review the putative signaling pathways. It emerges that in addition to possible adverse effects, the stimulation of synaptic remodeling with the formation of new connections by general anesthetics may present tremendous opportunities for translational research and neurorehabilitation.
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- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2-/- mice we demonstrate that CRMP2 has a moderate effect on Sema3A-dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum. Surprisingly, crmp2-/- mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, which is consistent with impaired Sema3F signaling and with models of autism spectrum disorder (ASD). We demonstrate that CRMP2 mediates Sema3F signaling in primary neurons and that crmp2-/- mice display ASD-related social behavior changes in the early postnatal period as well as in adults. Together, we demonstrate that CRMP2 mediates Sema3F-dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD.
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- dendritické trny MeSH
- membránové proteiny fyziologie MeSH
- mezibuněčné signální peptidy a proteiny genetika MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony MeSH
- neuroplasticita MeSH
- poruchy autistického spektra * MeSH
- proteiny nervové tkáně genetika fyziologie MeSH
- semaforiny * MeSH
- signální transdukce MeSH
- zvířata MeSH
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- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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- dendrity fyziologie ultrastruktura MeSH
- endocytóza MeSH
- hipokampus fyziologie ultrastruktura MeSH
- hladké endoplazmatické retikulum ultrastruktura MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- počítačové zpracování obrazu MeSH
- stárnutí fyziologie MeSH
- synapse ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
The structure of neurons in the central auditory system is vulnerable to various kinds of acoustic exposures during the critical postnatal developmental period. Here we explored long-term effects of exposure to an acoustically enriched environment (AEE) during the third and fourth weeks of the postnatal period in rat pups. AEE consisted of a spectrally and temporally modulated sound of moderate intensity, reinforced by a behavioral paradigm. At the age of 3-6 months, a Golgi-Cox staining was used to evaluate the morphology of neurons in the inferior colliculus (IC), the medial geniculate body (MGB), and the auditory cortex (AC). Compared to controls, rats exposed to AEE showed an increased mean dendritic length and volume and the soma surface in the external cortex and the central nucleus of the IC. The spine density increased in both the ventral and dorsal divisions of the MGB. In the AC, the total length and volume of the basal dendritic segments of pyramidal neurons and the number and density of spines on these dendrites increased significantly. No differences were found on apical dendrites. We also found an elevated number of spines and spine density in non-pyramidal neurons. These results show that exposure to AEE during the critical developmental period can induce permanent changes in the structure of neurons in the central auditory system. These changes represent morphological correlates of the functional plasticity, such as an improvement in frequency tuning and synchronization with temporal parameters of acoustical stimuli.
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- akustická stimulace MeSH
- colliculus inferior cytologie fyziologie MeSH
- dendritické trny fyziologie MeSH
- dendrity fyziologie MeSH
- krysa rodu rattus MeSH
- metathalamus cytologie fyziologie MeSH
- neurony cytologie fyziologie MeSH
- neuroplasticita fyziologie MeSH
- novorozená zvířata MeSH
- potkani Long-Evans MeSH
- sluchová dráha cytologie fyziologie MeSH
- sluchové korové centrum cytologie fyziologie MeSH
- tvar buňky fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In previous studies (Grécová et al., Eur J Neurosci 29:1921-1930, 2009; Bures et al., Eur J Neurosci 32:155-164, 2010), we demonstrated that after an early postnatal short noise exposure (8 min 125 dB, day 14) changes in the frequency tuning curves as well as changes in the coding of sound intensity are present in the inferior colliculus (IC) of adult rats. In this study, we analyze on the basis of the Golgi-Cox method the morphology of neurons in the IC, the medial geniculate body (MGB) and the auditory cortex (AC) of 3-month-old Long-Evans rats exposed to identical noise at postnatal day 14 and compare the results to littermate controls. In rats exposed to noise as pups, the mean total length of the neuronal tree was found to be larger in the external cortex and the central nucleus of the IC and in the ventral division of the MGB. In addition, the numerical density of dendritic spines was decreased on the branches of neurons in the ventral division of the MGB in noise-exposed animals. In the AC, the mean total length of the apical dendritic segments of pyramidal neurons was significantly shorter in noise-exposed rats, however, only slight differences with respect to controls were observed in the length of basal dendrites of pyramidal cells as well as in the neuronal trees of AC non-pyramidal neurons. The numerical density of dendritic spines on the branches of pyramidal AC neurons was lower in exposed rats than in controls. These findings demonstrate that early postnatal short noise exposure can induce permanent changes in the development of neurons in the central auditory system, which apparently represent morphological correlates of functional plasticity.
- MeSH
- akustická stimulace MeSH
- colliculus inferior růst a vývoj patologie MeSH
- dendritické trny patologie MeSH
- hluk škodlivé účinky MeSH
- metathalamus růst a vývoj patologie MeSH
- nervová síť patologie MeSH
- neurony patologie MeSH
- neuroplasticita MeSH
- novorozená zvířata MeSH
- potkani Long-Evans MeSH
- pyramidové buňky patologie MeSH
- sluchová dráha patologie MeSH
- sluchové korové centrum růst a vývoj patologie MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
