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Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway
- Source :
- PLoS Biology, PLoS Biology, Vol 15, Iss 7, p e2001246 (2017)
- Publication Year :
- 2016
-
Abstract
- Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.
- Subjects :
- Dendritic spine
QH301-705.5
Dendritic Spines
Hippocampal formation
Biology
Hippocampus
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Mice
0302 clinical medicine
030202 anesthesiology
medicine
Animals
Cognitive Dysfunction
Biology (General)
PI3K/AKT/mTOR pathway
Neurons
General Immunology and Microbiology
Isoflurane
General Neuroscience
Dentate gyrus
TOR Serine-Threonine Kinases
Correction
Environmental exposure
Environmental Exposure
Granule cell
3. Good health
medicine.anatomical_structure
Anesthetic
Anesthetics, Inhalation
General Agricultural and Biological Sciences
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15457885
- Volume :
- 15
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS biology
- Accession number :
- edsair.doi.dedup.....756e2dc3636f5fe4be4a68a8c31b8f35