Cerebral aquaporin-4 expression is independent of seizures in tuberous sclerosis complex
| Autor: | Hannah Harmsen, Robert P. Carson, Cary Fu, Matthew M. Pearson, Bo Zhang, Brittany P. Short, Robert P. Naftel, Kevin C. Ess, Lindsay K. Kozek, Michael Wong |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities Adolescent Mouse Biology lcsh:RC321-571 03 medical and health sciences Tuberous sclerosis Epilepsy Mice 0302 clinical medicine Seizures Tuberous Sclerosis hemic and lymphatic diseases medicine Animals Humans Child neoplasms lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Aquaporin 4 Cerebral Cortex Mice Knockout Infant Newborn Human brain Middle Aged medicine.disease nervous system diseases 030104 developmental biology medicine.anatomical_structure Neurology Gliosis Tuberous sclerosis complex Astrocytes Child Preschool Female TSC1 sense organs TSC2 medicine.symptom Neuroscience Aquaporin-4 030217 neurology & neurosurgery Astrocyte |
| Zdroj: | Neurobiology of Disease, Vol 129, Iss, Pp 93-101 (2019) |
| Popis: | Astrocytes serve many functions in the human brain, many of which focus on maintenance of homeostasis. Astrocyte dysfunction in Tuberous Sclerosis Complex (TSC) has long been appreciated with activation of the mTORC1 signaling pathway resulting in gliosis and possibly contributing to the very frequent phenotype of epilepsy. We hypothesized that aberrant expression of the astrocyte protein aquaporin-4 (AQP4) may be present in TSC and contribute to disease pathology. Characterization of AQP4 expression in epileptic cortex from TSC patients demonstrated a diffuse increase in AQP4. To determine if this was due to exposure to seizures, we examined Aqp4 expression in mouse models of TSC in which Tsc1 or Tsc2 inactivation was targeted to astrocytes or glial progenitors, respectively. Loss of either Tsc1 or Tsc2 from astrocytes resulted in a marked increase in Aqp4 expression which was sensitive to mTORC1 inhibition with rapamycin. Our findings in both TSC epileptogenic cortex and in a variety of astrocyte culture models demonstrate for the first time that AQP4 expression is dysregulated in TSC. The extent to which AQP4 contributes to epilepsy in TSC is not known, though the similarities in AQP4 expression between TSC and temporal lobe epilepsy supports further studies targeting AQP4 in TSC. |
| Databáze: | OpenAIRE |
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