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RESEARCH PRODUCT
Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression
Carmen Ferrer-pérezKatarzyna Anna DudekCaroline MenardSimon LabrecqueNaguib MechawarSam A. GoldenKatherine B. LeclairScott J. RussoLaurence Dion-albertManon LebelCarol A. TammingaGustavo TureckiEllen TuckEllen Tucksubject
MaleHistone Deacetylase 1InflammationFOXO1Blood–brain barrierNucleus AccumbensEpigenesis GeneticProinflammatory cytokineMice03 medical and health sciences0302 clinical medicinevascularmedicineAnimalsHumansClaudin-5030304 developmental biologyInflammationSocial stressDepressive Disorder Major0303 health sciencesantidepressantMultidisciplinaryDepressionbusiness.industrySystems BiologyBiological Sciencesmedicine.diseasemood disordersAntidepressive Agents3. Good healthMice Inbred C57BLDisease Models Animalmedicine.anatomical_structureMood disordersBlood-Brain BarrierMajor depressive disorderAntidepressantmedicine.symptombusinessNeuroscienceStress Psychologicalepigenetic030217 neurology & neurosurgerySignal Transductiondescription
Significance Thirty to fifty percent of depressed individuals are unresponsive to commonly prescribed antidepressant treatments, suggesting that biological mechanisms, such as stress-induced inflammation and blood vessel dysfunction, remain untreated. The blood–brain barrier is the ultimate frontier between the brain and harmful toxins or inflammatory signals circulating in the blood. Depression and vulnerability to chronic social stress are associated with loss of this barrier integrity; however, the mechanisms involved remain poorly understood. Identification of adaptations leading to resilience under stressful conditions could help develop novel treatments. Here we combined behavioral, pharmacological, and cell-specific gene profiling experiments in mice with epigenetic, molecular, and anatomical analysis of human samples to unravel mechanisms with therapeutic potential to protect the brain and promote resilience.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-01-23 | Proceedings of the National Academy of Sciences |