Blockade of Astrocytic Calcineurin/NFAT Signaling Helps to Normalize Hippocampal Synaptic Function and Plasticity in a Rat Model of Traumatic Brain Injury.
Jennifer L FurmanPradoldej SompolSusan D KranerMelanie M PleissEsther J PutmanJacob DunkersonHafiz Mohmmad AbdulKelly N RobertsStephen W ScheffChristopher M NorrisPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
Similar to microglia, astrocytes become strongly "activated" with neural damage and exhibit numerous morphologic/biochemical changes, including an increase in the expression/activity of the protein phosphatase calcineurin. Using adeno-associated virus (AAV) to inhibit the calcineurin-dependent activation of the transcription factor NFAT (Nuclear Factor of Activated T cells) selectively, we have shown that activated astrocytes contribute to neural dysfunction in animal models characterized by progressive/chronic neuropathology. Here, we show that the suppression of astrocytic calcineurin/NFATs helps to protect synaptic function and plasticity in an animal model in which pathology arises from a single traumatic brain injury. The findings suggest that at least some astrocyte functions impair recovery after trauma and may provide druggable targets for treating victims of acute nervous system injury.
Keyphrases
- nuclear factor
- traumatic brain injury
- toll like receptor
- transcription factor
- oxidative stress
- poor prognosis
- inflammatory response
- multiple sclerosis
- binding protein
- gene therapy
- liver failure
- immune response
- neuropathic pain
- intensive care unit
- long non coding rna
- small molecule
- cerebral ischemia
- protein protein
- spinal cord
- subarachnoid hemorrhage
- dna binding
- mechanical ventilation