Altered Neurotrophin Expression in a Mouse Model for Traumatic Brain Injury

Abstract

Neurotrophins are critical signaling molecules for cells of the central nervous system, as they have the ability to regulate proliferation, differentiation, and apoptosis. Neurotrophin expression can be influenced by sensory input, which has implications for both normal development of the central nervous system and remodeling that may occur in response to altered sensory input. We examined neurotrophin expression in the visual cortex in response to retinal degeneration as a model for Traumatic Brain Injury (TBI). We used a well-characterized mouse model system in which loss of function of a visual signaling molecule (phosphodiesterase 6β) causes retinal degeneration and loss of visual acuity in all mice by postnatal day (PND) 49. Using Q-PCR, we showed that expression of several neurotrophins, including BDNF, NT-3, and NGF was altered at the mRNA level in response to retinal degeneration. We also examined the protein expression levels of BDNF and NT-3 using western blotting. These analyses showed a decrease in BDNF protein levels at PND 49 in response to retinal degeneration, consistent with mRNA results; NT-3 protein levels did not reflect mRNA alterations that were seen in response to retinal degeneration, suggesting that NT-3 expression is regulated post-transcriptionally. The alterations in neurotrophin expression could have implications for remodeling in response to the loss of sensory input to the visual cortex, which can be related to TBI.