The effects of BDNF Knockdown on Neuroinflammation in the Male and Female rat brain

Since Brain-Derived Neurotrophic Factor’s (BDNF) discovery in 1982, we know that it plays a critical role in both cell survival and cell death within the central nervous system (CNS). It has been established that BDNF, serves as a regulatory body in the CNS, from development to adulthood by promoting neuronal health, survival, and maintenance. However, little is known about BDNF’s role in the pathogenesis of neurological, neurodegenerative, and neuropsychiatric disorders. Therefore, in this study, we used western blots analysis, to examine the effects of global BDNF knockdown on the protein expression of multiple inflammasome and glial cell markers in healthy male and female rat brains. We hypothesize that BDNF heterozygous rats (BDNF+/- KD), will have altered protein expression of inflammatory markers due to BDNF loss, and that this may occur in a sex specific manner. To test this hypothesis, we examined the activation of the NLRP3 inflammasome pathway in male and female rat hippocampal tissue. When compared to wildtype (WT) controls, only BDNF+/- KD males showed a significant increased protein level expression of reactive oxygen species (TXNIP), and inflammasome marker Caspase-1. When taken together, all four inflammasome markers (NLRP3, ASC, Caspase-1, IL1-β) showed a visual pattern of increase only in the male hippocampi (HPC) and not in the females after BDNF+/- KD. In conclusion our results compel us to believe that BDNF reduction leads to priming of the inflammation in the brain and not a full-blown inflammatory state. This is observed in a sex specific manner, with effects seen only in the male HPC. These findings contribute information about BDNF’s involvement in neuroinflammation and will aid in the development of more effective treatment options for neurodegenerative, and neuropsychiatric disorders in the future.