Sulforaphane increases BDNF expression via HDAC inhibition in primary cortical neurons and 3xTg-AD mice

Abstract

Brains of patients with Alzheimers disease (AD) contain abnormally low levels of brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates learning and memory and promotes the survival of injured neurons. As recent studies indicate that sulforaphane improves learning and memory in animal models, I hypothesized that sulforaphane influences synaptic activity by regulating BDNF levels. I found that sulforaphane treatment increased BDNF levels in mouse primary cortical neurons and restored frontal cortex levels of BDNF in a triple-transgenic mouse model of AD. Also, sulforaphane inhibited histone deacetylase (HDAC) and increased acetylation of histone 3 and 4, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition. Furthermore, sulforaphane increased levels of several BDNF pathway components, including tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), Ca2+/calmodulin-dependent protein kinase II (CaMKII), extracellular signal-regulated kinase (ERK), and Akt, as well as neuronal and synaptic molecules such as microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density protein-95 (PSD-95). These findings suggest that sulforaphane could be used to prevent or treat AD.