Histone Deacetylase 1 inhibit primary hippocampal neuron dendritic growth and branching by regulation of neuronal MHC class Ⅰ molecules

Abstract Histone lysine deacetylase (HDACs) inhibitors are widely used as anti-cancer reagents and also as anti-neuropsychiatric reagents. Nonetheless, the cellular functions of different HDACs are found to be diverse and context-dependent from the results obtained from various HDAC inhibitors. Both HDAC1 and HDAC2 are expressed in hippocampal neurons at postnatal stage, but their functions could be overlapping or independently of one other. Major Histocompatibility Complex (MHC) class I molecules play significant roles in the process of establishment and modification of hippocampal synapses. However, the relationship between HDACs and MHC class Ⅰ molecules in the brain has not been reported. In this paper, the expressions of HDAC1 and HDAC2 is found out to be inversely correlated with those of MHC class Ⅰ molecules in the postnatal stages of mice hippocampus. Inhibition of both HDAC1 and HDAC2 by HDACs inhibitors upregulates MHC class Ⅰ molecules expression in primary cultured hippocampal neurons and this could be recapitulated by knockdown of HDAC1 using lentivirus delivery of HDAC1-specific shRNA. Growth and branching of dendrites in cultured hippocampal neurons are reduced by inhibition of HDAC1 and blocking with MHC class Ⅰ antibody can fully rescue the decreased dendritic growth in HDACs inhibitor treated neurons. Our data provide the first evidence that HDAC1 is a regulator that can shape the morphology of hippocampal neurons by modulating MHC class Ⅰ molecules.