Age-dependent neuron loss is associated with impaired adult neurogenesis in forebrain neuron-specific Dicer conditional knockout mice

Impairment in the microRNA (miRNA) network causes a number of neurodegenerative diseases. Endoribonuclease Dicer is a key RNase to produce mature miRNAs. It has been shown that Dicer is important for the maintenance of excitatory neuron survival during early postnatal period. However, the role of Dicer in adult mature excitatory neuron survival is not clear. In this study, we generated a mouse model in which Dicer is conditionally inactivated in forebrain excitatory neurons from a mature stage, and this line is termed Dicer conditional knockout (cKO). Significant age-dependent neurodegeneration was observed in the cortex of Dicer cKO mice, indicating an important role of Dicer in the maintenance of mature excitatory neuron survival in the adult cortex. Impairment in adult neurogenesis was found in 6-month but not in young Dicer cKO mice. However, astrocytosis was detected in young Dicer cKO mice displaying no apparent neuron loss. Overall, neurogenesis impairment and neuroinflammation may play pivotal roles in the progression of neurodegeneration.