Mice unable to synthesize dopamine (DA) specifically in dopaminergic neurons were created by inactivating the tyrosine hydroxylase (TH) gene then by restoring TH function in noradrenergic cells. These DA-deficient (DA-/-) mice were born at expected frequency but became hypoactive and stopped feeding a few weeks after birth. Midbrain dopaminergic neurons, their projections, and most characteristics of their target neurons in the striatum appeared normal. Within a few minutes of being injected with L-dihdroxyphenylalanine (L-DOPA), the product of TH, the DA-/- mice became more active and consumed more food than control mice. With continued administration of L-DOPA, nearly normal growth was achieved. These studies indicate that DA is essential for movement and feeding, but is not required for the development of neural circuits that control these behaviors.

Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.