Reversal of Diabetes Insipidus in Brattleboro Rats: Intrahypothalamic Injection of Vasopressin mRNA

Abstract

Messenger RNAs occur within the axons of magnocellular hypothalamic neurons known to secrete oxytocin and vasopressin. In Brattleboro rats, which have a genetic mutation that renders them incapable of vasopressin expression and secretion and thus causes diabetes insipidus, injection into the hypothalamus of purified mRNAs from normal rat hypothalami or of synthetic copies of the vasopressin mRNA leads to selective uptake, retrograde transport, and expression of vasopressin exclusively in the magnocellular neurons. Temporary reversal of their diabetes insipidus (for up to 5 days) can be observed within hours of the injection. Intra-axonal mRNAs may represent an additional category of chemical signals for neurons.