A neurovascular survival axis for adult sympathetic neurons.

Adult intracranial arteries supply Ntn4, a neurovascular factor critical for maintaining specific sympathetic neurons, with Ntn4 decline linked to neuronal loss in mice.

• Why it matters: Understanding how adult neurons survive long-term is essential for addressing neurodegenerative conditions and age-related neuronal decline, yet the mechanisms are poorly understood.
• What they did: The study used genetic deletion and recombinant Ntn4 delivery in mice to demonstrate that arterial Ntn4 sustains intracranial-projecting sympathetic neurons via a local neurovascular axis, involving DCC receptor signaling.
• The result: Loss of arterial Ntn4 causes selective neuronal attrition through a caspase-independent death pathway, which can be prevented by Ntn4 overexpression, highlighting a potential target for preserving neuronal health with age.