Grant: Operating Grant

Following spinal cord injury, loss of brainstem and cortical innervation of the spinal cord results in a complex and devastating loss of function, including loss of movement and sensation and even impaired blood flow. The spinal neurons, sensory afferents and blood vessels below the injury remain largely intact and viable, except that they have many receptors without activation from neurotransmitters, because of loss of descending axons from the brain. Previously, we have shown that some of these receptors can become constitutively active, whereas others do not. Here we explore the additional possibility that these other receptors may regain their activity in a different way: by the spinal cord synthesizing novel neurotransmitters to replace the lost innervation. We specifically propose that de novo synthesis of trace amines from readily available dietary amino acids (protein) can in part replace the lost monoamine innervation after injury, especially in locations rich in the enzyme AADC (aromatic amino acid decarboxylase) responsible for trace amine production, including in pericytes on spinal capillaries and dorsally located AADC-containing neurons that emerge after injury. We will examine pharmacological methods to manipulate trace amine action, opening up novel therapeutic methods for treating spinal cord injury, including reducing spasticity and muscle spasms, improving blood supply to the injured spinal cord, and promoting recovery of locomotion (walking).