Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury

• DOI: 10.3389/fncel.2023.1163436
• Publication Date: 2023-06-21T09:52:20Z
• Authors: Carlos A. Toro; Kaitlin Johnson; Jens Hansen; Mustafa M. Siddiq; Walter Vásquez; Wei Zhao; Zachary A. Graham; Juan C. Sáez; Ravi Iyengar; Christopher P. Ca...
• Keywords: 0301 basic medicine; 570; glial response; functional recovery; 610; contusion SCI; Neurosciences. Biological psychiatry. Neuropsychiatry; boldine; hemichannel blockade; spared white matter; 3. Good health; connexins; 03 medical and health sciences; 03 Salud y bienestar; 03 Good Health and Well-being; RC321-571; Neuroscience

Membrane channels such as those formed by connexins (Cx) and P2X 7 receptors (P2X R) are permeable to calcium ions other small molecules adenosine triphosphate (ATP) glutamate. Release of ATP glutamate through these is a key mechanism driving tissue response traumas spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx Panx1 hemichannels (HCs). To test if boldine could improve function after SCI, or vehicle was administered treat mice with moderate severity contusion-induced SCI. Boldine led greater spared white matter increased locomotor determined Basso Mouse Scale horizontal ladder rung walk tests. treatment reduced immunostaining for markers activated microglia (Iba1) astrocytic (GFAP) while increasing that axon growth neuroplasticity (GAP-43). Cell culture studies demonstrated blocked glial HC, specifically Cx26 Cx30, in cultured astrocytes entry R. RT-qPCR showed expression chemokine Ccl2, cytokine IL-6 microglial gene CD68, neurotransmission genes Snap25 Grin2b, Gap-43. Bulk RNA sequencing revealed modulated large number involved just caudal lesion epicenter at 14 days Numbers regulated much lower 28 injury. These results indicate ameliorates spares increase function.