Hippocampal plasticity after a vagus nerve injury in the rat.
Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus, leading to alteration of neurogenesis.
Department of Clinical and Biological Sciences, University of Turin, Turin 10043, Italy ; Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation (NICO), University of Turin, Turin 10043, Italy.
Giulia
G
Ronchi
Programs in Neuroscience and Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Vitaly
V
Ryu
Department of Anatomy, Midwestern University, Downers Grove, IL60515, USA.
Michele
M
Fornaro
Programs in Neuroscience and Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Krzysztof
K
Czaja
capsaicin; hippocampus; microglia; rat; vagal afferents; vagotomy; vagus injury