Hunter CL, Quintero EM, Gilstrap L, Bhat NR, Granholm AE (2003) Neuroinflammatory response to mu p75-saporin immunotoxin-induced degeneration of basal forebrain cholinergic neurons. Neuroscience 2003 Abstracts 527.15. Society for Neuroscience, New Orleans, LA.
Summary: Basal forebrain cholinergic neurons, which provide the major cholinergic innervation to the cortical regions and play a key role in the processing of information involved in cognitive processes, degenerate during both normal aging and Alzheimer’s disease. Neuroinflammation, specifically the activation of microglia, is known to affect the progression of neuronal degeneration. Activated microglia produce inflammatory mediators that have neuropathic as well as neuroprotective actions, and it has been suggested that inflammatory mediators produced by activated microglia may play a role in the decline of specific neuronal sub-types in neurodegenerative diseases. The immunotoxin mu p75-SAP has been shown to selectively destroy cholinergic neurons in the basal forebrain of mice, resulting in reduced choline acetyl-transferase activity and cognitive impairments. To characterize the inflammatory response to mu p75-SAP lesions, 3 month-old mice received icv injections of mu p75-SAP (3.6 mg) followed by treatment with an anti-inflammatory agent, minocycline (45 mg/kg i.p.), or saline. Seven days after lesioning, immunohistochemistry was used to analyze markers for cholinergic and non-cholinergic neurons and inflammation. Cholinergic lesioning resulted in a dramatic increase in CD45, a microglial marker, but no change in GFAP, an astroglial marker, in the basal forebrain region. Lesioned animals had elevated levels of phosphorylated p38, a MAP kinase protein involved in inflammatory pathways. Minocycline treatment reduced this inflammatory response. Furthermore, preliminary results suggest that animals treated with minocycline after mu p75-SAP lesioning are partially protected from cholinergic degeneration.
Related Products: mu p75-SAP (Cat. #IT-16)