Kolasa K, Harrell LE (2003) Combined lesions of central cholinergic and noradrenergic denervation in the rat using 192 IgG-saporin and DSP-4 as an animal model of Alzheimer’s disease. Neuroscience 2003 Abstracts 842.6. Society for Neuroscience, New Orleans, LA.
Summary: To better model the consequences of persistent cholinergic hypofunction observed in Alzheimer’s disease, medial septum (MS) lesions were made by using specific cholinotoxin 192-IgG saporin. In this study the effect of simultaneous hippocampal cholinergic denervation, induced by intraseptal injection of 192-IgG saporin, and central noradrenergic denervation, induced by systemic injection of DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine) was examined in the rat dorsal hippocampus. DSP-4, an adrenergic neurotoxin selective for locus coeruleus innervated brain regions, induced a decrease in norepinephrine (NE) concentration in hippocampus. MS lesions resulted not only in selective cholinergic denervation of hippocampus (CD; superior cervical ganglion removed to prevent ingrowth of peripheral NE fibers), but also ingrowth of NE fibers into the hippocampus (HI; superior cervical ganglion left intact). MS lesions also resulted in a significant loss of choline-acetyltransferase activity in HI and CD groups, and an increase in NE in the HI group. In the HI group, but not in CD or control groups, visualization of hippocampus revealed a dense NE innervation with fine NE fibers with varicosities. Combination of MS lesion and DSP-4 treatment resulted in a reduction of NE concentration in HI group, with concomitant decrease in visualization of NE fibers. Those that remained were thick with sparse varicosities, possibly derived from peripheral sympathetic ingrowth. Elevated NE concentration and NE fiber number following specific cholinergic lesions might reflect compensatory sprouting of both central and peripheral adrenergic fibers into the hippocampus. Thus, noradrenergic sprouting in response to cholinergic denervation of hippocampus might be a valuable model for studying mechanisms as well as the consequences of neuronal plasticity in the mature CNS.
Related Products: 192-IgG-SAP (Cat. #IT-01)