Hippocampal sympathetic ingrowth and cholinergic denervation alter hippocampal muscarinic cholinergic receptors

Abstract

Cholinergic denervation of the hippocampus by medial septal (MS) lesions results in the ingrowth of peripheral sympathetic fibers, originating from the superior cervical ganglia, into the hippocampus. To determine the effect of hippocampal sympathetic ingrowth (HSI) [3H]-QNB (L-quinuclidinyl [benzilic-4,4(n)] binding was assessed in the dorsal and ventral hippocampus four weeks after MS lesions. In dorsal hippocampus, HSI was found to significantly increase the number (Bmax) of [3H]-QNB binding sites and to normalize the decrease in affinity found in animals with MS lesions plus ganglionectomy (i.e., no ingrowth). In ventral hippocampus, HSI was found to normalize the increased number of binding sites and decreased affinity found in animals with MS lesions without ingrowth. No effect on either Kd or Bmax was found in animals that had undergone ganglionectomy with sham MS lesions. These results suggest that HSI can induce changes in hippocampal muscarinic cholinergic receptors.

The Fimbria-Fornix/Cingular Bundle Pathways: A Review of Neurochemical and Behavioural Approaches Using Lesions and Transplantation Techniques

“…It is also noteworthy that some of the aforementioned lesion-induced changes in receptor sensitivity, especially as regards the muscarinic receptors, can be partially altered (generally attenuated) by the ingrowth of sympathetic noradrenergic fibres originating in the superior cervical ganglia (e.g. Harrell et al, 1994Harrell et al, , 1995Kolasa et al, 1995). Gage et al (1983b) performed bilateral fimbriafornix aspirations which, three weeks later, had decreased the NA concentration by 90%, 55~0 and 20Y0 in the dorsal, "middle" (a part intermediate between the dorsal and ventral thirds of the hippocampus) and ventral hippocampal regions, respectively.…”

Modulation of 5-hydroxytryptamine release in hippocampal slices of rats: Effects of fimbria-fornix lesions on 5-HT1b-autoreceptor and α2-heteroreceptor function

“…Although this sprouting reaction of sympathetic neurons has been well-characterized neuroanatomically [14], there are only a few-sometimes contradictory-behavioral studies (e.g. [4,13,17,33,36]), some reports about electrophysiological approaches [6,44] and several neuropharmacological investigations [5,31,32,34,35,45,54] of this phenomenon. Interestingly, it has been shown that sympathetic sprouting may also occur in the brains of patients with Alzheimer's disease [7].…”

Phänotypische und molekulare Analyse einer Maus mit Insertionsmutation und axonaler Reorganisation im Hippocampus

“…In früheren Arbeiten dieser Arbeitsgruppe konnte nach isolierter cholinerger Denervierung (CD) in hippocampalen Extrakten bereits eine Verminderung der Carbachol-stimulierten PIP 2 -Hydrolyse nachgewiesen werden (Connor und Harrell 1989;Harrell et al 1992). Die cholinerge Denervierung geht mit kompensatorischen Veränderungen in der hippocampalen Verteilung der muscarinischen Acetycholin-Rezeptoren (mAChR) einher (Harrell et al 1994;Kolasa et al 1995). Die Anzahl der M1-Acetylcholin-Rezeptoren ist im cholininerg denervierten Hippocampus von Ratten signifikant erhöht, während die Anzahl der M2-Acetylcholin-Rezeptoren signifikant vermindert ist.…”