Degeneration of the basalocortical pathway from the cortex induces a functional increase in galaninergic markers in the nucleus basalis magnocellularis of the rat.
The present work aimed 1) to evaluate whether an increase in galanin or galanin receptors could be induced in the nucleus basalis magnocellularis (nbm) by degeneration of the basalocortical neurons from the cortex and 2) to analyze the consequences of such an increase on cortical activity. First, a mild ischemic insult to the frontoparietal cortex was performed to induce the degeneration of the basalocortical system; galanin immunoreactivity, galanin binding sites, and cholinergic muscarinic receptors were quantified through immunocytochemistry and autoradiography. Second, galanin infusions in the nbm were undertaken to mimic a local increase of the galaninergic innervation; cortical acetylcholine release, cerebral glucose use, and cerebral blood flow were then measured as indices of cortical activity. As a result of the cortical ischemic lesion, the postsynaptic M1 and presynaptic M2 muscarinic receptors were found to be reduced in the altered cortex. In contrast, galaninergic binding capacity and fiber density were found to be increased in the ipsilateral nbm in parallel with a local decrease in the cholinergic markers such as the muscarinic M1 receptor density. Galanin infusion into the nbm inhibited the cortical acetylcholine release and cerebral blood flow increases elicited by the activation of the cholinergic basalocortical system but failed to affect acetylcholine release, cerebral blood flow, and cerebral glucose use when injected alone in the nbm. These results demonstrate that degeneration of the basalocortical system from the cortex induces an increase in galaninergic markers in the nbm, a result that might suggest that the galaninergic overexpression described in the basal forebrain of patients with Alzheimer's disease can result from a degeneration of the cholinergic basalocortical system from the cortex. Because galanin was found to reduce the activity of the basalocortical cholinergic system only when this one is activated, galanin might exert its role rather during activation deficits than under resting conditions such as the resting cortical hypometabolism, which is characteristic of Alzheimer's disease.
Barbelivien
Alexandra
A
Université de Caen, UMR 6185 CNRS, Centre Cyceron, France.
Vaussy
Claire
C
Marchalant
Yannick
Y
Maubert
Eric
E
Bertrand
Nathalie
N
Beley
Alain
A
Roussel
Simon
S
Mackenzie
Eric T
ET
Dauphin
François
F
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D019004:Galanin / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D044088:Receptors, Galanin / Q000378:metabolism
D015415:Biomarkers; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D044088:Receptors, Galanin; D019004:Galanin; D000109:Acetylcholine