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Titolo:
beta-amyloid((1-42))-induced cholinergic lesions in rat nucleus basalis bidirectionally modulate serotonergic innervation of the basal forebrain and cerebral cortex
Autore:
Harkany, T; OMahony, S; Keijser, J; Kelly, JP; Konya, C; Borostyankoi, ZA; Gorcs, TJ; Zarandi, M; Penke, B; Leonard, BE; Luiten, PGM;
Indirizzi:
Univ Groningen, Dept Anim Physiol, NL-9750 AA Haren, Netherlands Univ Groningen Haren Netherlands NL-9750 AA L-9750 AA Haren, Netherlands Beres Co Ltd, Trace Element Res Ctr, Budapest, Hungary Beres Co Ltd Budapest Hungary Trace Element Res Ctr, Budapest, Hungary Natl Univ Ireland Univ Coll Galway, Dept Pharmacol, Galway, Ireland Natl Univ Ireland Univ Coll Galway Galway Ireland acol, Galway, Ireland Univ Dusseldorf, C&O Vogt Inst Brain Res, D-4000 Dusseldorf, Germany Univ Dusseldorf Dusseldorf Germany D-4000 es, D-4000 Dusseldorf, Germany Hungarian Acad Sci, United Res Org, Neurobiol Res Grp, Budapest, Hungary Hungarian Acad Sci Budapest Hungary eurobiol Res Grp, Budapest, Hungary Semmelweis Univ Med, H-1085 Budapest, Hungary Semmelweis Univ Med Budapest Hungary H-1085 ed, H-1085 Budapest, Hungary Univ Szeged, Dept Med Chem, H-6720 Szeged, Hungary Univ Szeged Szeged Hungary H-6720 Dept Med Chem, H-6720 Szeged, Hungary
Titolo Testata:
NEUROBIOLOGY OF DISEASE
fascicolo: 4, volume: 8, anno: 2001,
pagine: 667 - 678
SICI:
0969-9961(200108)8:4<667:BCLIRN>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; CA2+ ANTAGONIST NIMODIPINE; ALZHEIMERS-DISEASE; RAPHE DORSALIS; ANXIETY DISORDERS; CALCIUM CHANNELS; CORTICAL-NEURONS; NMDA RECEPTOR; BETA-PROTEIN; HIPPOCAMPUS;
Keywords:
beta-amyloid; anxiety; magnocellular nucleus basalis; serotonin; sprouting;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Harkany, T Univ Groningen, Dept Anim Physiol, Kerklaan 30, NL-9750 AA Haren, Netherlands Univ Groningen Kerklaan 30 Haren Netherlands NL-9750 AA rlands
Citazione:
T. Harkany et al., "beta-amyloid((1-42))-induced cholinergic lesions in rat nucleus basalis bidirectionally modulate serotonergic innervation of the basal forebrain and cerebral cortex", NEUROBIOL D, 8(4), 2001, pp. 667-678

Abstract

Ample experimental evidence suggests that beta -amyloid (A beta), when injected into the rat magnocellular nucleus basalis (MBN), impels excitotoxic injury of cholinergic projection neurons. Whereas learning and memory dysfunction is a hallmark of A beta -induced cholinergic deficits, anxiety, or hypoactivity under novel conditions cannot be attributed to the loss of cholinergic MBN neurons. As mood-related behavioral parameters are primarily influenced by the central serotonergic system, in the present study we investigated whether A beta ((1-42)) toxicity in the rat MBN leads to an altered serotonergic innervation pattern in the rat basal forebrain and cerebral cortex 7 days postsurgery. A beta infusion into the MBN elicited significant anxiety in the elevated plus maze. A beta toxicity on cholinergic MBN neurons, expressed as the loss of acetylcholinesterase-positive cortical projections, was accompanied by sprouting of serotonergic projection fibers in theMBN. In contrast, the loss of serotonin-positive fiber projections, decreased concentrations of both serotonin and 5-hydroxyindoleacetic acid, and decline of cortical 5-HT1A receptor binding sites indicated reduced serotonergic activity in the somatosensory cortex. In conclusion, the A beta -induced primary cholinergic deficit in the MBN and subsequent cortical cholinergic denervation bidirectionally modulate serotonergic parameters in the rat basal forebrain and cerebral cortex. We assume that enhanced serotonin immunoreactivity in the damaged MBN indicates intrinsic processes facilitating neuronal recovery and cellular repair mechanisms, while diminished cortical serotonergic activity correlates with the loss of the subcortical cholinergic input, thereby maintaining the balance of neurotransmitter concentrations in the cerebral cortex. (C) 2001 Academic Press.

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Documento generato il 25/01/20 alle ore 06:27:31