Selective nicotinic receptor consequences in APP(SWE) transgenic mice.
ABSTRACT The nicotinic (nAChRs) and muscarinic (mAChRs) acetylcholine receptors and acetylcholinesterase (AChE) activity were studied in the brains of APP(SWE) transgenic mice (Tg+) and age-matched nontransgenic controls (Tg-) that were between 4 and 19 months of age. A significant increase in the binding of 125I-labeled alpha-bungarotoxin (alpha7 nAChRs) was observed in most brain regions analyzed in 4-month-old Tg+ mice, preceding learning and memory impairments and amyloid-beta (Abeta) pathology. The enhanced alpha7 receptor binding was still detectable at 17-19 months of age. Increase in [3H]cytisine binding (alpha4beta2 nAChRs) was measured at 17-19 months of age in Tg+ mice, at the same age when the animals showed heavy Abeta pathology. No significant changes in [3H]pirenzepine (M1 mAChRs) or [3H]AFDX 384 (M2 mAChRs) binding sites were found at any age studied. The upregulation of the nAChRs probably reflects compensatory mechanisms in response to Abeta burden in the brains of Tg+ mice.
- Annual Review of Physiology 02/1995; 57:521-46. · 19.55 Impact Factor
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ABSTRACT: Transgenic mouse strains were generated that overexpress human APP or clinical mutants of APP. All transgenic mouse strains that over-express APP displayed essentially the same phenotype of disturbed behaviour, differential glutamatergic responses, deficits in maintenance of long-term potentiation and premature death, but formation of amyloid plaques was seen in the highest expressing APP/London transgenic mice only. Apart from cognitive deficits, the APP transgenic mice were characterized by aggressive behaviour, which was pharmacologically alleviated with 8-OH-DPAT and buspirone, two serotonergic agonists. The atypical neuroleptic drug risperidone was equally active in this regard. The data establish an important aspect of the transgenic mice as experimental models for behavioural aspects of Alzheimer's disease, in addition to other early and late symptoms.Neuroreport 12/1998; 9(16):3561-4. · 1.40 Impact Factor
- Journal of Neurochemistry - J NEUROCHEM. 01/2002; 70(5):2179-2187.