Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and down's syndrome

Yates, Celia M.; Simpson, J. A.; Gordon, Alexander; Maloney, A. F. J.; Allison, Y.; Ritchie, Isobel M.; Urquhart, A. L.

doi:10.1016/0006-8993(83)91179-4

Cited by 249 publications

(106 citation statements)

References 33 publications

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“…Studies on DS patients suggest that BFCNs degenerate with increased age (3,4,22). This study significantly extends our previous work in demonstrating marked age-related abnormalities of BFCNs in Ts65Dn mice (6).…”

Section: Discussionsupporting

confidence: 83%

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Cooper

Salehi

Delcroix

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

315

312

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Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited reductions in BFCN size and number and regressive changes in the hippocampal terminal fields of these neurons with respect to diploid controls. The changes were associated with significantly impaired retrograde transport of nerve growth factor (NGF) from the hippocampus to the basal forebrain. Intracerebroventricular NGF infusion reversed well established abnormalities in BFCN size and number and restored the deficit in cholinergic innervation. The findings are evidence that even BFCNs chronically deprived of endogenous NGF respond to an intervention that compensates for defective retrograde transport. We suggest that age-related cholinergic neurodegeneration may be a treatable disorder of failed retrograde NGF signaling.

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Section: Discussionsupporting

confidence: 83%

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Cooper

Salehi

Delcroix

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

315

312

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“…Prior findings indicate that some markers of ACh function in Ts65Dn mice are intact at young ages but emerge in adulthood, generally evident after 6 months of age (Granholm, Sanders and Crnic, 2000). The development of cholinergic dysfunctions in Ts65Dn mice parallels a similar situation in humans with Down syndrome, in whom the basal forebrain cholinergic system appears normal at birth but degenerates in early adulthood (Casanova et al, 1985;Head et al, 2001;Yates et al, 1983). The cholinergic neurons that project to the hippocampus and provide the source of the ACh release measured in the present experiment are located in the medial septum.…”

Section: Acetylcholine Releasementioning

confidence: 91%

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.

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“…One hallmark neuropathological abnormality in Ts65Dn is an age-related loss of immunoreactive BFCNs (9), which mimics the age-related dysfunction in BFCNs seen in DS and AD (28). BFCNs play an important role in attention, memory, and learning, and their degeneration may contribute to the dementia of DS and AD (11).…”

Section: Discussionmentioning

confidence: 99%

Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities

Sago

Carlson

Smith

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

355

317

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A mouse model for Down syndrome, Ts1Cje, has been developed. This model has made possible a step in the genetic dissection of the learning, behavioral, and neurological abnormalities associated with segmental trisomy for the region of mouse chromosome 16 homologous with the socalled ''Down syndrome region'' of human chromosome segment 21q22. Tests of learning in the Morris water maze and assessment of spontaneous locomotor activity reveal distinct learning and behavioral abnormalities, some of which are indicative of hippocampal dysfunction. The triplicated region in Ts1Cje, from Sod1 to Mx1, is smaller than that in Ts65Dn, another segmental trisomy 16 mouse, and the learning deficits in Ts1Cje are less severe than those in Ts65Dn. In addition, degeneration of basal forebrain cholinergic neurons, which was observed in Ts65Dn, was absent in Ts1Cje.

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Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and down's syndrome

Cited by 249 publications

References 33 publications

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities

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