Neuroscience 2000 Abstract
| Presentation Number: | 32.13 |
|---|---|
| Abstract Title: | Brain adenylyl cyclase and phospholipase C signaling pathways in Alzheimer's disease and Down syndrome. |
| Authors: |
Lumbreras, M. A.*1
; Baamonde, C.1
; Lubec, G.3
; Cairns, N.4
; Crespo, D.2
; Martínez-Cué, C.1
; Dierssen, M.5
; Sallés, J.6
; Flórez, J.1
1Lab. Develop. Neurobiol., Dep. Physiol. Pharmacol, Santander, Spain 2Dep. Cell. Biol., Univ. Cantabria, Santander, Spain 3Dep. Pediatrics, Univ. Vienna, Vienna, Austria 4Inst. Psychiat., King's College, London, England, United Kingdom 5Cent. Med. Molec. Genetics, Barcelona, Spain 6Dep. Pharmacol, Univ. País Vasco, Vitoria, Spain |
| Primary Theme and Topics |
A. Development and Regeneration - 24. Developmental disorders |
| Secondary Theme and Topics | J. Disorders of the Nervous System and Aging<br />- 129. Degenerative disease: Alzheimer's-neuropharmacology and neurotransmitters |
| Session: |
32. Developmental disorders III Poster |
| Presentation Time: | Sunday, November 5, 2000 8:00 AM-9:00 AM |
| Location: | Hall G-J |
| Keywords: | Cyclic AMP, Inositol Phosphate, Down Syndrome, Alzheimer Disease |
Several genes located in the obligate region of chromosome 21 for Down syndrome (DS), including the APP gene, have also been implicated in the etiology of Alzheimer's disease (AD). We reported abnormal patterns of adenylyl cyclase (AC) functioning in several brain areas of the DS mouse model Ts65Dn and of two children with DS (Lumbreras et al., SFN 1999), and of phospholipase C (PLC) in Ts65Dn mice (Sallés et al., SFN 1998). We examine AC and PLC activities in cerebral cortex of 4 adults with DS, 4 with AD, and 4 controls (C). AC signaling was assessed by determining cAMP formation in isolated membranes under basal conditions and after stimulation with GTP γS (10 μM), norepinephrine (NE, 100 μM), SKF38393 (10 μM) and forskolin (FK, 100 μM). PLC was assessed by analyzing the breakdown of [3H] PIP2 into [3H]inositol phosphates under basal conditions and after stimulation with GTPγS (3 μM), 5-methyltryptamine (300 μM), carbachol (1 mM) and calcium (10 μM). Basal production of cAMP was significantly reduced in DS brains. Statistically significant lower production of cAMP was obtained in DS and AD compared to C brains after stimulation with GTPγS, NE, SKF and FK (p<.001). In all conditions, values were also significantly lower in DS than in AD (p<.001). No differences between C, DS and AD brains were observed in PLC activity under basal and GTPγS- and Ca-stimulated conditions. However, the response of DS brains to serotonergic and cholinergic stimulation was significantly depressed, and that of AD brains was only to cholinergic stimulation. It is concluded that AC and PLC signaling pathways are severely disturbed in the brain of adult DS, to a greater extent and in a differential manner than in AD brain.
Supported by Grants SAF99-0092-C02-02, FIS 00/0795, and M. de Valdecilla and M. Bot&iacute;n Foundations
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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