Impaired Neural Transmission and Synaptic Plasticity in Superior Cervical Ganglia from β-Amyloid Rat Model of Alzheimers Disease

Author(s): K. H. Alzoubi , I. A. Alhaider , T. T. Tran , A. Mosely , K. A. Alkadhi .

Journal Name: Current Alzheimer Research

Volume 8 , Issue 4 , 2011

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Abstract:

Basal synaptic transmission and activity-dependent synaptic plasticity were evaluated in superior cervical sympathetic ganglia (SCG) of amyloid-β rat model of Alzheimers disease (Aβ rat) using electrophysiological and molecular techniques. Rats were administered Aβ peptides (a mixture of 1:1 Aβ1-40 and Aβ1-42) by chronic intracerebroventricular infusion via 14-day mini-osmotic pumps (300 pmol/day). Control rats received Aβ40-1 (inactive reverse peptide: 300 pmol/day). Ganglionic compound action potentials were recorded before (basal) and after repetitive stimulation. In isolated SCG, ganglionic long-term potentiation (gLTP) was generated by a brief train of stimuli (20Hz for 20s) and ganglionic long-term depression (gLTD) was produced with trains of paired pulses. The input/output (I/O) curves of ganglia from Aβ rats showed a marked downward shift along all stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission. In addition, repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals, but, the same protocols failed to induce gLTP or gLTD in ganglia from Aβ rats indicating impairment of activity-dependent synaptic plasticity in these animals. Western blotting of SCG homogenate from Aβ rats revealed reduction in the ratio of phosphorylated-/total-CaMKII and in calcineurin protein levels. Although other mechanisms could be involved, these changes in signaling molecules could represent an important molecular mechanism linked to the failure to express synaptic plasticity in Aβ rat ganglia. Results of the current study could explain some of the peripheral nervous system manifestations of Alzheimers disease.

Keywords: Alzheimer's disease, gLTP/kwd, >, gLTD, PTP, I/O curve, immunoblotting, CaMKII, calcineurin, sympathetic ganglia, Calcium influx, Western blotting

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2011
Page: [377 - 384]
Pages: 8
DOI: 10.2174/156720511795745311
Price: $58

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