engleski

Alteration of cholinergic transmission and memory functions in the non-transgenic model of sporadic Alzheimer's disease

Introduction Sporadic Alzheimer’s disease (sAD) is associated with cognitive deficits and reduced brain expression of cholinergic receptors, development of which is difficult to track in humans. Streptozotocin (STZ, a nitrosourea derivative)- intracerebroventricularly (icv) treated rat represents an experimental sAD model suitable for determining neurochemical and cognitive impairments but cholinergic deficits have been investigated up to 1 month post STZ-icv only. Methods Adult, male Wistar rats were injected icv with three STZ doses (0, 3-3 mg/kg) or vehicle only (controls) and sacrificed three months after the treatment. Cognitive functions were tested by Morris Water Maze Swimming (MWM) and Passive Avoidance (PA) Test before sacrifice. Protein expression of cholinergic muscarinic M1, and nicotinic α7 receptors was measured in the hippocampus (HPC) and parietotemporal cortex (PTC) by SDS-PAGE electrophoresis and immunoblotting. Data were analysed by Kruskal-Wallis and Mann- Whitney U test (p<0.05). Results In comparison to the control animals, learning and memory functions in the STZ-icv treated rats were found significantly decreased with 1 and 3 mg dose in both tests (-46, 67% and -66, 79% by PA ; -38, 86% and -36, 48% by MWM, respectively). One and 3 mg STZ dose significantly altered the expression of muscarinic M1 receptors, manifested as increment in PTC (+82, 89% and +67, 83%) and decrement in HPC (-18, 06% and 15, 01%), respectively, while nicotinic α7 receptor expression remained unaltered. Conclusion Results show that STZ-icv treatment induces dose- dependent cognitive deficits and cholinergic receptor type-dependent alterations which seem to be also brain region- dependent, suggesting a possible environmental toxin-induced sAD etiopathogenesis. Acknowledgement Supported by UKF and MZOS (108- 1080003-0020).

learning and memory; streptozotocin; cholinergic neurotransmission

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