BRIEF REPORT |
Correspondence to: P. Pompei, Dept. of Pharmacological Sciences & Experimental Medicine, University of Camerino, Via Scalzino 3, Camerino MC-62032, Italy. E-mail: pompei@cambio.unicam.it
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Introduction |
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ALZHEIMER'S DISEASE is a neurodegenerative disorder of the CNS characterized by deposition of neuritic plaques and neurofibrillary tangles with consequent neuron death. Clinically it is characterized by a progressive loss of memory and impairment of learning capacity (
Substance P (SP) is a neurotransmitter related to memory functions and learning properties, highly expressed in several brain areas from forebrain to hindbrain (
On the basis of these findings, the aim of this study was to verify the presence and the distribution of preprotachykinin-A (PPT-A) mRNA in discrete brain areas in an animal model of Alzheimer's disease.
Twenty male Albino Wistar rats weighing 340 g were implanted SC with miniosmotic infusion pumps (Alzet type) that deliver the mixed neurotoxins to the hippocampus via a catheterized cannula (
Experimental animals included four groups (five animals each group). The first group (vehicle) was infused with a saline solution. The second group was infused with a solution of 0.075 µg/µl of ß-amyloid (fragment 140) and 0.01875 µg/µl of ibotenic acid (A dose). The third group was infused with a solution of 0.15 µg/µl of ß-amyloid (fragment 140) and 0.0375 µg/µl of ibotenic acid (B dose). The fourth group was infused with a solution of 0.224 µg/µl of ß-amyloid (fragment 140) and 0.0562 µg/µl of ibotenic acid (C dose). Finally, on Day 10, rats were sacrificed by decapitation and the brains were removed and then stored for in situ hybridization. Semiquantitative ISH histochemistry examined PPT-A mRNA levels in the bed nucleus of the stria terminalis (BNST) in the medial preoptic area (MPA).
The infusion of the two neurotoxins ß-amyloid (fragment 140) and ibotenic acid induced a 24.29% statistically significant reduction in basal hybridizable PPT-A mRNA in the BNST brain area after administration with dose A, as well as a 19.26% and a 16.85% statistically significant decrease after administration with dose B and dose C compared to CON rats, respectively (Fig 1).
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The same figure shows a 30.7% statistically significant lower level of PPT-A mRNA in MPA after dose A, whereas PPT-A mRNA levels were shown to be significantly lower by 22.00% and by 19.01% after dose B and dose C in MPA in ß-amyloid (fragment 140) and ibotenic acid-treated animals compared to CON rats.
The decrease in PPT-A mRNA levels shown in the present study might contribute to the loss of memory and impairment of learning capacity seen in AD, thus suggesting a role of the tachykinergic system as a putative co-factor in the etiopathogenesis of AD.
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Acknowledgments |
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Supported by the Fondazione Cassa di Rispormio, Provincia di Maceratao.
Received for publication November 29, 2000; accepted February 16, 2001.
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