Journal of Histochemistry and Cytochemistry, Vol. 49, 1469-1470, November 2001, Copyright © 2001, The Histochemical Society, Inc.


BRIEF REPORT

Regulation of Preprotachykinin-A Gene Expression in an Animal Model of Alzheimer's Disease

P. Pompeia, R. Severinib, D. Pediconia, M. Angelettib, A. Eleuterib, P. Fattorettic, C. Bertoni–Freddaric, and E. Fiorettib
a Department of Pharmacological Sciences and Experimental Medicine, INRCA, Ancona, Italy
b Specialty School of Clinical Biochemistry, INRCA, Ancona, Italy
c University of Camerino, Camerino, Italy, and Center for Surgical Research, Neurobiology of Aging Section, INRCA, Ancona, Italy

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


  Introduction
Top
Introduction
Literature Cited

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 (Selkoe 1997 ; Seabrook et al. 1999 ).

Substance P (SP) is a neurotransmitter related to memory functions and learning properties, highly expressed in several brain areas from forebrain to hindbrain (Rattan and Tejwani 1992 ; Alvarez et al. 1997 ). For example, the nucleus basalis of Meynert (NBM) is highly sensitive to memory enhancement effects of SP. SP also interacts with the cholinergic ascending system of the NBM that is implicated in memory functions. Patients with Alzheimer's disease show a marked loss of cholinergic neurons from the NBM to the cortex and diminished brain SP immunoreactivity (Cleary et al. 1995 ; Nag et al. 1999 ).

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 (Morimoto et al. 1998 ).

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 1–40) 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 1–40) 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 1–40) 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 1–40) 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).



View larger version (20K):
[in this window]
[in a new window]
 
Figure 1. ß-Amyloid (fragment 1–40) and ibotenic acid dose effects on PPT-A mRNA in BNST.

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 1–40) 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.


  Acknowledgments

Supported by the Fondazione Cassa di Rispormio, Provincia di Maceratao.

Received for publication November 29, 2000; accepted February 16, 2001.


  Literature Cited
Top
Introduction
Literature Cited

Alvarez XA, Miguel–Hidalgo JJ, Fernandez–Novoa L, Cacabelos R (1997) Intrahippocampal injections of the ß-amyloid 1-28 fragment induces behavioral deficits in rats. Methods Find Exp Clin Pharmacol 19:471-479[Medline]

Cleary J, Hittner JM, Semotuk M, Manty P, O'Hare E (1995) Beta-amyloid (1-40) effects on behavior and memory. Brain Res 682:69-74[Medline]

Morimoto K, Yoshimi K, Tonohiro T, Yamada N, Oda T, Kaneko I (1998) Co-injection of ß-amyloid with ibotenic acid induces synergistic loss of rat hippocampal neurons. Neuroscience 84:479-487[Medline]

Nag S, Yee BK, Tang F (1999) Reduction in somatostatin and substance P levels and choline acetyltransferase activity in the cortex and hippocampus of the rat after chronic intracerebroventricular infusion of ß-amyloid (1-40). Brain Res Bull 50:251-262[Medline]

Rattan AK, Tejwani GA (1992) The neurotoxic actions of ibotenic acid on cholinergic and opioid peptidergic systems in the central nervous system of the rat. Brain Res 7:298-305

Seabrook GR, Smith DW, Bowery BJ, Easter A, Reynolds T, Fitzjohn SM, Morton RA, Zheng H, Dawson GR, Sirianathsinghji DJS, Davies CH, Collingridge GL, Hill RG (1999) Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Neuropharmacology 38:349-359[Medline]

Selkoe DJ (1997) Alzheimer's disease: genotypes, phenotype, and treatments. Science 275:630-631[Free Full Text]





This Article
Abstract
Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Download to citation manager
Google Scholar
Articles by Pompei, P.
Articles by Fioretti, E.
Articles citing this Article
PubMed
PubMed Citation
Articles by Pompei, P.
Articles by Fioretti, E.


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]