QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 26, 2005, 25(4):823-829; doi:10.1523/JNEUROSCI.4335-04.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (45) Citing Articles via Google Scholar Google Scholar Articles by Basha, M. R. Articles by Zawia, N. H. Search for Related Content PubMed PubMed Citation Articles by Basha, M. R. Articles by Zawia, N. H.

 Previous Article  |  Next Article 

Neurobiology of Disease
The Fetal Basis of Amyloidogenesis: Exposure to Lead and Latent Overexpression of Amyloid Precursor Protein and -Amyloid in the Aging Brain

M. Riyaz Basha,¹ Wei Wei,¹ Saleh A. Bakheet,¹ Nathalie Benitez,¹ Hasan K. Siddiqi,¹ Yuan-Wen Ge,² Debomoy K. Lahiri,² and Nasser H. Zawia¹

¹Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island 02881, and ²Laboratory of Molecular Neurogenetics, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202

The fetal basis of adult disease (FeBAD) hypothesis states that many adult diseases have a fetal origin. According to FeBAD, injury or environmental influences occurring at critical periods of organ development could result in "programmatic" changes via alterations in gene expression or gene imprinting that may result in functional deficits that become apparent later in life. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by excessive deposits of aggregated -amyloid (A) peptides, which are snippets of the -amyloid precursor protein (APP). The predominately sporadic nature of AD suggests that the environment must play a role in neurodegeneration. To examine latent responses to an environmental agent, we exposed rodents to lead and monitored the lifetime expression of the APP gene. We observed that APP mRNA expression was transiently induced in neonates, but exhibited a delayed overexpression 20 months after exposure to Pb had ceased. This upregulation in APP mRNA expression was commensurate with a rise in activity of the transcription factor Sp1, one of the regulators of the APP gene. Furthermore, the increase in APP gene expression in old age was accompanied by an elevation in APP and its amyloidogenic A product. In contrast, APP expression, Sp1 activity, as well as APP and A protein levels were unresponsive to Pb exposure during old age. These data suggested that environmental influences occurring during brain development predetermined the expression and regulation of APP later in life, potentially altering the course of amyloidogenesis.

Key words: Alzheimer; -peptide; CNS; dementia; development; environment; latency; transcription

---

Received Oct 19, 2004; revised December 3, 2004; accepted December 4, 2004.

This article has been cited by other articles:

				N. Healey Lead toxicity, vulnerable subpopulations and emergency preparedness Radiat Prot Dosimetry, June 1, 2009; 134(3-4): 143 - 151. [Abstract] [Full Text] [PDF]

				J. Wu, Md. R. Basha, B. Brock, D. P. Cox, F. Cardozo-Pelaez, C. A. McPherson, J. Harry, D. C. Rice, B. Maloney, D. Chen, et al. Alzheimer's Disease (AD)-Like Pathology in Aged Monkeys after Infantile Exposure to Environmental Metal Lead (Pb): Evidence for a Developmental Origin and Environmental Link for AD J. Neurosci., January 2, 2008; 28(1): 3 - 9. [Abstract] [Full Text] [PDF]

				D. K. Lahiri, D. Chen, B. Maloney, H. W. Holloway, Q.-s. Yu, T. Utsuki, T. Giordano, K. Sambamurti, and N. H. Greig The Experimental Alzheimer's Disease Drug Posiphen [(+)-Phenserine] Lowers Amyloid-beta Peptide Levels in Cell Culture and Mice J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 386 - 396. [Abstract] [Full Text] [PDF]

				M. D. Anway, M. A. Memon, M. Uzumcu, and M. K. Skinner Transgenerational Effect of the Endocrine Disruptor Vinclozolin on Male Spermatogenesis J Androl, November 1, 2006; 27(6): 868 - 879. [Abstract] [Full Text] [PDF]

				M. D. Anway and M. K. Skinner Epigenetic Transgenerational Actions of Endocrine Disruptors Endocrinology, June 1, 2006; 147(6): s43 - s49. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help