Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats: Implications for β-amyloid

Ming D. Li, Justin K. Kane, Shannon G. Matta, William S. Blaner, Burt Sharp

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Epidemiological studies indicated that cigarette smoking protects against the development of several neurodegenerative disorders, including Alzheimer's disease (AD). However, the molecular mechanism(s) underlying this is poorly understood. To gain insight into these protective effects, we used differential display PCR (DD-PCR) to amplify RNA from various brain regions of rats self-administering (SA) nicotine compared with yoked-saline controls. We found that the transthyretin (TTR) gene, whose product has been shown to bind to amyloid β (Aβ) protein and prevent Aβ aggregation, was more abundantly expressed (~1.5- to 2.0-fold) in the brainstem and hippocampus (areas containing choroid plexus) of nicotine SA rats. Subsequently, quantitative reverse transcription-PCR analysis confirmed these DD-PCR findings and demonstrated that nicotine increased TTR mRNA levels in these regions in a time- and dose-dependent manner. Significantly higher TTR protein concentrations were also detected in the ventricular CSF of nicotine- treated rats. In contrast, no differences either in plasma TTR or in CSF and plasma retinol-binding protein were detected. Immunohistochemical analysis showed that immunoreactive TTR was 41.5% lower in the choroid plexus of nicotine-treated rats compared with the saline controls. On the basis of these data, we speculate that the protective effects of nicotine on the development of AD may be attributable, in part, to the increased biosynthesis and secretion of TTR from the choroid plexus. These findings also point toward new approaches that may take advantage of the potentially novel therapeutic effects of nicotinic agonists in patients with AD.

Original languageEnglish (US)
Pages (from-to)1318-1323
Number of pages6
JournalJournal of Neuroscience
Volume20
Issue number4
StatePublished - Feb 15 2000

Fingerprint

Choroid Plexus
Prealbumin
Nicotine
Amyloid
Alzheimer Disease
Polymerase Chain Reaction
Plasma Retinol-Binding Proteins
Nicotinic Agonists
Serum Amyloid A Protein
Therapeutic Uses
Neurodegenerative Diseases
Brain Stem
Reverse Transcription
Epidemiologic Studies
Hippocampus
Smoking
RNA
Messenger RNA
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats : Implications for β-amyloid. / Li, Ming D.; Kane, Justin K.; Matta, Shannon G.; Blaner, William S.; Sharp, Burt.

In: Journal of Neuroscience, Vol. 20, No. 4, 15.02.2000, p. 1318-1323.

Research output: Contribution to journalArticle

Li, Ming D. ; Kane, Justin K. ; Matta, Shannon G. ; Blaner, William S. ; Sharp, Burt. / Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats : Implications for β-amyloid. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 4. pp. 1318-1323.
@article{e1b2cc3227ce4d1bb2d499e17e04d6df,
title = "Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats: Implications for β-amyloid",
abstract = "Epidemiological studies indicated that cigarette smoking protects against the development of several neurodegenerative disorders, including Alzheimer's disease (AD). However, the molecular mechanism(s) underlying this is poorly understood. To gain insight into these protective effects, we used differential display PCR (DD-PCR) to amplify RNA from various brain regions of rats self-administering (SA) nicotine compared with yoked-saline controls. We found that the transthyretin (TTR) gene, whose product has been shown to bind to amyloid β (Aβ) protein and prevent Aβ aggregation, was more abundantly expressed (~1.5- to 2.0-fold) in the brainstem and hippocampus (areas containing choroid plexus) of nicotine SA rats. Subsequently, quantitative reverse transcription-PCR analysis confirmed these DD-PCR findings and demonstrated that nicotine increased TTR mRNA levels in these regions in a time- and dose-dependent manner. Significantly higher TTR protein concentrations were also detected in the ventricular CSF of nicotine- treated rats. In contrast, no differences either in plasma TTR or in CSF and plasma retinol-binding protein were detected. Immunohistochemical analysis showed that immunoreactive TTR was 41.5{\%} lower in the choroid plexus of nicotine-treated rats compared with the saline controls. On the basis of these data, we speculate that the protective effects of nicotine on the development of AD may be attributable, in part, to the increased biosynthesis and secretion of TTR from the choroid plexus. These findings also point toward new approaches that may take advantage of the potentially novel therapeutic effects of nicotinic agonists in patients with AD.",
author = "Li, {Ming D.} and Kane, {Justin K.} and Matta, {Shannon G.} and Blaner, {William S.} and Burt Sharp",
year = "2000",
month = "2",
day = "15",
language = "English (US)",
volume = "20",
pages = "1318--1323",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "4",

}

TY - JOUR

T1 - Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats

T2 - Implications for β-amyloid

AU - Li, Ming D.

AU - Kane, Justin K.

AU - Matta, Shannon G.

AU - Blaner, William S.

AU - Sharp, Burt

PY - 2000/2/15

Y1 - 2000/2/15

N2 - Epidemiological studies indicated that cigarette smoking protects against the development of several neurodegenerative disorders, including Alzheimer's disease (AD). However, the molecular mechanism(s) underlying this is poorly understood. To gain insight into these protective effects, we used differential display PCR (DD-PCR) to amplify RNA from various brain regions of rats self-administering (SA) nicotine compared with yoked-saline controls. We found that the transthyretin (TTR) gene, whose product has been shown to bind to amyloid β (Aβ) protein and prevent Aβ aggregation, was more abundantly expressed (~1.5- to 2.0-fold) in the brainstem and hippocampus (areas containing choroid plexus) of nicotine SA rats. Subsequently, quantitative reverse transcription-PCR analysis confirmed these DD-PCR findings and demonstrated that nicotine increased TTR mRNA levels in these regions in a time- and dose-dependent manner. Significantly higher TTR protein concentrations were also detected in the ventricular CSF of nicotine- treated rats. In contrast, no differences either in plasma TTR or in CSF and plasma retinol-binding protein were detected. Immunohistochemical analysis showed that immunoreactive TTR was 41.5% lower in the choroid plexus of nicotine-treated rats compared with the saline controls. On the basis of these data, we speculate that the protective effects of nicotine on the development of AD may be attributable, in part, to the increased biosynthesis and secretion of TTR from the choroid plexus. These findings also point toward new approaches that may take advantage of the potentially novel therapeutic effects of nicotinic agonists in patients with AD.

AB - Epidemiological studies indicated that cigarette smoking protects against the development of several neurodegenerative disorders, including Alzheimer's disease (AD). However, the molecular mechanism(s) underlying this is poorly understood. To gain insight into these protective effects, we used differential display PCR (DD-PCR) to amplify RNA from various brain regions of rats self-administering (SA) nicotine compared with yoked-saline controls. We found that the transthyretin (TTR) gene, whose product has been shown to bind to amyloid β (Aβ) protein and prevent Aβ aggregation, was more abundantly expressed (~1.5- to 2.0-fold) in the brainstem and hippocampus (areas containing choroid plexus) of nicotine SA rats. Subsequently, quantitative reverse transcription-PCR analysis confirmed these DD-PCR findings and demonstrated that nicotine increased TTR mRNA levels in these regions in a time- and dose-dependent manner. Significantly higher TTR protein concentrations were also detected in the ventricular CSF of nicotine- treated rats. In contrast, no differences either in plasma TTR or in CSF and plasma retinol-binding protein were detected. Immunohistochemical analysis showed that immunoreactive TTR was 41.5% lower in the choroid plexus of nicotine-treated rats compared with the saline controls. On the basis of these data, we speculate that the protective effects of nicotine on the development of AD may be attributable, in part, to the increased biosynthesis and secretion of TTR from the choroid plexus. These findings also point toward new approaches that may take advantage of the potentially novel therapeutic effects of nicotinic agonists in patients with AD.

UR - http://www.scopus.com/inward/record.url?scp=0034652323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034652323&partnerID=8YFLogxK

M3 - Article

C2 - 10662821

AN - SCOPUS:0034652323

VL - 20

SP - 1318

EP - 1323

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 4

ER -