The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain

M. Emre; C. Geula; B. J. Ransil; M. M. Mesulam

doi:10.1016/0197-4580(92)90055-3

The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain

M. Emre, C. Geula^*, B. J. Ransil, M. M. Mesulam

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

127 Scopus citations

Abstract

The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (βAP1-40) was studied in rats. A synthetic peptide with the reverse sequence (βAP40-1) or the vehicle alone were injected inthe contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that βAP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. βAP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that βAP 1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.

Original language	English (US)
Pages (from-to)	553-559
Number of pages	7
Journal	Neurobiology of Aging
Volume	13
Issue number	5
DOIs	https://doi.org/10.1016/0197-4580(92)90055-3
State	Published - 1992

Funding

of evidence showinthga tflAP containingd iffusep laquesm ay The peptideas ndthe vehicle used tihne see xperimenwtse rek indly exist in the human brain without necessarilrye sultingin tissue providedb y BruceA . Yankner.T he antibodtyo beta-amyloipdr otein destructioann dthat there may be little correlation between the was a giftf rom DennisS elkoe.W e thankK ristin Bouvea ndChristine extento f mentald eclinei n AD and the postmortemde nsityo f Calabresefo r technicaal ssistanceS.u pportedin part by NIH grants plaques( 6). AG05134,N S20285a, ndAG 10282.

Keywords

Alzheimer disease
Beta-amyloid
Cholinergic system

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Aging
General Neuroscience
Developmental Biology

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10.1016/0197-4580(92)90055-3

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title = "The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain",

abstract = "The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (βAP1-40) was studied in rats. A synthetic peptide with the reverse sequence (βAP40-1) or the vehicle alone were injected inthe contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that βAP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. βAP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that βAP 1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.",

keywords = "Alzheimer disease, Beta-amyloid, Cholinergic system",

author = "M. Emre and C. Geula and Ransil, {B. J.} and Mesulam, {M. M.}",

note = "Funding Information: of evidence showinthga tflAP containingd iffusep laquesm ay The peptideas ndthe vehicle used tihne see xperimenwtse rek indly exist in the human brain without necessarilrye sultingin tissue providedb y BruceA . Yankner.T he antibodtyo beta-amyloipdr otein destructioann dthat there may be little correlation between the was a giftf rom DennisS elkoe.W e thankK ristin Bouvea ndChristine extento f mentald eclinei n AD and the postmortemde nsityo f Calabresefo r technicaal ssistanceS.u pportedin part by NIH grants plaques( 6). AG05134,N S20285a, ndAG 10282.",

year = "1992",

doi = "10.1016/0197-4580(92)90055-3",

language = "English (US)",

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T1 - The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain

AU - Emre, M.

AU - Geula, C.

AU - Ransil, B. J.

AU - Mesulam, M. M.

N1 - Funding Information: of evidence showinthga tflAP containingd iffusep laquesm ay The peptideas ndthe vehicle used tihne see xperimenwtse rek indly exist in the human brain without necessarilrye sultingin tissue providedb y BruceA . Yankner.T he antibodtyo beta-amyloipdr otein destructioann dthat there may be little correlation between the was a giftf rom DennisS elkoe.W e thankK ristin Bouvea ndChristine extento f mentald eclinei n AD and the postmortemde nsityo f Calabresefo r technicaal ssistanceS.u pportedin part by NIH grants plaques( 6). AG05134,N S20285a, ndAG 10282.

PY - 1992

Y1 - 1992

N2 - The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (βAP1-40) was studied in rats. A synthetic peptide with the reverse sequence (βAP40-1) or the vehicle alone were injected inthe contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that βAP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. βAP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that βAP 1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.

AB - The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (βAP1-40) was studied in rats. A synthetic peptide with the reverse sequence (βAP40-1) or the vehicle alone were injected inthe contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that βAP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. βAP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that βAP 1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.

KW - Alzheimer disease

KW - Beta-amyloid

KW - Cholinergic system

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JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 5

ER -

The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain

Abstract

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Keywords

ASJC Scopus subject areas

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