Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Paula M Canas; João M N Duarte; Ricardo J Rodrigues; Attila Köfalvi; Rodrigo A Cunha

doi:10.1016/j.neurobiolaging.2008.01.003

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Paula M Canas, João M N Duarte, Ricardo J Rodrigues, Attila Köfalvi, Rodrigo A Cunha

University of Coimbra

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

Abstract

Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A(1) and CB(1) receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A(2A) receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory presynaptic modulation systems.

Original language	English
Pages (from-to)	1877-84
Journal	Neurobiology of Aging
Volume	30
Issue number	11
DOIs	https://doi.org/10.1016/j.neurobiolaging.2008.01.003
Publication status	Published - 2009 Nov
Externally published	Yes

Free keywords

Age Factors
Aging/physiology
Animals
Gene Expression Regulation/physiology
Hippocampus/cytology
Male
Presynaptic Terminals/metabolism
Rats
Receptor, Adenosine A2A/metabolism
Receptor, Cannabinoid, CB1/metabolism
Receptors, Purinergic P2/metabolism
Receptors, Purinergic P2Y1
Synaptophysin/metabolism
Synaptosomal-Associated Protein 25/metabolism
Vesicular Acetylcholine Transport Proteins/metabolism
Vesicular Glutamate Transport Protein 1/metabolism
Vesicular Glutamate Transport Protein 2/metabolism
Vesicular Inhibitory Amino Acid Transport Proteins/metabolism

Access to Document

10.1016/j.neurobiolaging.2008.01.003

Cite this

@article{9b3ac988885740949ed79a82b9bd362a,

title = "Modification upon aging of the density of presynaptic modulation systems in the hippocampus",

abstract = "Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A(1) and CB(1) receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A(2A) receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory presynaptic modulation systems.",

keywords = "Age Factors, Aging/physiology, Animals, Gene Expression Regulation/physiology, Hippocampus/cytology, Male, Presynaptic Terminals/metabolism, Rats, Receptor, Adenosine A2A/metabolism, Receptor, Cannabinoid, CB1/metabolism, Receptors, Purinergic P2/metabolism, Receptors, Purinergic P2Y1, Synaptophysin/metabolism, Synaptosomal-Associated Protein 25/metabolism, Vesicular Acetylcholine Transport Proteins/metabolism, Vesicular Glutamate Transport Protein 1/metabolism, Vesicular Glutamate Transport Protein 2/metabolism, Vesicular Inhibitory Amino Acid Transport Proteins/metabolism",

author = "Canas, {Paula M} and Duarte, {Jo{\~a}o M N} and Rodrigues, {Ricardo J} and Attila K{\"o}falvi and Cunha, {Rodrigo A}",

year = "2009",

month = nov,

doi = "10.1016/j.neurobiolaging.2008.01.003",

language = "English",

volume = "30",

pages = "1877--84",

journal = "Neurobiology of Aging",

issn = "1558-1497",

publisher = "Elsevier",

number = "11",

}

TY - JOUR

T1 - Modification upon aging of the density of presynaptic modulation systems in the hippocampus

AU - Canas, Paula M

AU - Duarte, João M N

AU - Rodrigues, Ricardo J

AU - Köfalvi, Attila

AU - Cunha, Rodrigo A

PY - 2009/11

Y1 - 2009/11

N2 - Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A(1) and CB(1) receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A(2A) receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory presynaptic modulation systems.

AB - Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A(1) and CB(1) receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A(2A) receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory presynaptic modulation systems.

KW - Age Factors

KW - Aging/physiology

KW - Animals

KW - Gene Expression Regulation/physiology

KW - Hippocampus/cytology

KW - Male

KW - Presynaptic Terminals/metabolism

KW - Rats

KW - Receptor, Adenosine A2A/metabolism

KW - Receptor, Cannabinoid, CB1/metabolism

KW - Receptors, Purinergic P2/metabolism

KW - Receptors, Purinergic P2Y1

KW - Synaptophysin/metabolism

KW - Synaptosomal-Associated Protein 25/metabolism

KW - Vesicular Acetylcholine Transport Proteins/metabolism

KW - Vesicular Glutamate Transport Protein 1/metabolism

KW - Vesicular Glutamate Transport Protein 2/metabolism

KW - Vesicular Inhibitory Amino Acid Transport Proteins/metabolism

U2 - 10.1016/j.neurobiolaging.2008.01.003

DO - 10.1016/j.neurobiolaging.2008.01.003

M3 - Article

C2 - 18304697

SN - 1558-1497

VL - 30

SP - 1877

EP - 1884

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 11

ER -

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Abstract

Free keywords

Access to Document

Fingerprint

Cite this