MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum

Injection of MPP+ into the substantia nigra causes extensive necrosis and anterograde degeneration of pars compacta dopaminergic neurons. We studied secondary effects in the ipsilateral striatum by examining dopaminergic terminals, signs of neuronal damage, and glial reactivity at 1, 2, 3, and 7 day...

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Main Authors: Anna M. Canudas, Bibiana Friguls, Anna M. Planas, Cecı´lia Gabriel, Elena Escubedo, Jordi Camarasa, Antoni Camins, Mercè Pallàs
Format: Article
Language:English
Published: Elsevier 2000-08-01
Series:Neurobiology of Disease
Subjects:
rat
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996100903085
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spelling doaj-dc2977ac57f54d1995860000a7b2f5b42021-03-20T04:46:31ZengElsevierNeurobiology of Disease1095-953X2000-08-0174343361MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral StriatumAnna M. Canudas0Bibiana Friguls1Anna M. Planas2Cecı´lia Gabriel3Elena Escubedo4Jordi Camarasa5Antoni Camins6Mercè Pallàs7Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028, Barcelona; Departament de Farmacologia i Toxicologia, IIBB-CSIC, IDIBAPS, Jordi Girona 18-26, 08034, Barcelona, SpainInjection of MPP+ into the substantia nigra causes extensive necrosis and anterograde degeneration of pars compacta dopaminergic neurons. We studied secondary effects in the ipsilateral striatum by examining dopaminergic terminals, signs of neuronal damage, and glial reactivity at 1, 2, 3, and 7 days after injection of MPP+ into the substantia nigra. Dopaminergic terminals and uptake sites were evaluated with [3H]GBR-12935 binding and tyrosine hydroxylase immunoreactivity. Glial reaction was examined with markers of astrocytes and microglia. Stereology was used to evaluate any changes in neuronal density. Tyrosine hydroxylase immunoreactivity and [3H]GBR-12935 binding markedly decreased (74%) from days 2 to 7. Loss of dopaminergic terminals in the ipsilateral striatum was accompanied by an intense astroglial and, to a lesser extent, microglial reaction. However, no signs of cell damage, neuronal loss, or disruption of the blood–brain barrier were found in the striatum. Resident astroglial and microglial cells showed a morphological shift and notable changes in protein expression typical of glial reactivity, yet the presence of macrophage-like cells was not detected. This study shows that injection of MPP+ in the substantia nigra causes a secondary reaction within the ipsilateral striatum involving the transformation of quiescent glia to reactive glia. It is suggested that stimuli derived from damaged dopaminergic terminals within the striatum are able to activate resident glia and that this glial transformation may promote repair and regeneration.http://www.sciencedirect.com/science/article/pii/S0969996100903085reactive glia[3H]PK 11195bindingimmunohistochemistryrat
collection DOAJ
language English
format Article
sources DOAJ
author Anna M. Canudas
Bibiana Friguls
Anna M. Planas
Cecı´lia Gabriel
Elena Escubedo
Jordi Camarasa
Antoni Camins
Mercè Pallàs
spellingShingle Anna M. Canudas
Bibiana Friguls
Anna M. Planas
Cecı´lia Gabriel
Elena Escubedo
Jordi Camarasa
Antoni Camins
Mercè Pallàs
MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum
Neurobiology of Disease
reactive glia
[3H]PK 11195
binding
immunohistochemistry
rat
author_facet Anna M. Canudas
Bibiana Friguls
Anna M. Planas
Cecı´lia Gabriel
Elena Escubedo
Jordi Camarasa
Antoni Camins
Mercè Pallàs
author_sort Anna M. Canudas
title MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum
title_short MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum
title_full MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum
title_fullStr MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum
title_full_unstemmed MPP+ Injection into Rat Substantia Nigra Causes Secondary Glial Activation but Not Cell Death in the Ipsilateral Striatum
title_sort mpp+ injection into rat substantia nigra causes secondary glial activation but not cell death in the ipsilateral striatum
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2000-08-01
description Injection of MPP+ into the substantia nigra causes extensive necrosis and anterograde degeneration of pars compacta dopaminergic neurons. We studied secondary effects in the ipsilateral striatum by examining dopaminergic terminals, signs of neuronal damage, and glial reactivity at 1, 2, 3, and 7 days after injection of MPP+ into the substantia nigra. Dopaminergic terminals and uptake sites were evaluated with [3H]GBR-12935 binding and tyrosine hydroxylase immunoreactivity. Glial reaction was examined with markers of astrocytes and microglia. Stereology was used to evaluate any changes in neuronal density. Tyrosine hydroxylase immunoreactivity and [3H]GBR-12935 binding markedly decreased (74%) from days 2 to 7. Loss of dopaminergic terminals in the ipsilateral striatum was accompanied by an intense astroglial and, to a lesser extent, microglial reaction. However, no signs of cell damage, neuronal loss, or disruption of the blood–brain barrier were found in the striatum. Resident astroglial and microglial cells showed a morphological shift and notable changes in protein expression typical of glial reactivity, yet the presence of macrophage-like cells was not detected. This study shows that injection of MPP+ in the substantia nigra causes a secondary reaction within the ipsilateral striatum involving the transformation of quiescent glia to reactive glia. It is suggested that stimuli derived from damaged dopaminergic terminals within the striatum are able to activate resident glia and that this glial transformation may promote repair and regeneration.
topic reactive glia
[3H]PK 11195
binding
immunohistochemistry
rat
url http://www.sciencedirect.com/science/article/pii/S0969996100903085
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