Poul Henning Jensen

α-Synuclein Vaccination Prevents the Accumulation of Parkinson Disease-Like Pathologic Inclusions in Striatum in Association With Regulatory T Cell Recruitment in a Rat Model

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α-Synuclein Vaccination Prevents the Accumulation of Parkinson Disease-Like Pathologic Inclusions in Striatum in Association With Regulatory T Cell Recruitment in a Rat Model. / Sanchez-Guajardo, Vanesa; Annibali, Ambra; Jensen, Poul Henning; Romero-Ramos, Marina.

In: Journal of Neuropathology and Experimental Neurology, Vol. 72, No. 7, 07.2013, p. 624-45.

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@article{7a1d4d45433c4815af037de38b5854ba,
title = "α-Synuclein Vaccination Prevents the Accumulation of Parkinson Disease-Like Pathologic Inclusions in Striatum in Association With Regulatory T Cell Recruitment in a Rat Model",
abstract = "Human leukocyte antigen-DR induction and lymphocyte infiltrates in the brains of patients with Parkinson disease (PD) and the presence in serum of α-synuclein (α-syn)-specific antibodies suggest that the peripheral immune system may have an active role in the progression of PD. We designed a vaccination strategy to attempt to control these processes and mediate protection against disease progression in a rat PD model. Using a recombinant adeno-associated viral vector, we unilaterally overexpressed human α-syn in the rat substantia nigra to induce a progressive neuropathologic process. Prior to stereotactic delivery of the viral vector, animals were vaccinated with recombinant α-syn (asyn). This resulted in a high-titer anti-α-syn antibody response on α-syn overexpression; the accumulation of CD4-positive, MHC II-positive ramified microglia in the substantia nigra; long-lasting infiltration of CD4-positive, Foxp3-positive cells throughout the nigrostriatal system; and fewer pathologic aggregates in the striatum versus control animals that had received a mock vaccine. A long-term increase in GDNF levels in the striatum and IgG deposition in α-syn-overexpressing cells and neurites in the substantia nigra were also observed. Together, these results suggest that a protective vaccination strategy results in induction of regulatory T cells and distinctly activated microglia, and that this can induce immune tolerance against α-syn.",
author = "Vanesa Sanchez-Guajardo and Ambra Annibali and Jensen, {Poul Henning} and Marina Romero-Ramos",
year = "2013",
month = "7",
doi = "10.1097/NEN.0b013e31829768d2",
language = "English",
volume = "72",
pages = "624--45",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
publisher = "Oxford University Press",
number = "7",

}

RIS

TY - JOUR

T1 - α-Synuclein Vaccination Prevents the Accumulation of Parkinson Disease-Like Pathologic Inclusions in Striatum in Association With Regulatory T Cell Recruitment in a Rat Model

AU - Sanchez-Guajardo, Vanesa

AU - Annibali, Ambra

AU - Jensen, Poul Henning

AU - Romero-Ramos, Marina

PY - 2013/7

Y1 - 2013/7

N2 - Human leukocyte antigen-DR induction and lymphocyte infiltrates in the brains of patients with Parkinson disease (PD) and the presence in serum of α-synuclein (α-syn)-specific antibodies suggest that the peripheral immune system may have an active role in the progression of PD. We designed a vaccination strategy to attempt to control these processes and mediate protection against disease progression in a rat PD model. Using a recombinant adeno-associated viral vector, we unilaterally overexpressed human α-syn in the rat substantia nigra to induce a progressive neuropathologic process. Prior to stereotactic delivery of the viral vector, animals were vaccinated with recombinant α-syn (asyn). This resulted in a high-titer anti-α-syn antibody response on α-syn overexpression; the accumulation of CD4-positive, MHC II-positive ramified microglia in the substantia nigra; long-lasting infiltration of CD4-positive, Foxp3-positive cells throughout the nigrostriatal system; and fewer pathologic aggregates in the striatum versus control animals that had received a mock vaccine. A long-term increase in GDNF levels in the striatum and IgG deposition in α-syn-overexpressing cells and neurites in the substantia nigra were also observed. Together, these results suggest that a protective vaccination strategy results in induction of regulatory T cells and distinctly activated microglia, and that this can induce immune tolerance against α-syn.

AB - Human leukocyte antigen-DR induction and lymphocyte infiltrates in the brains of patients with Parkinson disease (PD) and the presence in serum of α-synuclein (α-syn)-specific antibodies suggest that the peripheral immune system may have an active role in the progression of PD. We designed a vaccination strategy to attempt to control these processes and mediate protection against disease progression in a rat PD model. Using a recombinant adeno-associated viral vector, we unilaterally overexpressed human α-syn in the rat substantia nigra to induce a progressive neuropathologic process. Prior to stereotactic delivery of the viral vector, animals were vaccinated with recombinant α-syn (asyn). This resulted in a high-titer anti-α-syn antibody response on α-syn overexpression; the accumulation of CD4-positive, MHC II-positive ramified microglia in the substantia nigra; long-lasting infiltration of CD4-positive, Foxp3-positive cells throughout the nigrostriatal system; and fewer pathologic aggregates in the striatum versus control animals that had received a mock vaccine. A long-term increase in GDNF levels in the striatum and IgG deposition in α-syn-overexpressing cells and neurites in the substantia nigra were also observed. Together, these results suggest that a protective vaccination strategy results in induction of regulatory T cells and distinctly activated microglia, and that this can induce immune tolerance against α-syn.

U2 - 10.1097/NEN.0b013e31829768d2

DO - 10.1097/NEN.0b013e31829768d2

M3 - Journal article

C2 - 23771222

VL - 72

SP - 624

EP - 645

JO - Journal of Neuropathology and Experimental Neurology

JF - Journal of Neuropathology and Experimental Neurology

SN - 0022-3069

IS - 7

ER -