Behavior;
Immunofluorescence;
Motor deficit;
Mouse model;
Parkinson's disease;
Phosphorylation;
Synucleinopathy;
alpha-Synuclein;
Transgene;
FAMILIAL PARKINSONS-DISEASE;
MULTIPLE SYSTEM ATROPHY;
LEWY BODY DISEASE;
AUTOPHAGY PATHWAY;
GROWTH-FACTOR;
B-CHAIN;
MICE;
EXPRESSION;
ERBB4;
ADULT;
D O I:
10.1186/1471-2202-14-6
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Background: Progressive accumulation of alpha-synuclein (alpha-Syn) protein in different brain regions is a hallmark of synucleinopathic diseases, such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. alpha-Syn transgenic mouse models have been developed to investigate the effects of alpha-Syn accumulation on behavioral deficits and neuropathology. However, the onset and progression of pathology in alpha-Syn transgenic mice have not been fully characterized. For this purpose we investigated the time course of behavioral deficits and neuropathology in PDGF-beta human wild type alpha-Syn transgenic mice (D-Line) between 3 and 12 months of age. Results: These mice showed progressive impairment of motor coordination of the limbs that resulted in significant differences compared to non-transgenic littermates at 9 and 12 months of age. Biochemical and immunohistological analyses revealed constantly increasing levels of human alpha-Syn in different brain areas. Human alpha-Syn was expressed particularly in somata and neurites of a subset of neocortical and limbic system neurons. Most of these neurons showed immunoreactivity for phosphorylated human alpha-Syn confined to nuclei and perinuclear cytoplasm. Analyses of the phenotype of alpha-Syn expressing cells revealed strong expression in dopaminergic olfactory bulb neurons, subsets of GABAergic interneurons and glutamatergic principal cells throughout the telencephalon. We also found human alpha-Syn expression in immature neurons of both the ventricular zone and the rostral migratory stream, but not in the dentate gyrus. Conclusion: The present study demonstrates that the PDGF-beta alpha-Syn transgenic mouse model presents with early and progressive accumulation of human alpha-Syn that is accompanied by motor deficits. This information is essential for the design of therapeutical studies of synucleinopathies.
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Harvard Univ, Sch Med, Boston, MA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Clark, Joanne
;
Clore, Elizabeth L.
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Clore, Elizabeth L.
;
Zheng, Kangni
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Zheng, Kangni
;
Adame, Anthony
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Neurosci, Sch Med, San Diego, CA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Adame, Anthony
;
Masliah, Eliezer
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Neurosci, Sch Med, San Diego, CA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Masliah, Eliezer
;
Simon, David K.
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Harvard Univ, Sch Med, Boston, MA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
机构:
Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Crews, Leslie
;
Spencer, Brian
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Spencer, Brian
;
Desplats, Paula
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Desplats, Paula
;
Patrick, Christina
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Patrick, Christina
;
Paulino, Amy
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Paulino, Amy
;
Rockenstein, Edward
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Rockenstein, Edward
;
Hansen, Lawrence
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Hansen, Lawrence
;
Adame, Anthony
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Adame, Anthony
;
Galasko, Douglas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Galasko, Douglas
;
Masliah, Eliezer
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Harvard Univ, Sch Med, Boston, MA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Clark, Joanne
;
Clore, Elizabeth L.
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Clore, Elizabeth L.
;
Zheng, Kangni
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Zheng, Kangni
;
Adame, Anthony
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Neurosci, Sch Med, San Diego, CA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Adame, Anthony
;
Masliah, Eliezer
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Neurosci, Sch Med, San Diego, CA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Masliah, Eliezer
;
Simon, David K.
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
Harvard Univ, Sch Med, Boston, MA USABeth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
机构:
Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Crews, Leslie
;
Spencer, Brian
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Spencer, Brian
;
Desplats, Paula
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Desplats, Paula
;
Patrick, Christina
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Patrick, Christina
;
Paulino, Amy
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Paulino, Amy
;
Rockenstein, Edward
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Rockenstein, Edward
;
Hansen, Lawrence
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Hansen, Lawrence
;
Adame, Anthony
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Adame, Anthony
;
Galasko, Douglas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Galasko, Douglas
;
Masliah, Eliezer
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA