scholarly journals Effects of ex vivo transduction of mesencephalic reaggregates with bcl-2 on grafted dopamine neuron survival

2007 ◽  
Vol 1134 ◽  
pp. 33-44 ◽  
Author(s):  
Caryl E. Sortwell ◽  
William J. Bowers ◽  
Scott E. Counts ◽  
Mark R. Pitzer ◽  
Matthew F. Fleming ◽  
...  
1998 ◽  
Vol 813 (2) ◽  
pp. 313-322 ◽  
Author(s):  
Günter U Höglinger ◽  
Jürgen Sautter ◽  
Morten Meyer ◽  
Christian Spenger ◽  
Rolf W Seiler ◽  
...  

2006 ◽  
Vol 1099 (1) ◽  
pp. 199-205 ◽  
Author(s):  
J.S. Schneider ◽  
K.A. Bradbury ◽  
Yoshihiro Anada ◽  
Jin-ichi Inokuchi ◽  
D.W. Anderson

2001 ◽  
Vol 168 (1) ◽  
pp. 183-191 ◽  
Author(s):  
Edward D. Clarkson ◽  
W.Michael Zawada ◽  
K.Pat Bell ◽  
James E. Esplen ◽  
Paul K. Choi ◽  
...  

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Peng Zhong ◽  
Casey R Vickstrom ◽  
Xiaojie Liu ◽  
Ying Hu ◽  
Laikang Yu ◽  
...  

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors.


2020 ◽  
Vol 4 (s1) ◽  
pp. 1-1
Author(s):  
Shaheen Farhadi ◽  
Adithya Gopinath ◽  
Wolfgang Streit ◽  
Gregory A Hudalla ◽  
Habibeh Khoshbouei

OBJECTIVES/GOALS: Develop a strategy to restrict GDNF diffusion at an injected CNS tissue site for dopamine neuron rescue by endowing it with binding affinity for carbohydrates that are abundant on the cell surface and extracellular matrix. METHODS/STUDY POPULATION: GDNF will be fused to galectin-3 (G3), a human protein that binds to β-galactoside residues of cell surface and matrix glycoproteins. We characterized the binding of G3 fusion proteins to various glycoproteins and primary human myeloid cells. We incubated G3 fusions with CNS tissue ex vivo to measure their binding and depth of penetration via diffusion. We next plan to administer GDNF-G3 via CNS intracranial infusion in a murine PD model and then conduct behavioral PD phenotype testing via rotarod and pole descent to compare to non-parkinsonian controls. We will further examine the effects of GDNF-G3 on degeneration using immunohistochemical examination of post-mortem brain tissue. RESULTS/ANTICIPATED RESULTS: Based on results from previous clinical trials of GDNF delivery, we anticipate that a successful intervention using GDNF-G3 will result in rescue of midbrain dopaminergic neurons in a murine PD model. In murine CNS tissue, we observed binding to glycans at the tissue surfaces when incubated with G3 fusion proteins ex vivo, suggesting GDNF-G3 will remain localized to the injection site. Next we will administer GDNF-G3 via CNS intracranial infusion in a murine PD model and assess efficacy by behavior and histopathology. GDNF-G3-mediated dopamine neuron rescue are expected to slow or reverse the progression of PD in these animal models. DISCUSSION/SIGNIFICANCE OF IMPACT: PD treatments focus on symptomatic relief. Standard therapies have not been efficacious in rescuing of dopaminergic neurons. GDNF-G3 administered at the site of neurodegeneration would represent a milestone on the path to treating PD pathology and address limitations of GDNF delivery.


Cell ◽  
2018 ◽  
Vol 174 (6) ◽  
pp. 1436-1449.e20 ◽  
Author(s):  
Celine I. Maeder ◽  
Jae-Ick Kim ◽  
Xing Liang ◽  
Konstantin Kaganovsky ◽  
Ao Shen ◽  
...  

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