Publications by authors named "Sibilla Sander"

2 Publications

  • Page 1 of 1

Selective targeting of striatal parvalbumin-expressing interneurons for transgene delivery.

J Neurosci Methods 2021 Apr 27;354:109105. Epub 2021 Feb 27.

Laboratory of Cellular and Molecular Neurotherapies, Center for Neuroscience Research, Clinical Neurosciences Department, Lausanne University Hospital, Switzerland. Electronic address:

PV mice--> combined with AAV-FLEX vectors allowed efficient and specific targeting of PV interneurons in the striatum. However, diffusion of viral particles to the globus pallidus caused massive transduction of PV projection neurons and subsequent anterograde transport of the transgene product to the subthalamic nucleus and the substantia nigra pars reticulata. Different AAV serotypes (1 and 9) and promoters (CBA and human synapsin) were evaluated. The combination of AAV1, a moderate expression level (human synapsin promoter) and a precise adjustment of the stereotaxic coordinates in the anterior and dorsolateral part of the striatum were necessary to avoid transduction of PV GP projection neurons. Even in the absence of direct transduction due to diffusion of viral particles, GP PV projection neurons could be retrogradely transduced via their terminals present in the dorsal striatum. However, in the absence of diffusion, GP-Str PV projection neurons were poorly or not transduced suggesting that retrograde transduction did not significantly impair the selective targeting of striatal PV neurons. Finally, a prominent reduction of the number of striatal PV interneurons (about 50 %) was evidenced in the presence of the Cre recombinase suggesting that functional effects of AAV-mediated transgene expression in PV striatal interneurons in PV mice should be analyzed with caution.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109105DOI Listing
April 2021

GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease.

J Clin Med 2020 Feb 7;9(2). Epub 2020 Feb 7.

Laboratory of Molecular Neurotherapies and NeuroModulation, Center for Neuroscience Research, Lausanne University Hospital, CHUV-Pavillon 3, av de Beaumont, CH-1010 Lausanne, Switzerland.

In a healthy adult brain, glial cell line-derived neurotrophic factor (GDNF) is exclusively expressed by neurons, and, in some instances, it has also been shown to derive from a single neuronal subpopulation. Secreted GDNF acts in a paracrine fashion by forming a complex with the GDNF family receptor α1 (GFRα1), which is mainly expressed by neurons and can act in as a membrane-bound factor or in as a soluble factor. The GDNF/GFRα1 complex signals through interactions with the "rearranged during transfection" (RET) receptor or via the neural cell adhesion molecule (NCAM) with a lower affinity. GDNF can also signal independently from GFRα1 by interacting with syndecan-3. RET, which is expressed by neurons involved in several pathways (nigro-striatal dopaminergic neurons, motor neurons, enteric neurons, sensory neurons, etc.), could be the main determinant of the specificity of GDNF's pro-survival effect. In an injured brain, de novo expression of GDNF occurs in glial cells. Neuroinflammation has been reported to induce GDNF expression in activated astrocytes and microglia, infiltrating macrophages, nestin-positive reactive astrocytes, and neuron/glia (NG2) positive microglia-like cells. This disease-related GDNF overexpression can be either beneficial or detrimental depending on the localization in the brain and the level and duration of glial cell activation. Some reports also describe the upregulation of RET and GFRα1 in glial cells, suggesting that GDNF could modulate neuroinflammation.
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http://dx.doi.org/10.3390/jcm9020456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073520PMC
February 2020