Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy

Zhao, Zhongqiu; Alam, Md. Sayem; Oppenheim, Ronald W.; Prevette, David; Evenson, Ariana; Parsadanian, Alexander

doi:10.1016/j.expneurol.2004.06.015

Cited by 103 publications

(87 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This degree of enhancement is similar to the three-fold increase in β-cell mass observed in other growth factor overexpression studies, including PTH-RP and placental lactogen 20,21 . It is important to note that the effects of GDNF on β-cells is not a systemic effect as serum GDNF levels have been measured in GDNF-tg mice and are no different from littermate controls 10 .…”

Section: Discussionmentioning

confidence: 99%

“…In vivo studies were conducted in littermates obtained from crossing CF1 WT mice with GFAP-GDNF transgenic mice on a CF1 background generated at Washington University, in St. Louis, MO, U.S.A. GFAP-GDNF transgenic mice are engineered to overexpress GDNF in glial cells under the control of the glial fibrillary acidic protein promoter 10 . The genotypes of the mice were determined by PCR using DNA extracted from mouse tail using the REDExtract-N-Amp Tissue PCR Kit (Sigma-Aldrich CO, St. Louis, MO, USA) according to recommended procedure.…”

Section: Animalsmentioning

confidence: 99%

“…Having demonstrated the effects of GDNF in vitro we next examined the effects of GDNF in vivo using a GDNF transgenic (GDNF-tg) mouse in which the overexpression of GDNF has been demonstrated in astrocytes in the brain and spinal cord 10 Despite their lower body weights, GDNF-tg mice have normal eye opening, fur growth, and weaning and reproductive capacity, similar to WT mice. GDNF-tg mice have a slight tremor at birth that disappears by 2-3 Weeks of age.…”

Section: Mice Overexpressing Gdnf In Pancreatic Glia Have Higher β-Cementioning

confidence: 99%

See 2 more Smart Citations

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Mice Overexpressing Gdnf In Pancreatic Glia Have Higher β-Cementioning

confidence: 99%

See 1 more Smart Citation

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…The importance of using these cells as gene transfer targets to express molecules of therapeutic interest in the CNS for the treatment of neuronal diseases and disorders has recently been demonstrated and discussed. [1][2][3] Neurotrophic factors secreted by astrocytes in the CNS may act locally on nearby neurons and support their functions like those that are produced in a peripheral target region and act through the classical mechanism of retrograde transport. Under the pathological conditions that affect axonal transport, the physiological functions of the neurotrophic factors produced by target tissues will be hampered or even totally blocked.…”

Section: Introductionmentioning

confidence: 99%

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

Wang

2006

Gene Ther

View full text Add to dashboard Cite

Therapeutic gene expression in glial cells has been tested for the treatment of neurological diseases in animal models. Many of such studies used the promoter of the glial fibrillary acidic protein (GFAP) to restrict gene expression to astrocytes. We have investigated in the current study whether it is possible to improve the transcriptional activity of the cellular promoter, while maintaining its cell-type specificity. We constructed an expression cassette containing a hybrid cytomegalovirus (CMV) enhancer/GFAP promoter and placed it into baculovirus vectors, a type of viral vectors capable of transducing astrocytes. In another vector design, we used inverted terminal repeats (ITRs) from adeno-associated virus (AAV) to flank the expression cassette. The recombinant baculoviruses with the hybrid promoter improved gene expression levels over two orders of magnitude in glial cell lines and by 10-fold in the rat brain when compared to the baculoviruses with the GFAP promoter alone. The expression was further improved by ITR flanking, reaching levels higher than that mediated by the baculovirus vectors with the CMV immediate-early enhancer/ promoter (CMV promoter). Using these recombinant baculoviruses, we observed extended in vivo transgene expression in the rat brain at 90 days postinjection, by which time the gene expression from baculovirus vectors with the GFAP or CMV promoter had already become undetectable. The astrocyte specificity of the GFAP promoter was preserved in the engineered expression cassette with the CMV enhancer and the AAV ITRs, as demonstrated by immunohistological analysis of brain samples and an axonal retrograde transport assay. Taken together, our findings suggest that these baculovirus vectors may serve as useful tools for astrocyte-specific gene expression in the brain.

show abstract

“…Thus, astrocytes also play crucial roles in the injury site after TBI, as they exert homeostatic mechanisms critical for maintaining neural circuit function, such as buffering neurotransmitters, modulating extracellular osmolarity, and calibrating neurovascular coupling [55]. Accordingly, astrocytes are thought to exert many beneficial effects post-TBI [56] as providing neurotrophins that support and guide axons in their recovery [57], increasing cell proliferation, and promoting the long-term survival of neurons by inhibiting apoptosis [58,59]. However, when the presence of astrocytes is too large and they become over activated, they may build a dense physical and chemical barrier surrounding the injury site (glial scar), which encapsulates and isolates the axons.…”

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Regner¹,

Meirelles²,

Simon³

2018

Traumatic Brain Injury - Pathobiology, Advanced Diagnostics and Acute Management

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Understanding the pathophysiology of TBI is crucial for the development of more effective therapeutic strategies. At the moment of the traumatic impact, transfer of kinetic forces causes neurologic damage; this primary injury triggers a secondary wave of biochemical cascades, together with metabolic and cellular changes, called secondary neural injury. These areas of ongoing secondary injury, or areas of "traumatic penumbra," represent crucial targets for therapeutic interventions. This chapter is focused on the interplay between progression of parenchymal injury and the neuroprotective and neurorestorative processes that are emerging and developing subsequently to traumatic impact. Thus, we emphasized the role of traumatic penumbra in TBI pathogenesis and suggested a crucial contribution of the neurovascular units (NVUs) and paracrine effects of exosomes and miRNAs in promoting neurological recovery.

show abstract

Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy

Cited by 103 publications

References 77 publications

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Contact Info

Product

Resources

About