Analysis of brain and spinal cord of treated Gaa−/− mice and controls

Slides:

Advertisements

Similar presentations

Fig. 2. The expression of pKr-2 in the substantia nigra (SN) of patients with Parkinson's disease (PD). (A, B) Western blot analysis for pKr-1-2 and pKr-2,

Advertisements

From: Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis Anesthes. 2017;127(3):

Fig. 6. AZD6738 induces DNA damage and apoptosis and exhibits antitumor efficacy in xenograft models of high-risk medulloblastoma and neuroblastoma. AZD6738.

Fig. 5. Circulating PPi concentration does not correlate with severity of calcification phenotype in mice. Circulating PPi concentration does not correlate.

Fig. 4. Intramuscular injection of AAV9-Cas9/sgRNA-51 corrects dystrophin expression. Intramuscular injection of AAV9-Cas9/sgRNA-51 corrects dystrophin.

Fig. 6. C3 deficiency resulted in partial sparing of neuron loss in hippocampal CA3 in 16-month-old APP/PS1 mice. C3 deficiency resulted in partial sparing.

Fig. 4. Bexarotene promotes PPARδ activation of target genes in mouse brain and muscle. Bexarotene promotes PPARδ activation of target genes in mouse brain.

Fig. 1. BCAS1 expression identifies newly generated oligodendrocytes.

Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain Michelle.

Fig. 5. Wisper is associated with TIA1-related protein and regulates lysyl hydroxylase 2 expression. Wisper is associated with TIA1-related protein and.

Fig. 3. BET inhibition reduces homologous recombination.

MRSA virulence proteins cause LMC death and diminished CLV function

Fig. 1 MT-2 ameliorates asthmatic pulmonary resistance.

Fig. 4 Infection-induced CLV dysfunction is associated with decreased LMC coverage. Infection-induced CLV dysfunction is associated with decreased LMC.

Molecular Therapy - Nucleic Acids

Molecular Therapy - Methods & Clinical Development

Molecular Therapy - Methods & Clinical Development

Fig. 1. Aberrant JNK pathway activation in mouse models of ALS and in spinal cord tissue from patients with sporadic ALS. Aberrant JNK pathway activation.

Immunofluorescence staining of virus-infected human placental explants

Fig. 7 Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors. Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors.

Figure 3 Complete loss of neurofilament light (NEFL) protein in cultured patient neurons Complete loss of neurofilament light (NEFL) protein in cultured.

Fig. 6. Apoptotic MSCs exert in vivo immunosuppression in a TH2-type inflammation model in the absence of cytotoxic cells. Apoptotic MSCs exert in vivo.

Fig. 4. Expression of HGF in liver ECs cooperates with NOX4 inhibition to enhance engraftment of regenerative hepatocytes. Expression of HGF in liver ECs.

Nat. Rev. Mater. doi: /natrevmats

Fig. 7. KIF11 informs patient prognosis, and targeting improves survival in a preclinical model. KIF11 informs patient prognosis, and targeting improves.

Fig. 1. mGlu7 expression is reduced in RTT autopsy samples.

Fig. 1. Neurobehavioral testing in YG8R mice transplanted with wild-type mouse HSPCs. Neurobehavioral testing in YG8R mice transplanted with wild-type.

Fig. 5 Local gel scaffold for T cell memory response.

Fig. 2 Fas controls IL-1RA–sEV secretion in murine MSCs.

Molecular Therapy - Methods & Clinical Development

Fig. 7 Improvement of clinical score and axon pathology by nasal IL-4 treatment during chronic EAE. Improvement of clinical score and axon pathology by.

Molecular Therapy - Methods & Clinical Development

Fig. 4. Loss of DLK expression is neuroprotective in the SOD1G93A mouse model of ALS. Loss of DLK expression is neuroprotective in the SOD1G93A mouse model.

Fig. 1. PGBD5-expressing cells do not tolerate deficiency of nonhomologous end-joining DNA repair. PGBD5-expressing cells do not tolerate deficiency of.

Fig. 5. Nutlin-3 treatment rescues the proliferation and differentiation of NPCs in vitro. Nutlin-3 treatment rescues the proliferation and differentiation.

Fig. 4 TNF-α up-regulates Fas/Fap-1 expression to promote IL-1RA–sEV release in murine MSCs. TNF-α up-regulates Fas/Fap-1 expression to promote IL-1RA–sEV.

Fig. 1. β-APP overexpression or exposure to inflammatory mediators induces sIBM-like pathology in cultured rat myocytes that is abrogated by arimoclomol.

Fig. 3. Morphological changes associated with glial activation were reduced in 16-month-old APP/PS1;C3 KO mice. Morphological changes associated with glial.

Kurt W. Prins et al. BTS 2016;1: T-Tubule Derangements in mdx Mice Are Associated With JPH-2 Misregulation (A) Representative confocal images of.

Fig. 7. Treatment with DLK inhibitors reduces p-c-Jun and protects against neuronal and synaptic loss in vitro and in ALS mouse models. Treatment with.

Fig. 3. VEGFR-3 signaling increases infiltration of naïve T cells in a CCR7-dependent manner. VEGFR-3 signaling increases infiltration of naïve T cells.

Fig. 2. CD31 provides robust NP targeting in vitro but slow kinetics.

Fig. 2 ALRN-6924 rapidly increases transcription at the p21 locus and affects its bursting dynamics. ALRN-6924 rapidly increases transcription at the p21.

Volume 22, Issue 3, Pages (March 2014)

Fig. 3 CSF1 is expressed in human melanoma.

Fig. 4 Spinally grafted iPSC-NPCs show long-term survival and neuronal and glial differentiation in syngeneic recipient in the absence of immunosuppression.

Fig. 2. Cellular response to FolamiRs in vitro.

Fig. 1. Specificity of FolamiR uptake in cancer cells in culture.

Fig. 7. Scale-up of AAV vector–mediated liver gene transfer of secretable GAA to nonhuman primates. Scale-up of AAV vector–mediated liver gene transfer.

Correlation of reovirus RNA/protein with proliferating tumor cells

Fig. 6 Combination therapy with LVSOD2 and LVshCTGF preserves flap volume and reduces fibrosis after RT. Combination therapy with LVSOD2 and LVshCTGF preserves.

Fig. 4 ALRN-6924 inhibits cellular proliferation and clonogenic capacity, and induces cell cycle arrest and apoptosis in AML cell lines. ALRN-6924 inhibits.

Fig. 2. Thorase variants cause impaired GluA2 endocytosis and trafficking in mouse primary cortical neurons. Thorase variants cause impaired GluA2 endocytosis.

Fig. 2. BET inhibition enhances PARPi-induced DNA damage.

Fig. 7 Transient immunosuppression (4 weeks) supports long-term graft survival and is associated with progressive decrease in spinal regional inflammatory.

Fig. 1. In vivo–in vitro validation of [11C]UCB-J as a synaptic density biomarker in the baboon brain. In vivo–in vitro validation of [11C]UCB-J as a synaptic.

Fig. 2. Deficiency of neuronal HS leads to reduced neuroinflammation.

Activation of glial cells.

Global analysis of RV[S/T]F motif phosphorylation during mitosis.

Microglia activation in distinct sites of the spinal cord from mice with bronchial asthma or atopic dermatitis on the back skin at the thoracic spinal.

ASyn overexpression exacerbates the effect of MPP+ on Ca2+ in SN but not VTA neurons. aSyn overexpression exacerbates the effect of MPP+ on Ca2+ in SN.

Astroglial activation in distinct sites of the spinal cord from mice with bronchial asthma or atopic dermatitis on the back skin at the thoracic spinal.

Fig. 3. Morphological changes associated with glial activation were reduced in 16-month-old APP/PS1;C3 KO mice. Morphological changes associated with glial.

Targeting p53-dependent stem cell loss for intestinal chemoprotection

Microfluidic platform for cell phenotype and gene function analysis

Fig. 3. HERV-K–induced neuronal toxicity in vivo.

Fig. 5 C9orf72 knockdown disrupts autophagy induction.

Repulsive Guidance Molecule-a Is Involved in Th17-Cell-Induced Neurodegeneration in Autoimmune Encephalomyelitis Shogo Tanabe, Toshihide Yamashita Cell.

Fig. 3. Col IV–Ac2-26 NPs suppress lesional superoxide and increase lesional Il10 mRNA in Ldlr−/− mice with established atherosclerosis. Col IV–Ac2-26.

Molecular Therapy - Methods & Clinical Development

Presentation transcript:

Fig. 4. Analysis of brain and spinal cord of treated Gaa−/− mice and controls. Analysis of brain and spinal cord of treated Gaa−/− mice and controls. (A to I) Four-month-old mice treated with PBS or AAV8 vectors (2 × 1012 vg/kg) and followed for 3 months (n = 4 to 5 per cohort) or 10 months (n = 8 to 9 per cohort; n = 3 Gaa−/−-PBS). Gaa+/+-PBS, wild-type littermates; Gaa−/−-PBS, untreated control. Western blot analysis of brain (A) and cervical spinal cord (B) lysates 10 months after treatment using a monoclonal anti-GAA antibody. An anti-tubulin antibody was used as loading control. (C) Quantification of glycogen content in brain 3 and 10 months after treatment. The quantification is reported as percentage of glycogen in Gaa−/− mice treated with PBS. (D to I) Analysis of spinal cord 10 months after treatment. (D) Count of choline acetyl transferase–positive (ChAT+) motor neurons (MN) in spinal cord. (E) Representative images of ChAT staining. (F) Count of ionized calcium binding adaptor molecule 1–positive (Iba1+) cells in the gray matter of spinal cord. (G) Representative images of Iba1 staining. (H) Glial fibrillary acidic protein (GFAP) fluorescence quantification in the gray matter of the spinal cord. AU, arbitrary units. (I) Representative images of GFAP staining. In all images, cells were stained with the nuclear marker 4’,6-diamidino-2-phenylindole (DAPI). Scale bars, 200 μm (I, top) and 25 μm (E, G, and I, bottom). (D to I) Gaa−/−-PBS, n = 2; n = 3 for the other cohorts. Error bars represent SD of the mean. Statistical analysis: (C) two-way ANOVA with Tukey’s post hoc (treatment, time); (D, F, and H) two-way ANOVA with Tukey’s post hoc (treatment, region of spinal cord). Francesco Puzzo et al., Sci Transl Med 2017;9:eaam6375 Published by AAAS