Journal: Journal of Translational Medicine

Article Title: Intranasally administered muse cells attenuate neurodegeneration in Parkinson’s disease

doi: 10.1186/s12967-025-07401-6

Figure Lengend Snippet: Muse cell has protective effects on DA neurons. A : (200×magnification) Compared to normal WT mice, the PBS group showed reduced TH and NeuN staining in the SNc region. In contrast to the PBS group, the muse group exhibited a higher number of TH-positive cells and NeuN-positive cells, with PKH26-labeled muse cells present in the region. Compared to the muse group, the muse + J and non-muse groups displayed relatively fewer TH-positive cells( n = 6). B : S1P expression in the brain tissue of A53T mice (PBS group) was significantly increased compared with normal WT mice. In the group treated with muse cells, S1P expression was markedly reduced relative to both the PBS and non-muse groups, though it remained higher than that in normal WT mice. Western blot results indicated: TNF-α expression in the brains of the PBS group was significantly higher than in control. Compared to the PBS group, TNF-α expression was significantly reduced in the muse group, while the non-muse and muse + J groups also showed reduced TNF-α expression. TNF-α expression in the muse group was lower than in the non-muse and muse + J groups. Expression levels of BDNF and GDNF showed a marked decline in the PBS group. No significant change was seen with non-muse cell treatment, whereas the muse group displayed elevated expression. The expression remained unchanged in the muse + J group. (*Compared to the control group, ** P < 0.01, and compared to the PBS group, # P < 0.05, ## P < 0.01, & compared to the muse group, & P < 0.05) ( n = 3). C : The H&E staining results (200× magnification) showed that in the substantia nigra region of normal WT mice, the tissue structure was normal, and the cell nuclei were clearly visible (red arrows indicate astrocytes, green arrows indicate neuronal cells). In contrast, the brains of PBS group mice exhibited significant neuronal loss, with abnormal neuronal nuclear morphology and blurred boundaries. The non-muse group and muse + J group showed similar conditions to the PBS group, but the degree of neuronal damage was reduced. In the muse group, the number of damaged neurons was significantly decreased, and the tissue characteristics were similar to those of normal WT mice. (red→astrocyte, green→neuronal cells, black→damaged neuronal cells) ( n = 6)

Article Snippet: GDNF Polyclonal antibody , 26179-1-AP , Proteintech.

Techniques: Staining, Labeling, Expressing, Western Blot, Control

Journal: Journal of Neurochemistry

Article Title: Phosphodiesterase Inhibition Increases Striatal GDNF and Protects Against Preclinical Parkinsonism

doi: 10.1111/jnc.70321

Figure Lengend Snippet: Phosphodiesterase inhibition regulates Gdnf expression in striatal parvalbumin interneurons via cAMP signaling. (a) Schematic of the cAMP/PKA/CREB signaling pathway regulating Gdnf expression in striatal parvalbumin (PV) interneurons. AC, adenylyl cyclase; CRE/CREB, cAMP response element/(binding protein); GPCR, G protein‐coupled receptor; Gs/Gi, stimulatory/inhibitory G protein. (b) Relative gene expression (log 2 ) of phosphodiesterase (PDE) in striatal PV interneurons, showing PDE targets of the tested inhibitors: PF05180999 (PF05), Cilostamide (CILO), Roflumilast (ROFLU), and Ibudilast (IBU). (c–i) Ex vivo and in vivo analysis of striatal Gdnf mRNA and GDNF protein after pharmacological treatments. (c) dbcAMP (1 mM) significantly increases Gdnf mRNA ( n = 11 striata per condition). (d) CILO (PDE3 inhibitor) has no significant effect at 0.5–50 μM ( n = 4–6 striata per condition). (e) Ex vivo data showed that ROFLU (PDE4 inhibitor) enhances Gdnf at 25 μM ( n = 15, 6, 11, and 4 striata, respectively), but (f) in vivo ROFLU administration (1 mg/kg, i.p.) showed no effect on Gdnf expression ( n = 4 animals per group). (g) PF05 (PDE2A inhibitor) significantly elevates Gdnf expression ex vivo in a dose‐dependent manner ( n = 6 striata per condition). (h) Co‐treatment with tetrodotoxin (TTX) still increases Gdnf , suggesting a direct effect on PV interneurons ( n = 4–6 striata per condition). (i) Gdnf mRNA expression measured in the striatum 4‐ and 8‐h after the administration of PF05 (10 mg/kg) in vivo ( n = 10, 14, 9 and 13 animals, respectively). Statistical significance ( p ‐values) is indicated in the bar graphs. Data are presented as mean ± SEM, with individual data points shown. Error bars indicate SEM. Statistical tests used: Two‐tailed Student's t ‐test (c, i), or paired t ‐test (g), or one‐way ANOVA with Tukey's post hoc test (d, e, f, h).

Article Snippet: The TaqMan probes used in this study were Gdnf (Mm00599849_m1), Hmbs (Mm00660262_g1), Fos (Mm00487425_m1), and Actb (Mm01205647_g1).

Techniques: Inhibition, Expressing, Binding Assay, Gene Expression, Ex Vivo, In Vivo, Two Tailed Test

Journal: Journal of Neurochemistry

Article Title: Phosphodiesterase Inhibition Increases Striatal GDNF and Protects Against Preclinical Parkinsonism

doi: 10.1111/jnc.70321

Figure Lengend Snippet: Ibudilast (IBU) increases striatal Gdnf mRNA expression ex vivo and in vivo. (a) Dose‐dependent upregulation of Gdnf mRNA in ex vivo striatal slices treated with increasing concentrations (2–50 μM) of Ibudilast ( n = 19, 5, 2, 5, 9, and 6 striata, respectively). (b) Gdnf induction by Ibudilast (50 μM) is reduced by 1 μM tetrodotoxin (TTX), indicating partial activity dependence ( n = 10–12 striata per condition). (c) The CREB inhibitor 666‐15 reduces IBU‐induced Gdnf , implicating CREB in the response ( n = 5–6 striata per condition). (d) A single intraperitoneal (i.p.) injection of IBU (10 mg/kg) rapidly and transiently induces Fos mRNA expression in the mouse striatum ( n = 5 animals per group). (e) In vivo Ibudilast administration (10 mg/kg, i.p.) increases striatal Gdnf mRNA levels ( n = 8–10). (f) A trend toward increased GDNF protein levels is observed in the striatum following in vivo Ibudilast treatment, although not statistically significant ( n = 3–4). Bars represent mean ± SEM; individual dots represent biological replicates. Statistical tests used: One‐way ANOVA with Tukey's post hoc test (a–d) and two‐tailed Student's t ‐test (e, f). Significant p ‐values are shown in the graphs.

Article Snippet: The TaqMan probes used in this study were Gdnf (Mm00599849_m1), Hmbs (Mm00660262_g1), Fos (Mm00487425_m1), and Actb (Mm01205647_g1).

Techniques: Expressing, Ex Vivo, In Vivo, Activity Assay, Injection, Two Tailed Test