Protective effects of BDNF and NT-3 but not PDGF against hypoglycemic injury to cultured striatal neurons

The present study examined the recent report that transplantation of neonatal striatal tissue into kainic acid (KA) lesioned striatum protected the contralateral striatum from a subsequent KA lesion. We did not find a significant difference in the survival rate of animals that received neonatal striatal transplants into a KA lesioned striatum followed by a subsequent lesion of the contralateral striatum compared to those animals that received bilateral KA-induced striatal lesions alone. The tissue transplants did not protect against the degeneration of striatal neurons induced by KA. Indeed, the survival rate was very low (25%) in the transplant groups. A second experiment was also performed to examine whether a neonatal striatal transplant might reduce the severe syndrome of aphagia and adipsia associated with KA lesions of the striatum. Animals that received the neonatal striatal transplants showed increased aphagia and adipsia compared to animals only receiving the KA lesion. Again, the transplant group had a very low survival rate (10%). The present study was unable to confirm that neonatal striatal transplants protect against KA lesions either by themselves or in conjunction with a recent KA lesion.

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Homeoprotein neuroprotection of embryonic neuronal cells

10.1101/695684 ◽

2019 ◽

Author(s):

Stephanie E. Vargas Abonce ◽

Mélanie Leboeuf ◽

Alain Prochiantz ◽

Kenneth L. Moya

Keyword(s):

Oxidative Stress ◽

Ganglion Cells ◽

Neuronal Cells ◽

Neuroprotective Activity ◽

Live Cells ◽

Protective Effects ◽

Striatal Neurons ◽

Dna Breaks ◽

Embryonic Neurons

ABSTRACTMost homeoprotein transcription factors have a highly conserved internalization domain used in intercellular transfer. Internalization of homeoproteins ENGRAILED1 or ENGRAILED2 promotes the survival of adult dopaminergic cells, whereas that of OTX2 protects adult retinal ganglion cells. Here we characterize the in vitro neuroprotective activity of several homeoproteins in response to H2O2. Protection is observed with ENGRAILED1, ENGRAILED2, OTX2, GBX2 and LHX9 on midbrain and striatal embryonic neurons whereas cell-permeable c-MYC shows no protective effects. Therefore, five homeoproteins belonging to 3 different classes (ANTENNAPEDIA, PAIRED and LIM) share the ability to protect embryonic neurons from midbrain and striatum. Because midbrain and striatal neurons do not express the same repertoire of the 4 proteins, a lack of neuronal specificity together with a general protective activity can be proposed. In contrast, hEN1 and GBX2 exerted no protection on non-neuronal cells including mouse embryo fibroblasts, macrophages or HeLa cells. For the 4 proteins, protection against cell-death correlated with a reduction in the number of H2O2-induced DNA break foci in midbrain and striatal neurons. In conclusion, within the limit of the number of cell types and homeoproteins tested, homeoprotein protection against oxidative stress-induced DNA breaks and death is specific to neurons but shows no homeoprotein or neuronal type specificity.SIGNIFICANCE STATEMENTHomeoproteins are DNA binding proteins regulating gene expression throughout life. Many of them transfer between cells and are thus internalized by live cells. This has allowed for their use as therapeutic proteins in animal models of Parkinson disease and glaucoma. Part of their therapeutic activity is through a protection against neuronal death. Here we show that internalized homeoproteins from three different classes protect embryonic ventral midbrain and striatal neurons from oxidative stress, both at the level of DNA damage and survival. The interest of this finding is that it lends weight to the possibility that many homeoproteins play a role in neuroprotection through shared mechanisms involving, in particular, DNA protection against stress-induced breaks.

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Astrocytes from cortex and striatum show differential responses to mitochondrial toxin and BDNF: implications for protection of striatal neurons expressing mutant huntingtin

Journal of Neuroinflammation ◽

10.1186/s12974-020-01965-4 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Julieta Saba ◽

Federico López Couselo ◽

Juan Turati ◽

Lila Carniglia ◽

Daniela Durand ◽

...

Keyword(s):

Transforming Growth Factor ◽

Therapeutic Potential ◽

Significant Heterogeneity ◽

Protective Effects ◽

Mutant Huntingtin ◽

Cellular Model ◽

Striatal Neurons ◽

Cortical Astrocytes ◽

Mitochondrial Toxin

Abstract Background Evidence shows significant heterogeneity in astrocyte gene expression and function. We previously demonstrated that brain-derived neurotrophic factor (BDNF) exerts protective effects on whole brain primary cultured rat astrocytes treated with 3-nitropropionic acid (3NP), a mitochondrial toxin widely used as an in vitro model of Huntington’s disease (HD). Therefore, we now investigated 3NP and BDNF effects on astrocytes from two areas involved in HD: the striatum and the entire cortex, and their involvement in neuron survival. Methods We prepared primary cultured rat cortical or striatal astrocytes and treated them with BDNF and/or 3NP for 24 h. In these cells, we assessed expression of astrocyte markers, BDNF receptor, and glutamate transporters, and cytokine release. We prepared astrocyte-conditioned medium (ACM) from cortical and striatal astrocytes and tested its effect on a cellular model of HD. Results BDNF protected astrocytes from 3NP-induced death, increased expression of its own receptor, and activation of ERK in both cortical and striatal astrocytes. However, BDNF modulated glutamate transporter expression differently by increasing GLT1 and GLAST expression in cortical astrocytes but only GLT1 expression in striatal astrocytes. Striatal astrocytes released higher amounts of tumor necrosis factor-α than cortical astrocytes in response to 3NP but BDNF decreased this effect in both populations. 3NP decreased transforming growth factor-β release only in cortical astrocytes, whereas BDNF treatment increased its release only in striatal astrocytes. Finally, we evaluated ACM effect on a cellular model of HD: the rat striatal neuron cell line ST14A expressing mutant human huntingtin (Q120) or in ST14A cells expressing normal human huntingtin (Q15). Neither striatal nor cortical ACM modified the viability of Q15 cells. Only ACM from striatal astrocytes treated with BDNF and ACM from 3NP + BDNF-treated striatal astrocytes protected Q120 cells, whereas ACM from cortical astrocytes did not. Conclusions Data suggest that cortical and striatal astrocytes respond differently to mitochondrial toxin 3NP and BDNF. Moreover, striatal astrocytes secrete soluble neuroprotective factors in response to BDNF that selectively protect neurons expressing mutant huntingtin implicating that BDNF modulation of striatal astrocyte function has therapeutic potential against neurodegeneration. Graphical abstract

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FDA Recognizes Adalimumab's Joint Protective Effects in Psoriatic Arthritis

Rheumatology News ◽

10.1016/s1541-9800(06)71542-3 ◽

2006 ◽

Vol 5 (12) ◽

pp. 19

Author(s):

ELIZABETH MECHCATIE

Keyword(s):

Psoriatic Arthritis ◽

Protective Effects

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Melatonin reduces high levels of lipid peroxidation induced by potassium iodate in porcine thyroid

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000628 ◽

2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Paulina Iwan ◽

Jan Stepniak ◽

Malgorzata Karbownik-Lewinska

Keyword(s):

Lipid Peroxidation ◽

Oxidative Damage ◽

Membrane Lipids ◽

Chemical Properties ◽

Iodine Concentration ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Protective Effects ◽

Potassium Iodate ◽

Hormone Synthesis

Abstract. Iodine is essential for thyroid hormone synthesis. Under normal iodine supply, calculated physiological iodine concentration in the thyroid is approx. 9 mM. Either potassium iodide (KI) or potassium iodate (KIO3) are used in iodine prophylaxis. KI is confirmed as absolutely safe. KIO3 possesses chemical properties suggesting its potential toxicity. Melatonin (N-acetyl-5-methoxytryptamine) is an effective antioxidant and free radical scavenger. Study aims: to evaluate potential protective effects of melatonin against oxidative damage to membrane lipids (lipid peroxidation, LPO) induced by KI or KIO3 in porcine thyroid. Homogenates of twenty four (24) thyroids were incubated in presence of either KI or KIO3 without/with melatonin (5 mM). As melatonin was not effective against KI-induced LPO, in the next step only KIO3 was used. Homogenates were incubated in presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25 mM) without/with melatonin or 17ß-estradiol. Five experiments were performed with different concentrations of melatonin (5.0; 2.5; 1.25; 1.0; 0.625 mM) and one with 17ß-estradiol (1.0 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased LPO with the strongest damaging effect (MDA + 4-HDA level: ≈1.28 nmol/mg protein, p < 0.05) revealed at concentrations of around 15 mM, thus corresponding to physiological iodine concentrations in the thyroid. Melatonin reduced LPO (MDA + 4-HDA levels: from ≈0.97 to ≈0,76 and from ≈0,64 to ≈0,49 nmol/mg protein, p < 0.05) induced by KIO3 at concentrations of 10 mM or 7.5 mM. Conclusion: Melatonin can reduce very strong oxidative damage to membrane lipids caused by KIO3 used in doses resulting in physiological iodine concentrations in the thyroid.

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