Publication date: November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 174
Author(s): Maria Meyer, Laura I. Garay, María Sol Kruse, Agustina Lara, Gisella Gargiulo-Monachelli, Michael Schumacher, Rachida Guennoun, Hector Coirini, Alejandro F. De Nicola, Maria Claudia Gonzalez Deniselle
Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by progressive death of motoneurons. The Wobbler (WR) mouse is a preclinical model sharing neuropathological similarities with human ALS. We have shown that progesterone (PROG) prevents the progression of motoneuron degeneration. We now studied if allopregnanolone (ALLO), a reduced metabolite of PROG endowed with gabaergic activity, also prevents WR neuropathology. Sixty-day old WRs remained untreated or received two steroid treatment regimens in order to evaluate the response of several parameters during early or prolonged steroid administration. ALLO was administered s.c. daily for 5days (4mg/kg) or every other day for 32days (3, 3mg/kg), while another group of WRs received a 20mg PROG pellet s.c. for 18 or 60days. ALLO administration to WRs increased ALLO serum levels without changing PROG and 5 alpha dihydroprogesterone (5α-DHP), whereas PROG treatment increased PROG, 5α-DHP and ALLO. Untreated WRs showed higher basal levels of serum 5α-DHP than controls. In the cervical spinal cord we studied markers of oxidative stress or associated to trophic responses. These included nitric oxide synthase (NOS) activity, motoneuron vacuolation, MnSOD immunoreactivity (IR), brain derived neurotrophic factor (BDNF) and TrkB mRNAs, p75 neurotrophin receptor (p75NTR) and, cell survival or death signals such as pAKT and the stress activated kinase JNK. Untreated WRs showed a reduction of MnSOD-IR and BDNF/TrkB mRNAs, associated to high p75NTR in motoneurons, neuronal and glial NOS hyperactivity and neuronal vacuolation. Also, low pAKT, mainly in young WRs, and a high pJNK in the old stage characterized WŔs spinal cord. Except for MnSOD and BDNF, these alterations were prevented by an acute ALLO treatment, while short-term PROG elevated MnSOD. Moreover, after chronic administration both steroids enhanced MnSOD-IR and BDNF mRNA, while attenuated pJNK and NOS in glial cells. Long-term PROG also increased pAKT and reduced neuronal NOS, parameters not modulated by chronic ALLO. Clinically, both steroids improved muscle performance. Thus, ALLO was able to reduce neuropathology in this model. Since high oxidative stress activates p75NTR and pJNK in neurodegeneration, steroid reduction of these molecules may provide adequate neuroprotection. These data yield the first evidence that ALLO, a gabaergic neuroactive steroid, brings neuroprotection in a model of motoneuron degeneration.
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Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Δευτέρα 6 Νοεμβρίου 2017
Protective effects of the neurosteroid allopregnanolone in a mouse model of spontaneous motoneuron degeneration
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- Developmental refinement of synaptic transmission ...
- Photoluminescent properties of single crystal diam...
- Does the reduction of inferior turbinate size affe...
- Pharmacotherapy for social anxiety disorder: Inter...
- A case of segmental stiff skin syndrome treated wi...
- CONTENTS 1
- CONTENTS 2
- Intralabyrinthine sporadic endolymphatic sac tumour
- Direct Observation vs. Video-Based Assessment in F...
- Characterization of Vessel Deformations During EVA...
- Analysis of Academic Medical Center Graduate Medic...
- 360° Operative Videos: A Randomised Cross-Over Stu...
- Textual Analysis of General Surgery Residency Pers...
- Central leptin regulates heart lipid content by se...
- Vitamin D, the placenta and early pregnancy: effec...
- Visible-light-driven photocatalytic inactivation o...
- Encapsulation of fluorescein into nanozeolites L a...
- Utilization of red mud and Pb/Zn smelter waste for...
- A novel method of utilization of hot dip galvanizi...
- A detailed study on Sn4+ doped ZnO for enhanced ph...
- Zn nanoparticle formation in FIB irradiated single...
- Effects of the carrier concentration on polarity d...
- Evaluating the diffusive gradients in thin films t...
- Soil geochemical factors regulate Cd accumulation ...
- Study of the iron nitride FeN into the megabar regime
- Public health approach to minimize the prevalence ...
- Necessity to strengthen prevention activities and ...
- The effect of space face games on the amount of ch...
- Delivering comprehensive sexuality education among...
- Mobilizing youth population to spread peace in the...
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- Building an effective mechanism to respond to the ...
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- Percutaneous CT-guided facet joint synovial cyst r...
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- Value of elective radiation oncology rotations: ho...
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- An Asymptomatic Man With an Abnormal ECG.
- Impact of Heart Outcomes Prevention Evaluation Tri...
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- Response by Mehra et al to Letter Regarding Articl...
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- Correction to: Role of Biomarkers for the Preventi...
- Correction to: American Heart Association's Call t...
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- Heme and hemolysis in innate immunity: adding insu...
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- Single-Neuron Correlates of Awareness during Atten...
- Parallel Distributed Processing Theory in the Age ...
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