Evidence map›Paper›PMID 34138412›Full record

ReviewCellular and molecular neurobiology2022

Progesterone and Allopregnanolone Neuroprotective Effects in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis.

Alejandro F De Nicola, María Meyer, Laura Garay, Maria Sol Kruse, Michael Schumacher, Rachida Guennoun, Maria Claudia Gonzalez Deniselle

Open access · greenAbstract readReview
In one paragraph

Review in Cellular and molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Alejandro F De NicolaLaboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina. alejandrodenicola@gmail.com.ORCID http://orcid.org/0000-0002-3523-9148
María MeyerLaboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina.
Laura GarayLaboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina.
Maria Sol KruseLaboratory of Neurobiology, Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina.
Michael SchumacherU1195 INSERM and University Paris Sud "Neuroprotective, Neuroregenerative and Remyelinating Small Molecules, 94276, Kremlin-Bicetre, France.ORCID http://orcid.org/0000-0001-6117-5371
Rachida GuennounU1195 INSERM and University Paris Sud "Neuroprotective, Neuroregenerative and Remyelinating Small Molecules, 94276, Kremlin-Bicetre, France.ORCID http://orcid.org/0000-0002-9219-7300
Maria Claudia Gonzalez DeniselleLaboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina.ORCID http://orcid.org/0000-0001-9121-0019
Consejo Nacional de Investigaciones Científicas y Técnicas · ARUniversité Paris-Sud · FR

Funding

Consejo Nacional de Investigaciones Científicas y Técnicas PIP 112 20120100016Ministry of Science and Technology PICT2012-0009Ministry of Science and Technology PICT 2019 3292Universidad de Buenos Aires 20020100100062Universidad de Buenos Aires 2002010010008
6 · The paper itself

Abstract

Progesterone regulates a number of processes in neurons and glial cells not directly involved in reproduction or sex behavior. Several neuroprotective effects are better observed under pathological conditions, as shown in the Wobbler mouse model of amyotrophic laterals sclerosis (ALS). Wobbler mice are characterized by forelimb atrophy due to motoneuron degeneration in the spinal cord, and include microgliosis and astrogliosis. Here we summarized current evidence on progesterone reversal of Wobbler neuropathology. We demonstrated that progesterone decreased motoneuron vacuolization with preservation of mitochondrial respiratory complex I activity, decreased mitochondrial expression and activity of nitric oxide synthase, increased Mn-dependent superoxide dismutase, stimulated brain-derived neurotrophic factor, increased the cholinergic phenotype of motoneurons, and enhanced survival with a concomitant decrease of death-related pathways. Progesterone also showed differential effects on glial cells, including increased oligodendrocyte density and downregulation of astrogliosis and microgliosis. These changes associate with reduced anti-inflammatory markers. The enhanced neurochemical parameters were accompanied by longer survival and increased muscle strength in tests of motor behavior. Because progesterone is locally metabolized to allopregnanolone (ALLO) in nervous tissues, we also studied neuroprotection by this derivative. Treatment of Wobbler mice with ALLO decreased oxidative stress and glial pathology, increased motoneuron viability and clinical outcome in a progesterone-like manner, suggesting that ALLO could mediate some progesterone effects in the spinal cord. In conclusion, the beneficial effects observed in different parameters support the versatile properties of progesterone and ALLO in a mouse model of motoneuron degeneration. The studies foresee future therapeutic opportunities with neuroactive steroids for deadly diseases like ALS.

Indexed as

Amyotrophic Lateral SclerosisNeuroprotective AgentsAnimalsDisease Models, AnimalMiceMotor NeuronsPregnanoloneProgesteroneSpinal CordNeuroprotective AgentsPregnanoloneProgesteroneAllopregnanoloneAmyotrophic lateral sclerosisNeurodegenerationNeuroprotectionProgesteroneWobbler mouse

Identifiers

PMID34138412
PMCPMC11441202
OpenAlexW3171687019

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.