Progesterone prevents depression-like behavior in a model of Parkinson's disease induced by 6-hydroxydopamine in male rats

Casas, Sebastián; García, Sebastián; Cabrera, Rodrigo; Nanfaro, Federico; Escudero, Consuelo; Yunes, Roberto

doi:10.1016/j.pbb.2011.06.012

Cited by 30 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…results]. Hence, consistent with the reported rescue results with PROG in 6-OHDA rats [19,20], we used higher doses of PROG in the present experiment. One hour after the first MPTP injection, the mice received 1 intraperitoneal injection of PROG [8 mg/kg (191 µg per injection) or 16 mg/kg (382 µg per injection)].…”

Section: Methodssupporting

confidence: 83%

“…A study in rats lesioned with 6-OHDA showed that the administration of chronic PROG (8 mg/kg) 24 h after injury increased the metabolism of striatal DA and exacerbated motor deficits induced by the lesion [19]. In contrast, others reported that the administration of high doses of PROG (4 mg/kg) 7 days after the striatal injection of 6-OHDA improved motor and cognitive deficits [20]. Although in the present study the therapeutic window of opportunity of PROG was not investigated, and PROG was administered relatively shortly after the lesion, the study on rats injured with 6-OHDA [20] suggests that the therapeutic window of opportunity of PROG is relatively wide, with benefits seen after a long period following the lesion.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, others reported that the administration of high doses of PROG (4 mg/kg) 7 days after the striatal injection of 6-OHDA improved motor and cognitive deficits [20]. Although in the present study the therapeutic window of opportunity of PROG was not investigated, and PROG was administered relatively shortly after the lesion, the study on rats injured with 6-OHDA [20] suggests that the therapeutic window of opportunity of PROG is relatively wide, with benefits seen after a long period following the lesion. These data suggest that PROG could be an interesting candidate for delaying the degeneration of DA neurons.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Neuroprotective Effect of Progesterone in MPTP-Treated Male Mice

et al. 2015

View full text Add to dashboard Cite

Background: Numerous studies have reported on the neuroprotective activity of estradiol, whereas the effect of the other ovarian steroid, progesterone, is much less documented. Methods: This study sought to investigate neuroprotection with a low dose of progesterone (1 µg) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated male mice to model Parkinson's disease and compare it to the effect of this steroid in intact mice (experiment 1). We also investigated if high doses of progesterone could protect dopaminergic neurons already exposed to MPTP (experiment 2). We measured progesterone effects on various dopaminergic markers [dopamine and its metabolites, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)] and on neuroactive steroids in both plasma and the brain. Results: For experiment 1, our results showed that progesterone completely prevented the effect of MPTP toxicity on dopamine concentrations, on the increase in the 3-methoxytyramine/dopamine ratio, as well as on VMAT2-specific binding in the striatum and the substantia nigra. Progesterone decreased MPTP effects on 3,4-dihydroxyphenylacetic acid concentrations and DAT-specific binding in the lateral part of the anterior striatum and in the middle striatum (medial and lateral parts). Progesterone treatment of intact mice had no effect on the markers investigated. For experiment 2, measures of dopaminergic markers in the striatum showed that 8 mg/kg of progesterone was the most effective dose to reduce MPTP effects, and more limited effects were observed with 16 mg/kg. We found that progesterone treatment increases the levels of brain progesterone itself as well as of its metabolites. Conclusion: Our result showed that progesterone has neuroprotective effects on dopaminergic neurons in MPTP-treated male mice.

show abstract

Section: Methodssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroprotective Effect of Progesterone in MPTP-Treated Male Mice

et al. 2015

View full text Add to dashboard Cite

show abstract

“… indicated that progesterone restores motoneurone morphology and the expression of α3 subunit Na,K‐ATPase mRNA, a neuronal enzyme controlling ion fluxes, neurotransmission, membrane potential and nutrient uptake, and also increased both muscle strength and survival time of Wobbler mice, a genetic model of spinal cord motor neurone disease. Progesterone prevents depression‐like behaviour in a model of Parkinson's disease induced by 6‐hydroxydopamine in male rats . Progesterone also exerts marked neuroprotective effects after spinal cord injury, cerebral ischaemia and stroke .…”

Section: Neurosteroids and Their Effects On Nervous System Functionsmentioning

confidence: 99%

Oestrogens and Progestagens: Synthesis and Action in the Brain

Rossetti

Cambiasso

Holschbach

et al. 2016

J Neuroendocrinology

111

View full text Add to dashboard Cite

When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side-chain cleavage, 3b-hydroxysteroid dehydrogenase/D5-D4 isomerase, cytochrome P450arom, steroid 5a-reductase and 3a-hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.

show abstract

“…129 One study showed that the administration of progesterone to a rat model of Parkinson's disease significantly reduced depression-like symptoms. 130 Administration of progesterone and allopregnanolone to rats suffering from severe cerebral ischaemia after middle cerebral artery occlusion was found to improve the structure and function of the hippocampus, although the preservation of cognitive functions is significantly better if progesterone was administered before inducing cerebral ischaemia. 131 It is hypothesised that, even though there is severe neuronal loss in the hippocampus after ischaemia, 132,133 the neuroprotective action of progesterone is able to enhance structure and plasticity of remaining neurons to condition them to carry out alternative strategies in the hippocampus or connected structures to restore some of the lost cognitive functions.…”

Section: Rodentsmentioning

confidence: 99%

Understanding the role of steroids in typical and atypical brain development: Advantages of using a “brain in a dish” approach

Adhya

Annuario

Lancaster

et al. 2018

J Neuroendocrinology

View full text Add to dashboard Cite

Steroids have an important role in growth, development, sexual differentiation and reproduction. All four classes of steroids, androgens, oestrogens, progestogens and glucocorticoids, have varying effects on the brain. Androgens and oestrogens are involved in the sexual differentiation of the brain, and also influence cognition.Progestogens such as progesterone and its metabolites have been shown to be involved in neuroprotection, although their protective effects are timing-dependent.Glucocorticoids are linked with stress and memory performance, also in a dose-and time-dependent manner. Importantly, dysfunction in steroid function has been implicated in the pathogenesis of disease. Moreover, regulating steroid-signalling has been suggested as potential therapeutic avenue for the treatment of a number of neurodevelopmental, psychiatric and neurodegenerative disorders. Therefore, clarifying the role of steroids in typical and atypical brain function is essential for understanding typical brain functions, as well as determining their potential use for pharmacological intervention in the atypical brain. However, the majority of studies have thus far have been conducted using animal models, with limited work using native human tissue or cells. Here, we review the effect of steroids in the typical and atypical brain, focusing on the cellular, molecular functions of these molecules determined from animal models, and the therapeutic potential as highlighted by human studies. We further discuss the promise of human-induced pluripotent stem cells, including advantages of using three-dimensional neuronal cultures (organoids) in high-throughput screens, in accelerating our understanding of the role of steroids in the typical brain, and also with respect to their therapeutic value in the understanding and treatment of the atypical brain. K E Y W O R D S17β-oestradiol, androgens, autism spectrum conditions, neurodegenerative disease, neurodevelopmental disorders, oestrogens, psychiatric, schizophrenia, stem cells, synapse, testosterone This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

Progesterone prevents depression-like behavior in a model of Parkinson's disease induced by 6-hydroxydopamine in male rats

Cited by 30 publications

References 38 publications

Neuroprotective Effect of Progesterone in MPTP-Treated Male Mice

Neuroprotective Effect of Progesterone in MPTP-Treated Male Mice

Oestrogens and Progestagens: Synthesis and Action in the Brain

Understanding the role of steroids in typical and atypical brain development: Advantages of using a “brain in a dish” approach

Contact Info

Product

Resources

About