Expression of aromatase and estrogen receptors in lumbar motoneurons of mice

Ji, Yingxiao; Zhao, Mei; Liu, Yaling; Chen, Li-sha; Hao, Pengli; Sun, Can Lan

doi:10.1016/j.neulet.2017.05.017

Cited by 13 publications

(17 citation statements)

References 51 publications

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“…We did not detect differences in circulating estradiol among groups in our study. However, it remains possible that estradiol concentrations within the CNS differ from that of the circulation, given that (a) various cell types throughout the CNS, including lumbar spinal motoneurons, express aromatase and have been shown to synthesize estradiol in culture (Ji et al, ; Rakotoarivelo et al, ), and (b) circulating estradiol concentrations do not necessarily reflect concentrations in peripheral tissues that express aromatase and other sex‐steroid hormone‐metabolizing enzymes (Yarrow et al, ; Yarrow, Wronski, & Borst, ).…”

Section: Discussionmentioning

confidence: 99%

“…We observed no differences in circulating estradiol among groups in our main study and no associations among estradiol and BBB scores. However, circulating testosterone was 35%–50% lower after SCI, suggesting potential differences in CNS estradiol concentrations, given that spinal motoneurons express aromatase and actively synthesize estradiol in culture (Ji et al, ; Rakotoarivelo et al, ). In support of this contention, testosterone treatment has been shown to attenuate the regression of dendritic length in spinal motoneurons after SCI (Byers et al, ), with androgenic and estrogenic actions each producing approximately 50% of the total effect (Sengelaub et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…given that (a) various cell types throughout the CNS, including lumbar spinal motoneurons, express aromatase and have been shown to synthesize estradiol in culture (Ji et al, 2017;Rakotoarivelo et al, 2004), and (b) circulating estradiol concentrations do not necessarily reflect concentrations in peripheral tissues that express aromatase and other sex-steroid hormone-metabolizing enzymes (Yarrow et al, 2010;Yarrow, Wronski, & Borst, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Yarrow

Kok

Phillips

et al. 2019

J of Neuroscience Research

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Loading and testosterone may influence musculoskeletal recovery after spinal cord injury (SCI). Our objectives were to determine (a) the acute effects of bodyweight‐supported treadmill training (TM) on hindlimb cancellous bone microstructure and muscle mass in adult rats after severe contusion SCI and (b) whether longer‐term TM with adjuvant testosterone enanthate (TE) delivers musculoskeletal benefit. In Study 1, TM (40 min/day, 5 days/week, beginning 1 week postsurgery) did not prevent SCI‐induced hindlimb cancellous bone loss after 3 weeks. In Study 2, TM did not attenuate SCI‐induced plantar flexor muscles atrophy nor improve locomotor recovery after 4 weeks. In our main study, SCI produced extensive distal femur and proximal tibia cancellous bone deficits, a deleterious slow‐to‐fast fiber‐type transition in soleus, lower muscle fiber cross‐sectional area (fCSA), impaired muscle force production, and levator ani/bulbocavernosus (LABC) muscle atrophy after 8 weeks. TE alone (7.0 mg/week) suppressed bone resorption, attenuated cancellous bone loss, constrained the soleus fiber‐type transition, and prevented LABC atrophy. In comparison, TE+TM concomitantly suppressed bone resorption and stimulated bone formation after SCI, produced near‐complete cancellous bone preservation, prevented the soleus fiber‐type transition, attenuated soleus fCSA atrophy, maintained soleus force production, and increased LABC mass. 75% of SCI+TE+TM animals recovered voluntary over‐ground hindlimb stepping, while no SCI and only 20% of SCI+TE animals regained stepping ability. Positive associations between testosterone and locomotor function suggest that TE influenced locomotor recovery. In conclusion, short‐term TM alone did not improve bone, muscle, or locomotor recovery in adult rats after severe SCI, while longer‐term TE+TM provided more comprehensive musculoskeletal benefit than TE alone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Yarrow

Kok

Phillips

et al. 2019

J of Neuroscience Research

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“…Estrogen sulfotransferase (EST, encoded by SULT1E1) catalyzes the sulfoconjugation and inactivation of estrogen. Reports showed that estrogen exerts neuroprotective and anti-inflammatory effects in ALS [ 63 , 64 ]. As EST mediates the metabolic deactivation of estrogen [ 65 ], drugs targeting EST may have potential regulation effects against ALS.…”

Section: Discussionmentioning

confidence: 99%

A Study to Decipher the Potential Effects of Butylphthalide against Central Nervous System Diseases Based on Network Pharmacology and Molecular Docking Integration Strategy

Zhao

Zheng

Feng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Butylphthalide (NBP), approved by the China National Medical Products Administration (NMPA) for the treatment of ischemic stroke (IS), showed pleiotropic potentials against central nervous system (CNS) diseases, including neuroprotection and cognitive deficits improvement. However, the effects and corresponding modes of action were not fully explored. This study was designed to investigate the potential of NBP against IS-associated CNS diseases based on network pharmacology (NP) and molecular docking (MD). Methods. IS was inputted as the index disease to retrieve the “associated diseases” in DisGeNET. Three-database-based IS genes were obtained and integrated (DisGeNET, Malacards, and OMIM). Then, IS-associated genes were identified by combining these genes. Meanwhile, PubMed references and online databases were applied to identify NBP target genes. The IS-related disease-disease association (DDA) network and NBP-disease regulation network were constructed and analyzed in Cytoscape. In silico MD and references were used to validate the binding affinity of NBP with critical targets and the potential of NBP against certain IS-related CNS disease regulation. Results. 175 NBP target genes were obtained, while 312 IS-related disease genes were identified. 36 NBP target genes were predicted to be associated with IS-related CNS diseases, including Alzheimer’s disease (AD), epilepsy, major depressive disorder (MDD), amyotrophic lateral sclerosis (ALS), and dementia. Six target genes (i.e., GRIN1, PTGIS, PTGES, ADRA1A, CDK5, and SULT1E1) indicating disease specificity index (DSI) >0.5 showed certain to good degree binding affinity with NBP, ranging from −9.2 to −6.7 kcal/mol. And the binding modes may be mainly related to hydrogen bonds and hydrophobic “bonds.” Further literature validations inferred that these critical NBP targets had a tight association with AD, epilepsy, ALS, and depression. Conclusions. Our study proposed a drug-target-disease integrated method to predict the drug repurposing potentials to associated diseases by application of NP and MD, which could be an attractive alternative to facilitate the development of CNS disease therapies. NBP may be promising and showed potentials to be repurposed for treatments for AD, epilepsy, ALS, and depression, and further investigations are warranted to be carefully designed and conducted.

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“…ERα and ERβ are also expressed in cytoplasmic and nuclear regions of spinal motoneurons [ 148 , 149 ] and cultured motoneurons actively synthesize E 2 in culture [ 149 ], owing to aromatase expression [ 148 , 149 ]. However, cultured rodent embryonic and adult spinal cord homogenates do not appear to synthesize E 2 when incubated with androstenedione [ 142 ] or T [ 141 ].…”

Section: Androgenic and Estrogenic Regulation Of Motoneuronsmentioning

confidence: 99%

Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury

Otzel

Lee

et al. 2018

IJMS

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Neuromuscular impairment and reduced musculoskeletal integrity are hallmarks of spinal cord injury (SCI) that hinder locomotor recovery. These impairments are precipitated by the neurological insult and resulting disuse, which has stimulated interest in activity-based physical rehabilitation therapies (ABTs) that promote neuromuscular plasticity after SCI. However, ABT efficacy declines as SCI severity increases. Additionally, many men with SCI exhibit low testosterone, which may exacerbate neuromusculoskeletal impairment. Incorporating testosterone adjuvant to ABTs may improve musculoskeletal recovery and neuroplasticity because androgens attenuate muscle loss and the slow-to-fast muscle fiber-type transition after SCI, in a manner independent from mechanical strain, and promote motoneuron survival. These neuromusculoskeletal benefits are promising, although testosterone alone produces only limited functional improvement in rodent SCI models. In this review, we discuss the (1) molecular deficits underlying muscle loss after SCI; (2) independent influences of testosterone and locomotor training on neuromuscular function and musculoskeletal integrity post-SCI; (3) hormonal and molecular mechanisms underlying the therapeutic efficacy of these strategies; and (4) evidence supporting a multimodal strategy involving ABT with adjuvant testosterone, as a potential means to promote more comprehensive neuromusculoskeletal recovery than either strategy alone.

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Expression of aromatase and estrogen receptors in lumbar motoneurons of mice

Cited by 13 publications

References 51 publications

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

A Study to Decipher the Potential Effects of Butylphthalide against Central Nervous System Diseases Based on Network Pharmacology and Molecular Docking Integration Strategy

Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury

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