Differential effects of dihydrotestosterone and estrogen on the development of motoneuron morphology in a sexually dimorphic rat spinal nucleus

Goldstein, L. A.; Sengelaub, Dale R.

doi:10.1002/neu.480250711

Cited by 70 publications

(113 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data are expressed as a percentage of dendritic length in intact males. (Compiled from data originally published in , Goldstein and Sengelaub, 1994, Burke et al, 1997 Testosterone treatment is neurotherapeutic in SNB motoneurons, attenuating induced dendritic atrophy resulting from the death of nearby motoneurons. (Left) Darkfield digital micrographs of transverse sections through the lumbar spinal cords of males whose SNB motoneurons have been partially depleted with the toxin saporin, and then left untreated (SAP) or given supplemental testosterone (SAP + T), after BHRP injection into the left BC muscle.…”

Section: Discussionmentioning

confidence: 99%

“…SNB dendrites in castrates that receive testosterone replacement grow normally, attaining the typical exuberant length by P28 . Interestingly, treatment of castrated males with either of testosterone's metabolites, DHT or estradiol, supports SNB dendritic growth through the first 4 postnatal weeks (Goldstein and Sengelaub, 1994), but typically not to the level of testosterone-treated or intact males. Similarly, blocking estrogen receptors by systemic treatment with tamoxifen (Taylor et al, 1995), or preventing estradiol synthesis with fadrozole (Burke et al, 1999), during the period of dendritic growth in gonadally intact males results in dendritic lengths that are significantly below those of normal males (and comparable to those of DHT-treated castrates).…”

Section: Dendritic Developmentmentioning

confidence: 99%

“…Local blockade of estrogen receptors at the BC muscle of gonadally intact males results in severely reduced dendritic lengths similar to those seen in castrates, whereas local administration of estradiol to the BC muscle of castrated males supports dendritic growth. This estrogenic influence is limited to the early postnatal period: the morphology of SNB motoneurons is insensitive to estrogens after 4 weeks of age (Goldstein and Sengelaub, 1994;Hebbeler et al, 2001;Warren and Sengelaub, 2002) or in adulthood (Forger et al, 1992;Fargo and Sengelaub, 2007). The transient influence of estrogens on SNB dendritic growth is coincident with a period in which high levels of NMDA receptors are expressed in the spinal cord, and locally in the SNB nucleus (Verhovshek et al, 2005).…”

Section: Dendritic Developmentmentioning

confidence: 99%

See 2 more Smart Citations

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

Sengelaub

Forger

2008

Hormones and Behavior

View full text Add to dashboard Cite

Cell number in the spinal nucleus of the bulbocavernosus (SNB) of rats was the first neural sex difference shown to differentiate under the control of androgens, acting via classical intracellular androgen receptors. SNB motoneurons reside in the lumbar spinal cord and innervate striated muscles involved in copulation, including the bulbocavernosus (BC) and levator ani (LA). SNB cells are much larger and more numerous in males than in females, and the BC/LA target muscles are reduced or absent in females. The relative simplicity of this neuromuscular system has allowed for considerable progress in pinpointing sites of hormone action, and identifying the cellular bases for androgenic effects. It is now clear that androgens act at virtually every level of the SNB system, in development and throughout adult life. In this review we focus on effects of androgens on developmental cell death of SNB motoneurons and BC/LA muscles; the establishment and maintenance of SNB motoneuron soma size and dendritic length; BC/LA muscle morphology and physiology; and behaviors controlled by the SNB system. We also describe new data on neurotherapeutic effects of androgens on SNB motoneurons after injury in adulthood.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Dendritic Developmentmentioning

confidence: 99%

Section: Dendritic Developmentmentioning

confidence: 99%

See 1 more Smart Citation

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

Sengelaub

Forger

2008

Hormones and Behavior

View full text Add to dashboard Cite

show abstract

“…Each injection consisted of 300 μg estradiol benzoate (1,3,5(10)-estratrien-3, 17β-diol 3-benzoate; Steraloids) dissolved in 0.15 mL of sesame oil. This dose and route was chosen because we have previously used it to successfully maintain normal levels of electrophysiological activity in SNB motoneurons in castrated males (Fargo et al, 2003; see also Holmes and Sachs, 1992), and is effective in supporting SNB dendritic morphology during development (Goldstein and Sengelaub, 1994;Burke et al, 1997;Hebbeler and Sengelaub, 2003). Daily estradiol injections continued until sacrifice.…”

Section: Animalsmentioning

confidence: 99%

Androgenic, but not estrogenic, protection of motoneurons from somal and dendritic atrophy induced by the death of neighboring motoneurons

Fargo

Sengelaub

2007

Developmental Neurobiology

View full text Add to dashboard Cite

Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have been investigating the effects of motoneuron loss on surviving motoneurons in a lumbar motor nucleus, the spinal nucleus of the bulbocavernosus (SNB). SNB motoneurons undergo marked dendritic and somal atrophy following the experimentally induced death of other nearby SNB motoneurons. However, treatment with testosterone at the time of lesioning attenuates this atrophy. Because testosterone can be metabolized into the estrogen estradiol (as well as other physiologically active steroid hormones), it was unknown whether the protective effect of testosterone was an androgen effect, an estrogen effect, or both. In the present experiment, we used a retrogradely transported neurotoxin to kill the majority of SNB motoneurons on one side of the spinal cord only in adult male rats. Some animals were also treated with either testosterone, the androgen dihydrotestosterone (which cannot be converted into estradiol), or the estrogen estradiol. As seen previously, partial motoneuron loss led to reductions in soma area and in dendritic length and extent in surviving motoneurons. Testosterone and dihydrotestosterone attenuated these reductions, but estradiol had no protective effect. These results indicate that the neuroprotective effect of testosterone on the morphology of SNB motoneurons following partial motoneuron depletion is an androgen effect rather than an estrogen effect.

show abstract

“…normal development 24,33,34 , after changes in dendritic interactions 33 and afferent input [35][36][37] , and after injury 6,[21][22][23]38 .…”

Section: Dendritic Lengthmentioning

confidence: 99%

Inhibition of Cytosolic Phospholipase A₂Has Neuroprotective Effects on Motoneuron and Muscle Atrophy after Spinal Cord Injury

Liu

Byers

Lam

et al. 2021

Journal of Neurotrauma

View full text Add to dashboard Cite

Surviving motoneurons undergo dendritic atrophy after spinal cord injury (SCI), suggesting an important therapeutic target for neuroprotective strategies to improve recovery of function after SCI. Our previous studies showed that phospholipase A 2 (PLA 2 ) may play an important role in the pathogenesis of SCI. In the present study, we investigated whether blocking cPLA 2 pharmacologically with arachidonyl trifluoromethyl ketone (ATK) or genetically using cPLA 2 knockout (KO) mice attenuates motoneuron atrophy following SCI. C57BL/6 mice received either sham or contusive SCI at the T10 level. At 30 min after SCI, mice were treated with ATK or vehicle. Four weeks later, motoneurons innervating the vastus lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing were also assessed, as were muscle weight, fiber cross-sectional area, and motor endplate size and density. ATK administration reduced percent lesion volume and increased percent volume of spared white matter compared to the vehicle-treated control animals. SCI with or without ATK treatment had no effect on the number or soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in dendritic length of quadriceps motoneurons in untreated animals, and this decrease was completely prevented by treatment with ATK. Similarly, the vastus lateralis muscle weights of untreated SCI animals were smaller than those of sham-surgery controls, and these reductions were prevented by ATK treatment. No effects on fiber cross-sectional areas, motor endplate area or density were observed across treatment groups. Remarkably, genetically deleting cPLA 2 in cPLA 2 KO mice attenuated dendritic atrophy after SCI. These findings suggest that after SCI, cord tissue damage and regressive changes in motoneuron and muscle morphology can be reduced by inhibition of cPLA 2 , further supporting a role for cPLA 2 as a neurotherapeutic target for SCI treatment.

show abstract

Differential effects of dihydrotestosterone and estrogen on the development of motoneuron morphology in a sexually dimorphic rat spinal nucleus

Cited by 70 publications

References 77 publications

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

Androgenic, but not estrogenic, protection of motoneurons from somal and dendritic atrophy induced by the death of neighboring motoneurons

Inhibition of Cytosolic Phospholipase A₂Has Neuroprotective Effects on Motoneuron and Muscle Atrophy after Spinal Cord Injury

Contact Info

Product

Resources

About

Differential effects of dihydrotestosterone and estrogen on the development of motoneuron morphology in a sexually dimorphic rat spinal nucleus

Cited by 70 publications

References 77 publications

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

Androgenic, but not estrogenic, protection of motoneurons from somal and dendritic atrophy induced by the death of neighboring motoneurons

Inhibition of Cytosolic Phospholipase A2Has Neuroprotective Effects on Motoneuron and Muscle Atrophy after Spinal Cord Injury

Contact Info

Product

Resources

About

Inhibition of Cytosolic Phospholipase A₂Has Neuroprotective Effects on Motoneuron and Muscle Atrophy after Spinal Cord Injury