Androgen regulates trkB immunolabeling in spinal motoneurons

Osborne, Mark C.; Verhovshek, Tom; Sengelaub, Dale R.

doi:10.1002/jnr.21122

Cited by 48 publications

(51 citation statements)

References 41 publications

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“…Unexpectedly, we find no effect of androgens on the expression of BDNF mRNA in muscles of either male or female Wt mice, contrary to previously published results in rats (Osborne et al, 2007; Ottem et al, 2007; Verhovshek et al, 2010). Nonetheless, the pattern of results in myogenic and 97Q Tg mice underscores the fact that only the combination of T and the disease allele leads to impairments in both BDNF mRNA expression and motor function in these SBMA models.…”

Section: Discussioncontrasting

confidence: 99%

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA

Halievski

Henley

Domino

et al. 2015

Experimental Neurology

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Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived neurotrophic factor (BDNF) mediates effects of androgens on neuromuscular systems, we asked whether BDNF expression is impaired in two different transgenic (Tg) mouse models of SBMA, the so called “97Q” and “myogenic” SBMA models. The 97Q model globally overexpresses a full length human AR with 97 glutamine repeats whereas the myogenic model of SBMA overexpresses a wild-type rat androgen receptor (AR) only in skeletal muscle fibers. Using quantitative PCR, we find that muscle BDNF mRNA declines in an androgen-dependent manner in both models, paralleling changes in motor function, with robust deficits (6-8 fold) in both fast and slow twitch muscle of impaired Tg males. Castration rescues or reverses disease-related deficits in muscle BDNF mRNA in both models, paralleling its effect on motor function. Moreover, when disease is acutely induced in Tg females, both motor function and muscle BDNF mRNA expression plummet, with the deficit in muscle BDNF emerging before overt motor dysfunction. That androgen-dependent motor dysfunction is tightly associated with a robust and early down-regulation of muscle BDNF mRNA suggests that BDNF delivered to muscle may have therapeutic value for SBMA.

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Section: Discussioncontrasting

confidence: 99%

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA

Halievski

Henley

Domino

et al. 2015

Experimental Neurology

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“…To more carefully assess potential differences in the distribution of staining intensities, immunostaining of interpositus neurons was then categorized as being either light (having a relative intensity of at least one and a half standard deviations below the mean of controls), moderately light (between one and one and a half standard deviations below the mean), average (within one standard deviation of the mean), moderately dark (between one and one and a half standard deviations above the mean), or dark (greater than one and a half standard deviations above the mean). This method has been shown to be reliable for categorizing neurons by immunostaining intensity for subsequent frequency analyses and is sensitive to differences in protein expression assessed immunohistochemically (Osborne et al, 2007).…”

Section: Gr Immunohistochemistry and Quantification Of Gr Expressionmentioning

confidence: 99%

Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum

Wilber

Southwood

Sokoloff

et al. 2007

Developmental Neurobiology

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Neonatal maternal separation alters learning and memory. Glucocorticoids also modulate adult learning and memory, and neonatal maternal separation alters forebrain glucocorticoid receptor (GR) concentrations. We used eyeblink classical conditioning to assess the effect of neonatal maternal separation on associative learning. We assessed delay eyeblink conditioning, GR expression, and total neuron number in the interpositus nucleus, a critical site of plasticity in eyeblink conditioning, in adult rats that had undergone either standard animal facilities rearing, handling for 15 min, or maternal separation for either 15 or 60 min per day on postnatal days 2-14. At 2-3 months of age, delay eyeblink classical conditioning was assessed. Brains were processed for GR immunohistochemistry, and GR expression in the interpositus nucleus was assessed using a computer-based densitometry system. Neuron counts and nuclear volumes were obtained from an alternate series of thionin-stained sections. Maternal separation significantly impaired eyeblink conditioning in male but not female rats. Handling and maternal separation did not significantly affect interpositus neuron number and volume. However, prolonged maternal separation significantly increased GR expression in the posterior interpositus in males, and increases were correlated with eyeblink conditioning. In female rats, maternal separation and handling did not significantly alter interpositus neuron number, volume, or GR protein expression, and GR expression did not correlate with eyeblink conditioning. Thus, neonatal maternal separation produces adult deficits in eyeblink conditioning and alterations in GR expression in its neural substrate in a sex-dependent manner.

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“…(Drakos et al ., 2007)7 This has been made easier by the monoclonal technology. The most important diagnostic applications of IHC are related to detection of various antigens which include actin, alkaline phosphatase, alpha-actin, alpha-1 antrichymotrypsin, alpha-1 antitrypsin, alpha-fetoprotein, alpha lactalbumin, angiotensin converting enzyme, basement membrane, blood group antigens, bone gamma-carboxyglutamic acid (GLA) protein, CA19.9, CA 125, cadherins, calmodulin, cancer-associated carbohydrates, (Osborne et al ., 2007)11 carbonic anhydrase C, carcinoembryogenic antigen (CEA) and casein. Others include cluster of differentiation 31 (CD31), cluster of differentiation 34 (CD34), chromogranin, collagen, creatine kinase, cytokeratins, desmin, endorphins, enolase, enzymes, factor XIIIa, factor-VIII-related antigen, ferritin, fibrin, haemoglobin, histaminase, human leukocyte antigen (HLAs), hormone receptors, human chorionic gonadotropin (hCG), human placental lactogens, p53, Phosphatase and tensin homolog (PTEN), and immunoglobulins.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…Another application could be illustrated by the study of Osborne et al ., (2007),11 in which they used immunohistochemical methods to examine the frequency of cells immunolabelled for Tyrosine receptor kinase B (trkB) receptors in two populations of spinal motor neurons, the hormone-sensitive sexually dimorphic motor neurons of the spinal nucleus of the bulbocavernosus (SNB) and the non-dimorphic motor neurons innervating the muscles of the quadriceps femoris. In both, the highly androgen-sensitive SNB motor neurons innervating the quadriceps femoris muscles, the frequency of motor neurons intensely immunolabelled for trkB receptors was regulated by the presence of testosterone.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Biomedical techniques in translational studies: The journey so far

Abdulkareem

2014

Niger Med J

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Biomedical techniques have wide clinical application in many fields of medicine such as oncology, rheumatology, immunology, genomics, cardiology and diagnostics; among others. This has been made possible with the use of genetic engineering and a number of techniques like Immunohistochemistry (IHC), Fluorescent Microscopy, Cell Culture, Genetically Modified (GM) Cells, Monoclonal Antibodies (MAbs), Polymerase Chain Reaction (PCR) and Western blotting. The aim of this literature review is to explore the foundations and bases of the commonly used biomedical techniques, as well as their applications in biomedical research and clinical medicine in general. This review also aims to shed some light on more recent advances in genetic engineering, especially in relation to genetically modified cells and use of monoclonal antibodies which have found more increasing use and relevance in genomics, oncology, rheumatology, immunology, cardiology as well as diagnostics, and have revolutionised patient care, while at the same time resulting in improved standard of health care. Unfortunately, some of these new techniques are associated with unwanted side effects which may pose a risk to the people they are actually intended for. Therefore, there is need for strict regulations and guidelines to control the use and implementation of some of these novel techniques.

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Androgen regulates trkB immunolabeling in spinal motoneurons

Cited by 48 publications

References 41 publications

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA

Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum

Biomedical techniques in translational studies: The journey so far

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