Biomedical subjects

Yasushi Kobayashi

Publications and source records attributed to Yasushi Kobayashi.

At least 19 recordsLinked to original sources

PubMed2006

Molecular basis of late-flowering phenotype caused by dominant epi-alleles of the FWA locus in Arabidopsis.

The late-flowering phenotype of dominant fwa mutants is caused by hypomethylation in the FWA locus leading to ectopic expression of a homeodomain leucine zipper (HD-ZIP) protein. However, little is known about whether FWA has any role in regulation of flowering and how ectopically expressed FWA delays flowering. Through analysis of FWA expression in wild-type seedlings, it was shown that FWA is not expressed during the vegetative phase. This suggests that FWA has no role in flowering. The previous reports that fwa suppressed the precocious-flowering phenotype of plants overexpressing FLOWERING LOCUS T (FT) suggest that the flowering pathway(s) either at and/or downstream of FT is blocked by FWA. Comparison of gene expression profiles in three genetic backgrounds ectopically expressing FWA and their respective wild types failed to detect common changes, ruling out the possibility that FWA acts through transcriptional misregulation. Yeast two-hybrid analysis and in vitro pull-down assay showed that FWA protein can specifically interact with FT protein. The importance of protein interaction with FT in delaying flowering was supported by studies involving N-terminal and C-terminal truncations of FWA. The C-terminal truncation with abolished interaction did not delay flowering when overexpressed, while the N-terminal truncation, which retains interaction, did. Specific interaction of FWA with FT enabled us to use FWA protein as a specific inhibitor of FT protein function. Through tissue-specific ectopic expression of FWA, further support for the shoot apex being the site of action of FT protein was provided.

Alleles↗

PubMed2006

Direct determination of single nucleotide polymorphism haplotype of NFKBIL1 promoter polymorphism by DNA conformation analysis and its application to association study of chronic inflammatory diseases.

We previously revealed that one of the human leukocyte antigen-linked susceptibility genes for Takayasu's arteritis (TA) was mapped between TNFA and MICB loci and that -63T allele of NFKBIL1, which is between TNFA and MICB loci, was associated with rheumatoid arthritis (RA) in the Japanese population. We have developed a novel typing method based on reference strand-mediated conformation analysis for the upstream sequence of the NFKBIL1 gene, where -422 (T)8/(T)9, -325 C/G, -263 A/G, and -63 T/A polymorphisms were found. Upon the analysis of the patients with TA (n = 84), those with RA (n = 120), and healthy control subjects (n = 217), five common haplotypes named IKBLp*01 through IKBLp*05 were found in the Japanese population. The frequency of IKBLp*03 was significantly increased in the patient with TA (57.1% vs 35.0%, giving an odds ratio of 2.47). In addition, the frequency of IKBLp*01, but not that of other -63T-bearing alleles, was increased in the patients with RA (73.3% vs 58.1%, giving an odds ratio of 1.99), suggesting that the susceptibility to RA was conferred not by -63T alone but by combination of single nucleotide polymorphisms in the NFKBIL1 promoter. A higher promoter activity associated with IKBLp*03 and a lower activity associated with IKBLp*01 may contribute to the susceptibility to TA and RA, respectively.

Adaptor Proteins, Signal Transducing↗

PubMed2005

FD, a bZIP protein mediating signals from the floral pathway integrator FT at the shoot apex.

FLOWERING LOCUS T (FT) is a conserved promoter of flowering that acts downstream of various regulatory pathways, including one that mediates photoperiodic induction through CONSTANS (CO), and is expressed in the vasculature of cotyledons and leaves. A bZIP transcription factor, FD, preferentially expressed in the shoot apex is required for FT to promote flowering. FD and FT are interdependent partners through protein interaction and act at the shoot apex to promote floral transition and to initiate floral development through transcriptional activation of a floral meristem identity gene, APETALA1 (AP1). FT may represent a long-distance signal in flowering.

Arabidopsis↗

PubMed2005

TWIN SISTER OF FT (TSF) acts as a floral pathway integrator redundantly with FT.

In Arabidopsis, several genetic pathways controlling the floral transition (flowering) are integrated at the transcriptional regulation of FT, LFY and SOC1. TSF is the closest homolog of FT in Arabidopsis. TSF expression was induced rapidly upon activation of CONSTANS (CO). The mRNA levels of TSF and FT showed similar patterns of diurnal oscillation and response to photoperiods: an evening peak, higher levels in long day (LD) than in short day (SD) conditions, and immediate up-regulation upon day-length extension. These observations suggest that TSF is a direct regulatory target of CO. tsf mutation delayed flowering in SD conditions and enhanced the phenotype of ft in both LD and SD conditions. TSF and FT also shared similar modes of regulation by FLC, an integrator of autonomous and vernalization pathways, and other factors such as EBS and PHYB. Consistently, TSF overexpression caused a precocious flowering phenotype independent of photoperiods or CO, or FLC. These observations suggest that TSF is a new member of the floral pathway integrators and promotes flowering largely redundantly with FT but makes a distinct contribution in SD conditions. TSF and FT seem to act independently of each other and of LFY, and partially upstream of SOC1. Interestingly, the expression patterns of TSF and FT in seedlings did not overlap, although both were expressed in the phloem tissues. Our work revealed additional complexity and spatial aspects of the regulatory network at the pathway integration level. We propose that the phloem is the site where multiple regulatory pathways are integrated at the transcriptional regulation of FT and TSF.

Arabidopsis↗

PubMed2005

Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients.

Spinal and bulbar muscular atrophy (SBMA) is an inherited adult onset motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR), affecting only males. The characteristic pathological finding is nuclear inclusions (NIs) consisting of mutant AR with an expanded polyQ in residual motor neurons, and in certain visceral organs. We immunohistochemically examined 11 SBMA patients at autopsy with 1C2, an antibody that specifically recognizes expanded polyQ. Our study demonstrated that diffuse nuclear accumulation of mutant AR was far more frequent and extensive than NIs being distributed in a wide array of CNS nuclei, and in more visceral organs than thus far believed. Mutant AR accumulation was also present in the cytoplasm, particularly in the Golgi apparatus; nuclear or cytoplasmic predominance of accumulation was tissue specific. Furthermore, the extent of diffuse nuclear accumulation of mutant AR in motor and sensory neurons of the spinal cord was closely related to CAG repeat length. Thus, diffuse nuclear accumulation of mutant AR apparently is a cardinal pathogenetic process underlying neurological manifestations, as in SBMA transgenic mice, while cytoplasmic accumulation may also contribute to SBMA pathophysiology.

Aged↗

PubMed2005

Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis.

The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons isolated from autopsied patients with sporadic ALS were examined. Gene expression was quantitatively assessed by real-time reverse transcription polymerase chain reaction and in situ hybridization. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were downregulated, and 1% were upregulated in motor neurons. Downregulated genes included those associated with cytoskeleton/axonal transport, transcription, and cell surface antigens/receptors, such as dynactin, microtubule-associated proteins, and early growth response 3 (EGR3). In contrast, cell death-associated genes were mostly upregulated. Promoters for cell death pathway, death receptor 5, cyclins A1 and C, and caspases-1, -3, and -9, were upregulated, whereas cell death inhibitors, acetyl-CoA transporter, and NF-kappaB were also upregulated. Moreover, neuroprotective neurotrophic factors such as ciliary neurotrophic factor (CNTF), Hepatocyte growth factor (HGF), and glial cell line-derived neurotrophic factor were upregulated. Inflammation-related genes, such as those belonging to the cytokine family, were not, however, significantly upregulated in either motor neurons or ventral horns. The motor neuron-specific gene expression profile in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death and are helpful for developing new therapeutic strategies.

Adult↗

PubMed2005

Ectopic expression of an FT homolog from citrus confers an early flowering phenotype on trifoliate orange (Poncirus trifoliata L. Raf.).

Citrus FT (CiFT) cDNA, which promoted the transition from the vegetative to the reproductive phase in Arabidopsis thaliana, when constitutively expressed was introduced into trifoliate orange (Poncirus trifoliata L. Raf.). The transgenic plants in which CiFT was expressed constitutively showed early flowering, fruiting, and characteristic morphological changes. They started to flower as early as 12 weeks after transfer to a greenhouse, whereas wild-type plants usually have a long juvenile period of several years. Most of the transgenic flowers developed on leafy inflorescences, apparently in place of thorns; however, wild-type adult trifoliate orange usually develops solitary flowers in the axils of leaves. All of the transgenic lines accumulated CiFT mRNA in their shoots, but there were variations in the accumulation level. The transgenic lines showed variation in phenotypes, such as time to first flowering and tree shape. In F(1) progeny obtained by crossing 'Kiyomi' tangor (C. unshiu x sinensis) with the pollen of one transgenic line, extremely early flowering immediately after germination was observed. The transgene segregated in F(1) progeny in a Mendelian fashion, with complete co-segregation of the transgene and the early flowering phenotype. These results showed that constitutive expression of CiFT can reduce the generation time in trifoliate orange.

Agrobacterium tumefaciens↗

PubMed2005

[Stereotactic vacuum-assisted breast biopsy (Mammotome biopsy) for non-palpable microcalcification on mammography].

PURPOSE: The purpose of this study was to assess the benefits of stereotactic vacuum-assisted breast biopsy in patients with non-palpable microcalcification detected on mammography. METHODS: Between October 2001 and November 2003, stereotactic Mammotome biopsies were performed for 150 microcalcified lesions on mammography using the prone-type stereotactic vacuum-assisted breast biopsy system (Mammotest and Mammovision, Fischer, Denver, USA) . The mammography findings were classified according to the guidelines of The Japan Radiological Society/The Japan Association of Radiological Technologists. Ninety-eight cases were category 3, 38 were category 4, and 14 were category 5. RESULTS: All cases were determined to be cases of microcalcification by specimen radiography or histology. Complications were negligible. One hundred twenty of the cases were mastopathy, and 30 of them were breast cancer (14 were ductal carcinoma in situ, 7 were ductal carcinoma in situ with microinvasion, and 9 were invasive ductal carcinoma). Twenty-seven breast cancers were diagnosed as category 4 or 5 (51.9%) on mammography. The operative stages of 27 cases were as follows: 7 were stage 0, 17 were stage 1, and 3 were stage 2A. Twenty-four of 27 (88.9%) were early breast cancers. CONCLUSION: Mammotome biopsy is a safe and useful modality for the histological diagnosis of non-palpable microcalcifications.

Adult↗

PubMed2005

Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT.

UNLABELLED: The purpose of this study was to evaluate the ability of (18)F-FDG PET to identify aortitis and to localize and follow disease activity in patients with Takayasu arteritis. The value of using (18)F-FDG PET coregistered with enhanced CT in determining vascular lesion sites and inflammatory activity was assessed. METHODS: Takayasu arteritis was diagnosed according to the predefined criteria. Eleven patients with Takayasu arteritis in the active stage, 3 patients with Takayasu arteritis in the inactive stage, and 6 healthy subjects underwent (18)F-FDG PET coregistered with enhanced CT and the inflammatory vascular lesion was evaluated by using the standardized uptake value (SUV) of (18)F-FDG accumulation as an index. Two patients with active disease were analyzed by sequential (18)F-FDG PET scans during treatment. RESULTS: The (18)F-FDG PET revealed intense (18)F-FDG accumulation (SUV > or = 2.7) in the vasculature of 2 of the 11 cases in the active stage of Takayasu arteritis. The other 9 patients in the active stage revealed weak (18)F-FDG accumulation (2.3 > or = SUV > or = 1.2). No significant (18)F-FDG accumulation was observed in the patients with inactive disease (SUV < or = 1.2) and 6 control healthy subjects (SUV < 1.3). Given the cutoff SUV is 1.3, the sensitivity of (18)F-FDG PET analysis of Takayasu arteritis is 90.9% and the specificity is 88.8%. (18)F-FDG PET coregistered with enhanced CT localized (18)F-FDG accumulation in the aortic wall in the patients with Takayasu arteritis who had weak (18)F-FDG accumulation that could not otherwise be identified anatomically. Finally, (18)F-FDG accumulation resolved with therapy in 2 active cases. The disappearance of (18)F-FDG accumulation did not coincide with the level of general inflammatory markers. CONCLUSION: The (18)F-FDG PET images coregistered with enhanced CT images showed the distribution and inflammatory activity in the aorta, its branches, and the pulmonary artery in patients with active Takayasu arteritis, even those who had weak (18)F-FDG accumulation. The intensity of accumulation decreased in response to therapy.

Adolescent↗

PubMed2004

Effects of local nicotinic activation of the superior colliculus on saccades in monkeys.

To examine the role of competitive and cooperative neural interactions within the intermediate layer of superior colliculus (SC), we elevated the basal SC neuronal activity by locally injecting a cholinergic agonist nicotine and analyzed its effects on saccade performance. After microinjection, spontaneous saccades were directed toward the movement field of neurons at the injection site (affected area). For visually guided saccades, reaction times were decreased when targets were presented close to the affected area. However, when visual targets were presented remote from the affected area, reaction times were not increased regardless of the rostrocaudal level of the injection sites. The endpoints of visually guided saccades were biased toward the affected area when targets were presented close to the affected area. After this endpoint effect diminished, the trajectories of visually guided saccades remained modestly curved toward the affected area. Compared with the effects on endpoints, the effects on reaction times were more localized to the targets close to the affected area. These results are consistent with a model that saccades are triggered by the activities of neurons within a restricted region, and the endpoints and trajectories of the saccades are determined by the widespread population activity in the SC. However, because increased reaction times were not observed for saccades toward targets remote from the affected area, inhibitory interactions in the SC may not be strong enough to shape the spatial distribution of the low-frequency preparatory activities in the SC.

Animals↗

PubMed2004

Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor. Unifying mechanisms have been implicated in the pathogenesis of polyQ-dependent neurodegenerative diseases including SBMA, Huntington disease and spinocerebellar ataxias. It has been suggested that mutant protein containing polyQ inhibits histone acetyltransferase activity, resulting in transcriptional dysfunction and subsequent neuronal dysfunction. Histone deacetylase (HDAC) inhibitors alleviate neurological phenotypes in fly and mouse models of polyQ disease, although the therapeutic effect is limited by the toxicity of these compounds. We studied the therapeutic effects of sodium butyrate (SB), an HDAC inhibitor, in a transgenic mouse model of SBMA. Oral administration of SB ameliorated neurological phenotypes as well as increased acetylation of nuclear histone in neural tissues. These therapeutic effects, however, were seen only within a narrow range of SB dosage. Our results indicate that SB is a possible therapeutic agent for SBMA and other polyQ diseases, although an appropriate dose should be determined for clinical application.

Acetylation↗

PubMed2004

High affinity D- and L-serine transporter Asc-1: cloning and dendritic localization in the rat cerebral and cerebellar cortices.

System asc transporter Asc-1, expressed in the brain, transports D- and L-serine with high affinity. To determine the localization of Asc-1 in the rat brain, we isolated a cDNA for the rat orthologue of Asc-1. The encoded protein designated as rAsc-1 (rat Asc-1) exhibited 98% sequence identity to mouse Asc-1 (mAsc-1). Based on amino acid sequences of rAsc-1 and mAsc-1, two polyclonal antibodies against Asc-1 were generated and used for the immunohistochemical analysis on the cerebral and cerebellar cortices of rats and mice. Asc-1 immunoreactivity was detected in neurons, including cerebellar Purkinje neurons and pyramidal neurons in the neocortex and hippocampus. It was clearly localized in dendrites as well as somata. The localization of Asc-1 in brain suggests the significant contribution of Asc-1 to amino acid mobilization in brains including the synaptic clearance of D-serine and the neuronal uptake of L-serine that is essential for survival and dendrite growth of Purkinje neurons in particular.

Amino Acid Sequence↗

PubMed2004

A quantitative analysis of the laminar distribution of synaptic boutons in field CA3 of the rat hippocampus.

We analyzed the laminar distribution of synaptic boutons in field CA3 of the rat hippocampus using a large montage electron micrograph. The size of boutons and synaptic vesicles was measured using a computer-assisted digitizing system. In all, 3353 synaptic boutons were observed in a 15 microm x 100 microm strip. Of these, 86.3% contained spherical vesicles (S-boutons), 12% contained flat vesicles (F-boutons), and 1.7% were mossy terminals (M-boutons). S-boutons were distributed widely in the strata moleculare (st. Mol), radiatum (st. Rad), and oriens (st. Ori), but there were only a few in the strata lucidum (st. Luc) and pyramidale (st. Pyr). The upper portions of both the st. Rad and Ori contained slightly fewer boutons. In terms of the location of synaptic contacts, 83% of all S-boutons were found on the dendritic spines and the rest were on the dendritic shafts. S-boutons on the dendritic shafts were observed more frequently in the st. Mol than in the other strata. According to the morphometry of the size of synaptic vesicles, S-boutons with small vesicles (mean vesicle area <1109 nm(2)) were located exclusively in the st. Mol, S-boutons with medium-sized vesicles (mean vesicle area 1109-1482 nm(2)) were observed in all strata, and S-boutons with large vesicles (mean vesicle area >1482 nm(2)) were distributed in the st. Luc and Ori, but not in the st. Mol. F-boutons were predominantly distributed in the upper half of the st. Mol and in the area around the st. Pyr, although they were observed in all strata. In the st. Mol, all the F-boutons were in contact with dendritic shafts, while near the st. Pyr, F-boutons were found exclusively on somata, the proximal parts of the dendritic shafts, and the initial segments of axons. The average F-bouton was smaller in the st. Mol (0.23 microm(2)) than near the st. Pyr (0.39 microm(2)). In this synapto-architectural study of the hippocampal CA3 region using large montage electron micrographs, we observed (1) an intimate relationship between synapse distribution and the dendritic structure of pyramidal neurons, (2) the distribution of different types of boutons containing vesicles of various size, and (3) two different plausible foci of postsynaptic inhibition where F-boutons were distributed densely, and (4) estimated the input ratios of pyramidal neurons.

Animals↗

PubMed2004

Switching between cortical and subcortical sensorimotor pathways.

It is well known that the reaction times of visually guided saccades exhibit a bimodal distribution. Those with extremely short reaction times are termed 'express saccades'. In their case, visual input appears to be transformed into motor output via a 'short-loop', brainstem-mediated pathway. In contrast, those with longer reaction times are called 'regular saccades'. The latter are presumably executed via a cortically mediated, 'long-loop' sensorimotor pathway. The 'gate' that switches signal flow between the short and long loop is thought to be located in between the superficial and deeper layers of the superior colliculus (SC). Nonlinear signal amplification mechanisms, which operate in local circuits of the deeper SC layers may underlie this gating function, with switching of the gate regulated in a context-dependent manner by inputs from the cerebral cortex and basal ganglia.

Animals↗

PubMed2004

Pedunculo-pontine control of visually guided saccades.

The cholinergic pedunculopontine tegmental nucleus (PPTN) is one of the major ascending arousal systems in the brainstem, and it is linked to motor, limbic and sensory centers. Despite an abundance of anatomical and physiological data, however, the functional role of PPTN neurons in behavioral control is still unresolved. In this chapter, we hypothesize that the PPTN is implicated in the integrative control of movement, particularly the reinforcement of tasks performed during conscious behavior. We present a new model of the PPTN's involvement in the control of arousal, attention and reinforcement aspects of motor behavior, with a focus on the control of saccadic eye movements.

Animals↗

PubMed2003

Macaque monkey retrosplenial cortex: II. Cortical afferents.

We investigated the cortical afferents of the retrosplenial cortex and the adjacent posterior cingulate cortex (area 23) in the macaque monkey by using the retrograde tracers Fast blue and Diamidino yellow. We quantitatively analyzed the distribution of labeled neurons throughout the cortical mantle. Injections involving the retrosplenial cortex resulted in labeled neurons within the retrosplenial cortex and in areas 23 and 31 (approximately 78% of the total labeled cells). In the remainder of the cortex, the heaviest projections originated in the hippocampal formation, including the entorhinal cortex, subiculum, presubiculum, and parasubiculum. The parahippocampal and perirhinal cortices also contained many labeled neurons, as did the prefrontal cortex, mainly in areas 46, 9, 10, and 11, and the occipital cortex, mainly area V2. Injections in area 23 also resulted in numerous labeled cells in the posterior cingulate and retrosplenial regions (approximately 67% of total labeled cells). As in the retrosplenial cortex, injections of area 23 led to many labeled neurons in the frontal cortex, although most of these cells were in areas 9 and 46. Larger numbers of retrogradely labeled cells were also distributed more widely in the posterior parietal cortex, including areas 7a, 7m, LIP, and DP. There were some labeled cells in the parahippocampal cortex. These connections are consistent with the retrosplenial cortex acting as an interface between the working memory functions in the prefrontal areas and the long-term memory encoding in the medial temporal lobe. The posterior cingulate cortex, in contrast, may be more highly associated with visuospatial functions.

Afferent Pathways↗

PubMed2003

Dynamic enhanced MRI of the subacromial bursa: correlation with arthroscopic and histological findings.

OBJECTIVE: To assess dynamic MRI with Gd-DTPA enhancement for evaluating inflammatory changes in the subacromial bursa. DESIGN AND PATIENTS: We detected the signal intensity changes in dynamic MRI of the subacromial bursa, and confirmed these macroscopically by arthroscopy and histologically. The signal intensity was measured using built-in software, and the enhancement ratio (E ratio) was calculated from dynamic MR images. In addition, as a parameter of the rate of the increase in the signal intensity from 0 to 80 s, the mean increase per second in the E ratio was obtained as the coefficient of enhancement (CE). The correlation was studied of the E ratio and CE with the arthroscopic findings (redness, villous formation, thickening and adhesion), and of the E ratio and CE with the histological findings (capillary proliferation, papillary hyperplasia, fibrosis and inflammatory cell infiltration) of the subacromial bursa. Of patients with shoulder pain, this study included those with rotator cuff injury; patients with rheumatoid arthritis or pitching shoulder disorders were excluded. There were 27 patients (15 men, 12 women) ranging in age from 25 to 73 years (mean 49.1 years). Dynamic MRI of the shoulder was also performed on the healthy side of 10 patients and in five normal young volunteers. RESULTS AND CONCLUSIONS: Changes in signal intensity on dynamic MRI were measured in the subacromial bursa. The E ratio (80 s) and CE (0-80 s) were significantly correlated with redness and villous formation as arthroscopic findings, positively correlated with capillary proliferation and papillary hyperplasia as histological findings (p < 0.05), and negatively correlated with fibrosis as a histological finding (p < 0.05) in the subacromial bursa. The patterns of dynamic curves were well correlated with the bursoscopic and histological findings of the synovium of the subacromial bursa. Dynamic MRI appears to correlate with inflammatory activity of synovium of the subacromial bursa. Clarifying the state of the synovium of the subacromial bursa may be useful in determining therapeutic strategies (e.g., indicating topical infusion of hyaluronic acid or steroids for preservative treatment and selecting the site). Furthermore, the evaluation may be useful for indicating surgery, selecting the technique, and evaluating preoperative and postoperative inflammatory changes.

Acromion↗

PubMed2003

Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease that affects males. It is caused by the expansion of a polyglutamine (polyQ) tract in androgen receptors. Female carriers are usually asymptomatic. No specific treatment has been established. Our transgenic mouse model carrying a full-length human androgen receptor with expanded polyQ has considerable gender-related motor impairment. This phenotype was abrogated by castration, which prevented nuclear translocation of mutant androgen receptors. We examined the effect of androgen-blockade drugs on our mouse model. Leuprorelin, a lutenizing hormone-releasing hormone (LHRH) agonist that reduces testosterone release from the testis, rescued motor dysfunction and nuclear accumulation of mutant androgen receptors in male transgenic mice. Moreover, leuprorelin treatment reversed the behavioral and histopathological phenotypes that were once caused by transient increases in serum testosterone. Flutamide, an androgen antagonist promoting nuclear translocation of androgen receptors, yielded no therapeutic effect. Leuprorelin thus seems to be a promising candidate for the treatment of SBMA.

Androgen Antagonists↗