Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity.

The Topoisomerase 3B (Top3b) - Tudor domain containing 3 (Tdrd3) protein complex is the only dual-activity topoisomerase complex that can alter both DNA and RNA topology in animals. TOP3B mutations in humans are associated with schizophrenia, autism and cognitive disorders; and Top3b-null mice exhibit several phenotypes observed in animal models of psychiatric and cognitive disorders, including impaired cognitive and emotional behaviors, aberrant neurogenesis and synaptic plasticity, and transcriptional defects. Similarly, human TDRD3 genomic variants have been associated with schizophrenia, verbal short-term memory and educational attainment. However, the importance of Tdrd3 in normal brain function has not been examined in animal models. Here we generated a Tdrd3-null mouse strain and demonstrate that these mice display both shared and unique defects when compared to Top3b-null mice. Shared defects were observed in cognitive behaviors, synaptic plasticity, adult neurogenesis, newborn neuron morphology, and neuronal activity-dependent transcription; whereas defects unique to Tdrd3-deficient mice include hyperactivity, changes in anxiety-like behaviors, olfaction, increased new neuron complexity, and reduced myelination. Interestingly, multiple genes critical for neurodevelopment and cognitive function exhibit reduced levels in mature but not nascent transcripts. We infer that the entire Top3b-Tdrd3 complex is essential for normal brain function, and that defective post-transcriptional regulation could contribute to cognitive and psychiatric disorders.

RNA-binding protein Nocte regulates Drosophila development by promoting translation reinitiation on mRNAs with long upstream open reading frames.

RNA-binding proteins (RBPs) with intrinsically disordered regions (IDRs) are linked to multiple human disorders, but their mechanisms of action remain unclear. Here, we report that one such protein, Nocte, is essential for Drosophila eye development by regulating a critical gene expression cascade at translational level. Knockout of nocte in flies leads to lethality, and its eye-specific depletion impairs eye size and morphology. Nocte preferentially enhances translation of mRNAs with long upstream open reading frames (uORFs). One of the key Nocte targets, glass mRNA, encodes a transcription factor critical for differentiation of photoreceptor neurons and accessory cells, and re-expression of Glass largely rescued the eye defects caused by Nocte depletion. Mechanistically, Nocte counteracts long uORF-mediated translational suppression by promoting translation reinitiation downstream of the uORF. Nocte interacts with translation factors eIF3 and Rack1 through its BAT2 domain, and a Nocte mutant lacking this domain fails to promote translation of glass mRNA. Notably, de novo mutations of human orthologs of Nocte have been detected in schizophrenia patients. Our data suggest that Nocte family of proteins can promote translation reinitiation to overcome long uORFs-mediated translational suppression, and disruption of this function can lead to developmental defects and neurological disorders.

Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity.

The Topoisomerase 3B (Top3b) - Tudor domain containing 3 (Tdrd3) protein complex is the only dual-activity topoisomerase complex in animals that can alter the topology of both DNA and RNA. TOP3B mutations in humans are associated with schizophrenia, autism and cognitive disorders; and Top3b-null mice exhibit several phenotypes observed in animal models of psychiatric and cognitive disorders, including impairments in cognitive and emotional behaviors, aberrant neurogenesis and synaptic plasticity, and transcriptional defects. Similarly, human TDRD3 genomic variants have been associated with schizophrenia, verbal shorten-memory and learning, and educational attainment. However, the importance of Tdrd3 in normal brain function has not been examined in animal models. Here we built a Tdrd3-null mouse strain and demonstrate that these mice display both shared and unique defects when compared to Top3b-null mice. Shared defects were observed in cognitive behaviors, synaptic plasticity, adult neurogenesis, newborn neuron morphology, and neuronal activity-dependent transcription; whereas defects unique to Tdrd3-deficient mice include hyperactivity, changes in anxiety-like behaviors, increased new neuron complexity, and reduced myelination. Interestingly, multiple genes critical for neurodevelopment and cognitive function exhibit reduced levels in mature but not nascent transcripts. We infer that the entire Top3b-Tdrd3 complex is essential for normal brain function, and that defective post-transcriptional regulation could contribute to cognitive impairment and psychiatric disorders.

A dual-activity topoisomerase complex promotes both transcriptional activation and repression in response to starvation.

Topoisomerases are required to release topological stress generated by RNA polymerase II (RNAPII) during transcription. Here, we show that in response to starvation, the complex of topoisomerase 3b (TOP3B) and TDRD3 can enhance not only transcriptional activation, but also repression, which mimics other topoisomerases that can also alter transcription in both directions. The genes enhanced by TOP3B-TDRD3 are enriched with long and highly-expressed ones, which are also preferentially stimulated by other topoisomerases, suggesting that different topoisomerases may recognize their targets through a similar mechanism. Specifically, human HCT116 cells individually inactivated for TOP3B, TDRD3 or TOP3B topoisomerase activity, exhibit similarly disrupted transcription for both starvation-activated genes (SAGs) and starvation-repressed genes (SRGs). Responding to starvation, both TOP3B-TDRD3 and the elongating form of RNAPII exhibit concomitantly increased binding to TOP3B-dependent SAGs, at binding sites that overlap. Notably, TOP3B inactivation decreases the binding of elongating RNAPII to TOP3B-dependent SAGs while increased it to SRGs. Furthermore, TOP3B-ablated cells display reduced transcription of several autophagy-associated genes and autophagy per se. Our data suggest that TOP3B-TDRD3 can promote both transcriptional activation and repression by regulating RNAPII distribution. In addition, the findings that it can facilitate autophagy may account for the shortened lifespan of Top3b-KO mice.

Natural behaviours after guided growth for idiopathic genu valgum correction: comparison between percutaneous transphyseal screw and tension-band plate.

BACKGROUND: Percutaneous epiphysiodesis using a transphyseal screw (PETS) or tension-band plating (TBP) has shown favourable correction results; however, the physeal behaviours in terms of rebound, stable correction, or overcorrection after guided growth have not been completely understood. In patients with idiopathic genu valgum, we therefore asked: (1) How is the correction maintained after implant removal of guided growth? (2) Is there any difference in the natural behaviours after PETS or TBP removal at the femur and tibia? METHODS: We retrospectively reviewed 73 skeletally immature limbs with idiopathic genu valgum treated with PETS or TBP. PETS was performed in 23 distal femurs and 13 proximal tibias, and TBP was performed in 27 distal femurs and ten proximal tibias. Mechanical axis deviation (MAD), mechanical lateral distal femoral angle (mLDFA), and mechanical medial proximal tibial angle were measured at pre-correction, implant removal, and final follow-up. Changes of ≤ 3° in mechanical angles after implant removal were considered stable. Comparisons between the implant, anatomical site, and existence of rebound were performed. RESULTS: The mean MAD improved from - 18.8 mm to 11.3 mm at implant removal and decreased to -0.2 mm at the final follow-up. At the final follow-up, 39 limbs (53.4%) remained stable and only 12 (16.4%) were overcorrected. However, 22 limbs (30.1%) showed rebound. TBP was more common, and the correction period was longer in the rebound group (p < 0.001 and 0.013, respectively). In femurs treated with PETS, the mean mLDFA increased from 86.9° at implant removal to 88.4° at the final follow-up (p = 0.031), demonstrating overcorrection. However, a significant rebound from 89.7° to 87.1° was noted at the femur in the TBP group (p < 0.001). The correction of the proximal tibia did not change after implant removal. CONCLUSION: The rebound was more common than overcorrection after guided growth; however, approximately half the cases demonstrated stable correction. The overcorrection occurred after PETS in the distal femur, while cases with TBP had a higher probability of rebound. The proximal tibia was stable after implant removal. The subsequent physeal behaviours after each implant removal should be considered in the guided growth.

Real-Time Stress Analysis Affecting Nurse during Elective Spinal Surgery Using a Wearable Device.

Successful spinal surgery demands high levels of concentration and cooperation from participating health care workers. The intraoperative stress levels and concentration levels of surgeons have been studied previously; however, those of nurses are rarely studied. Therefore, the purpose of this study is to understand the stresses affecting surgical nurses by their participating role during spinal surgery. A total of 160 surgical stress records were obtained during 40 surgeries, including electroencephalography (EEG) signals and heart rate variability (HRV) from three orthopedic spinal surgeons and six nurses; concentration, tension level and physical stress were analyzed. Levels of both concentration and tension were significantly higher in circulating nurses during all surgical stages (p < 0.05). Both beats per minute and low frequency/high frequency ratios, which reflect physical stress, were higher in scrub nurses (p < 0.05). As the surgical experience of scrub nurses increased, the key parameters related to stress tended to decrease (p < 0.01). These results will contribute to understanding the pattern of intraoperative stress of surgical nurses, and therefore help in enhancing the teamwork of the surgical team for optimal outcomes.

A dual-activity topoisomerase complex regulates mRNA translation and turnover.

Topoisomerase 3ß (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation-enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is partly linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B-TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity.

Efficient, Light-Driven Reduction of CO2 to CO by a Carbon Monoxide Dehydrogenase-CdSe/CdS Nanorod Photosystem.

The solar conversion of CO2 to low carbon fuels has been heralded as a potential solution to combat the rise in greenhouse gas emissions. Here we report the first light-driven activation of [NiFe] CODH II from Carboxydothermus hydrogenoformans for the reduction of CO2 to CO. To accomplish this, a hybrid photosystem composed of CODH II and CdSe/CdS dot-in-rod nanocrystals was developed. By incorporating a low-potential redox mediator to assist electron transfer, quantum yields up to 19% and turnover frequencies of 9 s-1 were achieved. These results represent a new standard in efficient CO2 reduction by an enzyme-based photocatalytic systems. Furthermore, successful photoactivation of CODH II allows for future exploration into the enzyme's not fully understood mechanism.

Concomitant Talocalcaneal Coalition as a Risk Factor for Early Relapse Following Ponseti Treatment of Idiopathic Clubfoot.

Concomitant talocalcaneal coalition (TCC) in idiopathic clubfeet is not well documented in the literature. The purpose of this study was to describe our experience with very early relapsing idiopathic clubfeet associated with TCC. Although cases have been successfully treated with the Ponseti casting method, all recurred within 2 months of removing the final cast. A single-centre cohort of twelve feet in eight patients treated by a single surgeon between 2006 and 2020 was investigated retrospectively. Recurred cavus with variable degrees of equinus was the earliest findings noted. TCC was incidentally detected during the open reduction of the earliest three feet in our series. Afterwards, ultrasonography was advised as a screening tool for detecting an associated anomaly; however, only the use of magnetic resonance imaging (MRI) was 100% accurate in diagnosing concurrent TCC. All coalitions were cartilaginous and the posterior facet was most commonly involved facet. The average age was 18 months for the coalition resection and open reduction of a dislocated talonavicular joint, and the average duration of follow-up was 52 months. None of the patients showed clinical signs of relapse at the latest follow-up. We recommend that an associated TCC should be considered in very early relapsing idiopathic clubfoot cases.

Effect of the Osteotomy Inclination Angle in the Sagittal Plane on the Posterior Tibial Slope of the Tibiofemoral Joint in Medial Open-Wedge High Tibial Osteotomy: Three-Dimensional Computed Tomography Analysis.

The posterior tibial slope of the tibiofemoral joint changes after medial open wedge high tibial osteotomy (MOWHTO), but little is known about the effect of the sagittal osteotomy inclination angle on the change in the posterior tibial slope of the tibiofemoral joint. The purpose of this study was to investigate the effect of the osteotomy inclination angle in the sagittal plane on changes in the posterior tibial slope after MOWHTO by comparing how anterior and posterior inclination affect the posterior tibial slope of the tibiofemoral joint. The correlation between the osteotomy inclination angle and the postoperative posterior tibial slope angle was also assessed. Between May 2011 and November 2017, 80 patients with medial compartment osteoarthritis who underwent MOWHTO were included. The patients were divided into two groups according to the sagittal osteotomy inclination angle on the 3D reconstructed model. Patients with an osteotomy line inclined anteriorly to the medial tibial plateau line were classified into group A (58 patients). Patients with posteriorly inclined osteotomy line were classified as group P (22 patients). In the 3D reconstructed model, the preoperative and postoperative posterior tibial slope, osteotomy inclination angle relative to medial tibial plateau line in sagittal plane, and gap distance and ratio of the anterior and posterior osteotomy openings were measured. The preoperative and postoperative hip-knee-ankle angle, weight-bearing line ratio, and posterior tibial slope were also measured using plain radiographs. In the 3D reconstructed model, the postoperative posterior tibial slope significantly increased in group A (preoperative value = 9.7 ± 2.9°, postoperative value = 10.7 ± 3.0°, p < 0.001) and decreased in group P (preoperative value = 8.7 ± 2.7°, postoperative value = 7.7 ± 2.7°, p < 0.001). The postoperative posterior tibial slope (group A = 10.7 ± 3.0°, group P = 7.7 ± 2.7°, p < 0.001) and posterior tibial slope change before and after surgery (group A = 1.0 ± 0.8°, group P = -0.9 ± 0.8°, p < 0.001) also differed significantly between the groups. The Pearson correlation coefficient was 0.875 (p < 0.001) for the osteotomy inclination angle, and multivariate regression analysis showed that the only significant factor among the variables was the sagittal osteotomy inclination angle (ß coefficient = 0.216, p < 0.001). The posterior tibial slope changed according to the osteotomy inclination angle in the sagittal plane after MOWHTO. The postoperative posterior tibial slope tended to increase when the osteotomy line was inclined anteriorly with respect to the medial tibial plateau line but decreased when the osteotomy line was inclined posteriorly. To avoid inadvertent change of posterior tibial slope, close attention needs to be paid to maintaining the sagittal osteotomy line parallel to the medial joint line during MOWHTO.

Topoisomerase 3ß knockout mice show transcriptional and behavioural impairments associated with neurogenesis and synaptic plasticity.

Topoisomerase 3ß (Top3ß) is the only dual-activity topoisomerase in animals that can change topology for both DNA and RNA, and facilitate transcription on DNA and translation on mRNAs. Top3ß mutations have been linked to schizophrenia, autism, epilepsy, and cognitive impairment. Here we show that Top3ß knockout mice exhibit behavioural phenotypes related to psychiatric disorders and cognitive impairment. The mice also display impairments in hippocampal neurogenesis and synaptic plasticity. Notably, the brains of the mutant mice exhibit impaired global neuronal activity-dependent transcription in response to fear conditioning stress, and the affected genes include many with known neuronal functions. Our data suggest that Top3ß is essential for normal brain function, and that defective neuronal activity-dependent transcription may be a mechanism by which Top3ß deletion causes cognitive impairment and psychiatric disorders.

Roles of Topoisomerases in Heterochromatin, Aging, and Diseases.

Heterochromatin is a transcriptionally repressive chromatin architecture that has a low abundance of genes but an enrichment of transposons. Defects in heterochromatin can cause the de-repression of genes and transposons, leading to deleterious physiological changes such as aging, cancer, and neurological disorders. While the roles of topoisomerases in many DNA-based processes have been investigated and reviewed, their roles in heterochromatin formation and function are only beginning to be understood. In this review, we discuss recent findings on how topoisomerases can promote heterochromatin organization and impact the transcription of genes and transposons. We will focus on two topoisomerases: Top2α, which catenates and decatenates double-stranded DNA, and Top3ß, which can change the topology of not only DNA, but also RNA. Both enzymes are required for normal heterochromatin formation and function, as the inactivation of either protein by genetic mutations or chemical inhibitors can result in defective heterochromatin formation and the de-silencing of transposons. These defects may contribute to the shortened lifespan and neurological disorders observed in individuals carrying mutations of Top3ß. We propose that topological stress may be generated in both DNA and RNA during heterochromatin formation and function, which depend on multiple topoisomerases to resolve.

QUANTIFICATION OF THE KAERI'S MOVABLE NEUTRON IRRADIATOR BY USING A 6LiI(Eu) SCINTILLATOR.

There is no standardised on-site calibration system for performance testing and calibration of neutron area monitors although there is a mobile irradiation device as like a neutron howitzer. For this reason, neutron area monitors, which legally and periodically require calibration in Korea, are removed from the installation location and tested at the Korea Atomic Energy Research Institute (KAERI) or the Korea Research Institute of Standards and Science (KRISS). To test the possibility of an on-site performance calibration system, the KAERI manufactured a movable neutron irradiator. The movable neutron irradiator is composed of high-density polyethylene and has an overall size of 50 cm (L) × 50 cm (W) × 46 cm (H). In this study, the neutron fields generated by the movable neutron irradiator were quantified at distances of 80, 100, 120, and 140 cm from the centre of the source. Quantification was performed using the initially estimated neutron spectrum from the computer simulation, the count rate data measured using a 6LiI(Eu) scintillator combined with a Bonner sphere spectrometer (BSS), and the response function of the BSS. As a result of the quantification of the neutron field at each distance, the fractions of scattered neutrons to total neutron fluence were almost constant within 5%.

Topoisomerase 3ß interacts with RNAi machinery to promote heterochromatin formation and transcriptional silencing in Drosophila.

Topoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3ß represents a family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3ß interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP. Top3ß and RISC mutants are similarly defective in heterochromatin formation and transcriptional silencing by position-effect variegation assay. Moreover, both Top3ß and AGO2 mutants exhibit reduced levels of heterochromatin protein HP1 in heterochromatin. Furthermore, expression of several genes and transposable elements in heterochromatin is increased in the Top3ß mutant. Notably, Top3ß mutants defective in either RNA binding or catalytic activity are deficient in promoting HP1 recruitment and silencing of transposable elements. Our data suggest that Top3ß may act as an RNA topoisomerase in siRNA-guided heterochromatin formation and transcriptional silencing.

Publisher Correction: Composition, diversity and bioactivity of culturable bacterial endophytes in mountain-cultivated ginseng in Korea.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Enzymatic synthesis of avermectin B1a glycosides for the effective prevention of the pine wood nematode Bursaphelenchus xylophilus.

Avermectin produced by Streptomyces avermitilis is an anti-nematodal agent against the pine wood nematode Bursaphelenchus xylophilus. However, its potential usage is limited by its poor water solubility. For this reason, continuous efforts are underway to produce new derivatives that are more water soluble. Here, the enzymatic glycosylation of avermectin was catalyzed by uridine diphosphate (UDP)-glycosyltransferase from Bacillus licheniformis with various UDP sugars. As a result, the following four avermectin B1a glycosides were produced: avermectin B1a 4″-ß-D-glucoside, avermectin B1a 4″-ß-D-galactoside, avermectin B1a 4″-ß-L-fucoside, and avermectin B1a 4″-ß-2-deoxy-D-glucoside. The avermectin B1a glycosides were structurally analyzed based on HR-ESI MS and 1D and 2D nuclear magnetic resonance spectra, and the anti-nematodal effect of avermectin B1a 4″-ß-D-glucoside was found to exhibit the highest activity (IC50 = 0.23 µM), which was approximately 32 times greater than that of avermectin B1a (IC50 = 7.30 µM), followed by avermectin B1a 4″-ß-2-deoxy-D-glucoside (IC50 = 0.69 µM), avermectin B1a 4″-ß-L-fucoside (IC50 = 0.89 µM), and avermectin B1a 4″-ß-D-galactoside (IC50 = 1.07 µM). These results show that glycosylation of avermectin B1a effectively enhances its in vitro anti-nematodal activity and that avermectin glycosides can be further applied for treating infestations of the pine wood nematode B. xylophilus.

EVALUATION OF NEUTRON SCATTERING CORRECTION USING THE SEMI-EMPIRICAL METHOD AND THE SHADOW-CONE METHOD FOR THE NEUTRON FIELD OF THE KOREA ATOMIC ENERGY RESEARCH INSTITUTE.

When neutron survey metres are calibrated in neutron fields, the results for room- and air-scattered neutrons vary according to the distance from the source and the size, shape and construction of the neutron calibration room. ISO 8529-2 recommends four approaches for correcting these effects: the shadow-cone method, semi-empirical method, generalised fit method and reduced-fitting method. In this study, neutron scattering effects are evaluated and compared using the shadow-cone and semi-empirical methods for the neutron field of the Korea Atomic Energy Research Institute (KAERI). The neutron field is constructed using a 252Cf neutron source positioned in the centre of the neutron calibration room. To compare the neutron scattering effects using the two correction methods, measurements and simulations are performed using respectively KAERI's Bonner sphere spectrometer (BBS) and Monte Carlo N-Particle code at twenty different positions. Neutron spectra are measured by a europium-activated lithium iodide [6LiI(Eu)] scintillator in combination with the BBS. The calibration factors obtained using each methods show good agreement within 1.1%.

LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis.

Some long noncoding RNAs (lncRNAs) can regulate gene expression programs, in turn affecting specific cellular processes. We sought to identify the mechanism through which the lncRNA OIP5-AS1, which is abundant in the cytoplasm, suppressed cell proliferation. Silencing of OIP5-AS1 in human cervical carcinoma HeLa cells triggered the appearance of many aberrant (monopolar, multipolar, misaligned) mitotic spindles. Through a combination of approaches to pull down mRNAs bound to OIP5-AS1 and identify proteins differentially expressed when OIP5-AS1 was silenced, we identified a subset of human cell cycle regulatory proteins encoded by mRNAs that interacted with OIP5-AS1 in HeLa cells. Further analysis revealed that GAK mRNA, which encodes a cyclin G-associated kinase important for mitotic progression, associated prominently with OIP5-AS1. The interaction between these two transcripts led to a reduction in GAK mRNA stability and GAK protein abundance, as determined in cells in which OIP5-AS1 levels were increased or decreased. Importantly, the aberrant mitotic cell division seen after silencing OIP5-AS1 was partly rescued if GAK was simultaneously silenced. These findings indicate that the abnormal mitoses seen after silencing OIP5-AS1 were caused by an untimely rise in GAK levels and suggest that OIP5-AS1 suppresses cell proliferation at least in part by reducing GAK levels.

Corrigendum: Correction of the unit for stone size in the ABSTRACT and RESULTS section. The Gachon University Ureteral Narrowing score: A comprehensive standardized system for predicting necessity of ureteral dilatation to treat proximal ureteral calculi.

[This corrects the article on p. 280 in vol. 57.].

Treadmill exercise ameliorates intracerebral hemorrhage-induced depression in rats.

Intracerebral hemorrhage (ICH) is a severe type of stroke causing neurological dysfunction with high mortality rate. Depression is one of the most common complications of ICH. In the present study, the effects of treadmill exercise on ICH-induced depressive symptoms in relation with apoptosis were investigated using rats. ICH rat model was induced by injection of collagenase into the hippocampus using stereotaxic instrument. Open field test for activity and forced swimming test for depressive symptoms were conducted. Apoptosis in the hippocampus was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3, and western blot for Bcl-2 and Bax. Western blot analysis for 5-hydroxy-tryptamine (5-HT, serotonin) and tryptophan hydroxylase (TPH) in the dorsal raphe was also conducted for biomarkers of depression. In the present results, immobility time was increased and climbing time was decreased by induction of ICH and treadmill exercise inhibited immobility time and increased climbing time in ICH rats. DNA fragmentation and caspase-3 expression in the hippocampal dentate gyrus were enhanced by induction of ICH and treadmill exercise suppressed ICH-induced DNA fragmentation and caspase-3 expression. Bax expression in the hippocampus was increased by induction of ICH and treadmill exercise inhibited Bax expression in the ICH rats. Expressions of 5-HT and TPH in the dorsal raphe were decreased by induction of ICH and treadmill exercise increased expressions of 5-HT and TPH in the ICH rats. In the present study, treadmill exercise ameliorated depressive symptoms through inhibiting apoptosis.