Effects of Aerobic Exercise and Resistance Training on Cognitive Function: Comparative Study Based on FNDC5/Irisin/BDNF Pathway.

INTRODUCTION: Exercise has been recommended to suppress or prevent cognitive decline. Aerobic exercise (AE) may suppress cognitive decline via the fibronectin type III domain-containing protein 5 (FNDC5)/irisin/brain-derived neurotrophic factor (BDNF) pathway, and resistance training (RT) has a preventive effect on cognitive decline. However, the underlying mechanism remains unclear. This study verified the differences in the effects of AE and RT in suppressing and preventing cognitive decline based on the FNDC5/irisin/BDNF pathway. METHODS: We divided senescence-accelerated mouse-prone 8 into three groups: control (CON), AE, and RT and evaluated their memory during exercise intervention through a novel object recognition (NOR) task. We quantified FNDC5/irisin, mBDNF, and TrkB in the hippocampus using enzyme-linked immunosorbent assay and FNDC5 in skeletal muscle using Western blotting (WB). RESULTS: Behavioral analysis using NOR showed that values for both AE and RT were significantly greater than those for CON. WB analysis showed that the peripheral FNDC5 expression in the skeletal muscle was increased in AE. The expression levels of FNDC5/irisin and mBDNF in the hippocampus were significantly increased in both AE and RT compared with that in CON but that if TrkB was increased only in AE. CONCLUSION: No significant difference was observed between AE and RT in the inhibitory effect on age-related cognitive decline, and both groups were effective. The FNDC5/Irisin/BDNF pathway, which was the focus of this experiment, may be specific to AE. The mechanism that suppresses cognitive decline may differ depending on the type of exercise.

Exercise by Shaking Alleviates the Decline in Memory due to Aging: A Study in Mice.

INTRODUCTION: Although exercise can prevent cognitive decline due to aging, few elderly individuals are able to exercise for long. Therefore, an exercise method for older adults that is feasible for a long duration without overexertion is necessary. In this study, we focused on exercise by shaking. This study examined the possibility to prevent the decline in memory through regular and long-term shaking exercise using a senescence-accelerated mouse (SAM) model. Behavioral analysis was conducted, and histological changes in the mouse brain were examined to evaluate whether this stimulation method could become a novel exercise method. MATERIALS AND METHODS: The shaking exercise was applied to SAMP10 mice for 30 min 3 times per week for 25 continuous weeks. Behavioral analysis included a step-through passive avoidance test, whereas the histological analysis involved immunohistochemical staining using the anti-glutamate receptor (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors [AMPAR]) antibody in the hippocampus. The number and area of nerve cells in the hippocampal regions were measured and compared between groups. RESULTS: Behavioral analysis revealed that the shaking group retained memory longer than the control group, and memory capacity decline was suppressed. Additionally, histological examination showed that the shaking group had a higher number of AMPAR receptor-positive neurons per area in the hippocampal CA1 and CA3 regions than the control group, suggesting that degeneration and shedding of neurons due to aging was suppressed. DISCUSSION/CONCLUSION: We believe that shaking could become an exercise therapy that can reduce the decline in memory with aging and expect its human application in the future.

Endoscopic biliary drainage using a 4-Fr catheter for biliary obstruction: a pilot study.

INTRODUCTION: Stent or endoscopic nasobiliary drainage (ENBD) catheter placement for a tight, complicated biliary stricture is still technically challenging. A thin, 4-Fr ENBD catheter (4-Fr catheter) has been developed to overcome this difficulty. The study aimed to evaluate the feasibility of the 4-Fr catheter for endoscopic biliary drainage (EBD). MATERIAL AND METHODS: We performed a retrospective review of 51 patients who underwent EBD with the 4-Fr catheter because placement of a conventional drainage catheter (CDC) had failed. RESULTS: The success rate of 4-Fr catheter placement was 96.1% (49/51). The median patency period of the catheter was 114 days (95% CI, 53-200). Among the 49 patients with successful placement of the catheter, adverse events occurred in five (10.2%) patients: post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), two patients; catheter dislocation, one patient; and kinking of the 4-Fr catheter, two patients. Both cases of PEP improved with conservative treatment, but all cases of catheter dislocation and kinking required reintervention with a 4-Fr catheter. Forty-three (87.8%) patients achieved clinical remission after EBD with a 4-Fr catheter. CONCLUSIONS: The newly developed 4-Fr catheter is safe and feasible for EBD in patients in whom CDC placement is difficult due to a tight, complicated biliary stricture.

Maintaining Aging Hippocampal Function with Safe and Feasible Shaking Exercise in SAMP10 Mice.

INTRODUCTION: The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions. OBJECTIVE: The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise. METHODS: Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks. The motor function and hippocampal functions (learning, spatial cognition) of the mice were evaluated using behavioral experiments. The degree of hippocampal aging was evaluated based on brain morphology. The association between behavioral performance of the mice and the degree of hippocampal aging was then evaluated. RESULTS: The behavioral test results showed that the shaking group had higher motor coordination (p < 0.01) and motor learning (p < 0.05). Significantly higher performances in the learning ability were observed in the shaking group at a middle-period experiment (p < 0.05); the spatial cognitive functions also improved (p < 0.05). The shaking group showed delayed ageing of cells in the dentate gyrus (DG; area: p < 0.01) and cornu Ammonis (CA; area: p < 0.01) regions of the hippocampus. CONCLUSIONS: The shaking exercise enhances the activity of mice and reduces age-associated decreases in learning and spatial cognitive functions. Regarding hippocampal morphology, shaking exercise can prevent non-functional protein accumulation, cell atrophy, and cell loss. Specifically, shaking exercise protects cell growth and regeneration in the DG area and enhances the learning function of the hippocampus. Furthermore, shaking exercise maintained the spatial cognitive function of cells in the CA3 and CA1 regions, and prevented the chronic loss of CA2 transmission that decreased the spatial memory decline in mice.

Effect of exercise therapy on cytokine secretion in the saliva of bedridden patients.

[Purpose] The number of bedridden patients requiring nursing care in Japan has increased sharply in recent years because of its aging population and advances in medical care and has become a major social issue. Because bedridden patients are susceptible to nursing and healthcare-associated pneumonia, it is very important to improve their immunocompetence. Therefore, the effect of exercise therapy on stimulation of cytokine secretion in the saliva of bedridden patients was investigated. [Subjects and Methods] The subjects of this study were bedridden patients admitted to nursing care facilities. They were instructed to perform active assistive movement in the supine and sitting positions, with vital signs used as an index of the exercise load. Thirty-five patients fulfilled the inclusion criteria, which included cerebrovascular disease as the main cause of being bedridden and at least 6 months since onset. Interleukins were measured by enzyme-linked immunosorbent assay as immune mediators. [Results] Vital signs improved significantly after therapeutic exercise intervention, and the IL-6, IL-8, IL-15, and IL-17 levels also increased significantly after the intervention. [Conclusion] The results demonstrated that measurement of saliva samples may offer a safe minimally invasive method of measuring immune response in bedridden patients. This study suggests that exercise therapy may hold promise as an effective means of improving immunity in bedridden patients and may contribute to preventing aspiration pneumonia and promoting spontaneous recovery.

FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory.

As a passive motion and non-invasive treatment, theta-shaking exercise is considered an alternative to traditional active exercise for slowing down brain ageing. Here, we studied the influence of theta-shaking exercise on fibronectin type III domain containing 5/irisin (FNDC5/irisin) in the anterior nucleus of the thalamus, hippocampus, and medial prefrontal cortex (ATN-HPC-MPFC). Further, we assessed memory in senescence-accelerated prone mice (SAMP-10 mice) using a behavioural test to confirm the protective effect of theta-shaking exercise against age-related memory decline. SAMP-10 mice were subjected to theta-shaking exercise for 9-30 weeks. Mice then performed the T-maze test and passive avoidance task. Immunohistochemical analysis and ELISA were used to assess FNDC5/irisin, nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) expression in the ATN-HPC-MPFC. In the shaking group, FNDC5 was locally upregulated within the hippocampus and MPFC area rather than exhibiting even distribution throughout brain tissue. Irisin levels were generally higher in the control group. Meanwhile, hippocampal NGF levels were significantly higher in the shaking group, with no differences noted in neurotrophin levels. Theta-shaking preserved normal neurons in certain sub-regions. However, no beneficial changes in neuronal density were noted in the ATN. Theta-shaking exercise positively affects memory function in SAMP-10 mice. FNDC5 upregulation and higher levels of NGF, along with the potential involvement of irisin, may have contributed to the preservation of normal neuronal density in the hippocampus and MPFC subregions.

Stimulus in the form of rotation and shaking of a platform and its effect on the formation of trabecular bone in the lumbar vertebrae of mice.

BACKGROUND AND AIMS: Elderly individuals who suffer a fracture develop a gait disturbance and require prolonged bedrest. A fracture has a massive impact both physically and mentally and markedly diminishes quality of life. A new form of therapeutic exercise that mitigates the abrupt decrease in bone density in postmenopausal women must soon be developed so that those problems can be avoided. METHODS: The current study used a model of the decrease in bone density in ovariectomized mice to simulate postmenopausal women. The stimulus was provided by a shaking horizontal platform rotating in a circular motion. RESULTS: Comparison of the +/+ (ovariectomized/stimulated) group and +/- group indicated a significant decrease in BV/TV (p < 0.01), Tb.Th (p < 0.01), and Tb.N (p < 0.05) in the +/+ group and a significant increase in OV/BV (p < 0.01), OV/OS (p < 0.01), BFR/BV (p < 0.01), dLS/BS (p < 0.05), MS/BS (p < 0.05), BRs.R (p < 0.01), and Tb.Sp (p < 0.01) in the +/+ group. Physical therapy to prevent a decrease in bone density was studied via stimulus in the form of rotation of a platform. Analysis of bone histomorphometry revealed lessening of the decrease in bone density of the lumbar vertebrae, a feat that the stimulus from conventional physical therapy had failed to achieve. CONCLUSION: The current study delivered a shaking stimulus to mice in a model of postmenopause. Analysis of bone histomorphometry of the lumbar vertebrae suggested lessening of the abrupt decrease in bone density of trabecular bone. If this finding is used clinically, it could lead to physical therapy exercise that would be able to prevent compression fractures of the lumbar vertebrae.

[Current status of and regional differences in CKD management and medical cooperation in Japan: from the results of a nationwide questionnaire survey for primary care physicians].

OBJECTIVE: The goal of this study was to figure out the current status of and regional differences in CKD management and medical cooperation in Japan. METHODS: We conducted a nationwide questionnaire survey on CKD management for primary care physicians (PCPs) from December 2012 to March 2013. The questionnaire included 36 items about CKD management and medical cooperation. In order to compare the current status of CKD care and cooperation, we divided the country into 11 areas; Hokkaido, Tohoku, Kanto, Koshin-etsu, Hokuriku, Chubu-Tokai, Kinki, Chugoku, Shikoku, Kyushu and Okinawa. RESULTS: 28,200 sets of questionnaires were delivered to PCPs throughout Japan, and 2,287 (8.1%) doctors responded. Doctors at clinics accounted for 86.5%, and 90.9% were non-nephrologists. Regional differences were evident in the following items regarding CKD management; urinalysis at the first examination, measurement of urinary protein/albumin excretion, frequency of blood testing, counselling with eGFR, prescription of erythropoiesis stimulating agents (ESA). Urinalysis at the first examination was relatively rare in Koshin-etsu and Kanto (p < 0.01), and counseling with eGFR was relatively rare in Tohoku, Shikoku and Koshin-etsu (p = 0.05). Regional differences regarding medical cooperation were evident in the following items; functional level of cooperation, critical path, presence of consulting nephrologist, personal relationship, satisfaction with the nephrologists' reaction to referral, CKD involvement in Specific Medical Checkup/Specific Medical Guidance. Functional level of cooperation was higher in Chugoku, Okinawa, Chubu-Tokai and Hokuriku, and lower in Shikoku, Koshin-etsu and Kinki (p < 0.05). Serum creatinine measurement in the Specific Medical Checkup was involved more frequently in Okinawa, Shikoku, Kanto, Chubu-Tokai, Kyushu and Hokuriku, and less frequently in Tohoku, Chugoku and Kinki (p < 0.01). CONCLUSION: We elucidated the current status of CKD management by PCPs and medical cooperation in Japan. Effective actions to improve CKD care must be proposed on the basis of these data, especially the existing regional differences.

[Influence of physicians' subspecialty and training history on CKD management and medical cooperation: from the results of a nationwide questionnaire survey for primary care physicians].

OBJECTIVE: The goal of this study was to elucidate how the subspecialty and training history of primary care physicians(PCPs) influence CKD management and medical cooperation in Japan. METHODS: We conducted a nationwide questionnaire survey on CKD management for PCPs from December 2012 to March 2013. The questionnaire included 32 items about CKD management and medical cooperation. PCPs' subspecialties were categorized as follows: general internal medicine, nephrology, cardiology, diabetology/endocrinology, gastroenterology, pulmonology, neurology, neurosurgery, hematology, collagen disease/rheumatology, allergology. The PCPs' training history of nephrology was classified into three categories: none, experienced, active-nephrologist. Response distributions for each question were compared between the PCPs' subspecialties and the three categories of training history. RESULTS: 2,287 out of 28,200 PCPs (8.1%) of all 47 prefectures responded. The majority (86.5%) of responders were PCPs at clinics, and 90.9% were non-nephrologists. The PCPs' subspecialty influenced the response distributions in the following questions: utilization of the CKD guidebook, urinalysis at the first and follow-up examinations, frequency of blood testing, counselling with eGFR, self-monitoring of blood pressure, prescription and cessation of renin-angiotensin system (RAS) inhibitors, anemia treatment with erythropoiesis stimulating agents (ESA). The PCPs' training history of nephrology had a strong impact on various aspects of CKD management. The PCPs' subspecialties also influenced the responses regarding medical cooperation of CKD: relationship with nephrologists, utilization of critical path, criterion of patient referral, requests for nephrologists, discontent with the nephrologists' response. CONCLUSION: We elucidated that the PCPs' subspecialty and training history of nephrology substantially influenced CKD management and medical cooperation in Japan. Effective promotion activities to improve CKD management and medical cooperation should be proposed on the basis of these data.

[Evaluation of prototype for additional pad packing (polystyrene ball bullet) for homogenously fat suppressed magnetic resonance imaging].

PURPOSE: Homogeneity of static magnetic field (B(0)) is unstable for head and neck magnetic resonance (MR) examination; consequently, chemical shift selective fat suppression becomes inhomogeneous. There is a commercially available additional pad to attenuate the B(0) inhomogeneity, but it is expensive. It has been reported that uncooked rice can be used as a material in the pad, but it has hygienic and weight problems. We searched for a material which can replace the uncooked rice, and evaluated its performance. METHOD: After filling various materials into the cylindrical phantom, each material was evaluated by image distortion of gradient filed echo and spin echo single-shot echo planar images. A prototype additional pad was made with a material which showed less image distortion in the phantom experiment and is easily available in clinical examination. For comparison, an uncooked rice pad with the same volume was also prepared. Fat suppressed head and neck magnetic resonance imaging (MRI) of normal volunteers were visually compared when the three additional pads, including the commercial product, were used or not. RESULT: The polystyrene ball bullet (BB bullet) was adopted as a material for the additional pad. The improvement of the fat suppression in the head and neck MRI was almost the same between the three additional pads. BB bullet pad was the lightest. CONCLUSION: BB bullet can be used as a material of additional pad attenuating the B(0) inhomogeneity instead of uncooked rice.

Review of the health-promoting effects of exercise and the involvement of myokines.

Exercise reduces the risk of obesity-based, lifestyle-related diseases, such as metabolic abnormalities and cardiovascular diseases. The present review covers the health-promoting effects of exercise from the point of view of the physiologically active factor myokine, which is secreted by skeletal muscle, and focuses on the skeletal muscle as a new endocrine organ. Myokines have various effects, such as preventing metabolic syndrome by breaking down fat, preventing diabetes by improving glucose metabolism, and preventing progression of arteriosclerosis, dementia, and osteoporosis by enhancing bone metabolism. These substances also stabilize blood pressure, prevent cancer, increase immunity against infections, and prevent the development of age-associated diseases. Myokines are secreted by skeletal muscle into blood vessels, allowing them to exert systemic endocrine effects in organs throughout the body. Myokines are involved in bodily homeostasis and adaptation to the environment, and function by a mechanism similar to that of the skeletal muscle mass regulatory mechanism. Determining the relationships between multiple organs and their biological significance is important for exercise and health research. Progress in this field is expected to result in the identification of pathological mechanisms of action, development of new drugs, evaluation of the effectiveness of biomarkers over a wide range, and future improvement in healthcare.

Novel shaking exercises for hippocampal and medial prefrontal cortex functioning maintain spatial working memory.

INTRODUCTION: The decline in spatial working memory is one of the earliest signs of normal brain aging. OBJECTIVE: We developed a novel physical exercise method, termed the "shaking exercise," to slow down this process. METHODS: The experimental protocol included administering the shaking exercise for 8-32 weeks in male senescence-accelerated mouse prone 10 (SAMP-10). They were subjected to the T-maze test, followed by immunohistochemical analysis, to assess the influence of the shaking exercise on the M1 muscarinic acetylcholine receptor (CHRM1) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) of the dorsal hippocampus and medial prefrontal cortex (dHC-mPFC). RESULTS: The T-maze test demonstrated that the shaking group had less hesitation in the face of selecting direction at week 24. In the immunohistochemical analysis, more CHRM1s were in the CA3 subregion and more AMPARs were in the subiculum. CHRM1s and AMPARs were maintained in the CA1 region and the mPFC. The CHRM1s seem to have a positive effect on the AMPAR in the dentate gyrus (DG) region and the CA3 region. In the CA1 region, CHRM1s were negatively correlated with AMPARs. In addition, high-density neurons were expressed in the shaking group in the upstream DG, the middle part and the distal part of CA3, the distal part of CA1, and the mPFC. CONCLUSIONS: Our results raise the possibility that maintenance of the spatial working memory effect observed with the shaking exercise is driven in part by the uneven affection of CHRM1s and AMPARs in the dHC-mPFC circuit system and significantly maintains the neuronal expression in the dHC-mPFC.

Exercise through Shaking Stimuli Suppresses Cancer Growth via the Wnt pathway in ApcMin/+ Mice.

OBJECTIVE: Exercise has been reported to suppress colorectal cancer; however, the mechanism of suppression by exercise and its effect on the Wnt pathway, which is particularly involved in the early stage of carcinogenesis, remain unclear. In this study, we subjected ApcMin/+ mice to exercise by shaking stimuli to investigate the mechanisms of suppressing colorectal cancer, and focused on the Ca2+ pathway, which is one of the ß-catenin-independent Wnt signaling pathways that suppress the accumulation of ß-catenin. METHODS: Mice in the exercise group were subjected to exercise by shaking stimuli for 30 min/session, 6 sessions/ week, for a total of 11 weeks. The number and diameter of intestinal polyps were calculated. Expression analysis of ß-catenin and Pak1 from the intestinal tract and Wnt5a-Pan and Wnt5a-Long from the gastrocnemius muscle was performed by western blotting. The expression of ß-catenin and Wnt5a-Pan was observed by immunohistochemical staining. RESULT: The levels of expression of ß-catenin and Pak1 in the small intestine were low in the exercise group, indicating that exercise suppressed the accumulation of ß-catenin. In the gastrocnemius muscle, the levels of expression of Wnt5a-Pan and Wnt5a-Long were significantly higher in the exercise group (p < 0.05). Histological analysis revealed that the percentage of large polyps was significantly lower in the exercise group than in the control group (p < 0.01), revealing that exercise suppressed the growth of polyps. In addition, the villi/crypt ratio (V/C ratio) was significantly higher in the exercise group, suggesting the suppression of exercise-induced local inflammation in the small intestine. CONCLUSION: We believe that the mechanism of polyp growth suppression is related to the inflammatory and not the Wnt pathway. This study clarified the growth-suppressing effect of a novel exercise method on cancer. We believe that its development and clinical application might open new possibilities for the prevention treatment of colorectal cancer.

Polymorphisms of the 22q11.2 breakpoint region influence the frequency of de novo constitutional t(11;22)s in sperm.

The constitutional t(11;22) is the most frequent recurrent non-Robertsonian translocation in humans, the breakpoints of which are located within palindromic AT-rich repeats on 11q23 and 22q11 (PATRR11 and PATRR22). Genetic variation of the PATRR11 was found to affect de novo t(11;22) translocation frequency in sperm derived from normal healthy males, suggesting the hypothesis that polymorphisms of the PATRR22 might also influence the translocation frequency. Although the complicated structure of the PATRR22 locus prevented determining the genotype of the PATRR22 in each individual, genotyping of flanking markers as well as identification of rare variants allowed us to demonstrate an association between the PATRR22 allele type and the translocation frequency. We found that size and symmetry of the PATRR22 affect the de novo translocation frequency, which is lower for the shorter or more asymmetric versions. These data lend support to our hypothesis that the PATRRs form secondary structures in the nucleus that induce genomic instability leading to the recurrent translocation.

Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes.

The events that take place during the prophase of meiosis I are essential for the correct segregation of homologous chromosomes. Defects in these processes likely contribute to infertility or recurrent pregnancy loss in humans. To screen for candidate genes for reproductive failure due to meiotic defects, we have analyzed the gene expression patterns in fetal, neonatal and adult gonads of both male and female mice by microarray and thereby identified 241 genes that are expressed specifically during prophase of meiosis I. Combined with our previous data obtained from developing spermatocytes, a total of 99 genes were identified that are upregulated in early prophase I. We confirmed the meiotic prophase I-specific expression of these genes using qRT-PCR. To further screen this panel for candidate genes that fulfill important roles in homologous pairing, synapsis and recombination, we established a gene transfer system for prophase I oocytes in combination with in vitro organ culture of ovaries, and successfully determined the localization of the selected genes. This gene set can thus serve as a resource for targeted sequence analysis via next-generation sequencing to identify the genes associated with human reproduction failure due to meiotic defects.

Use-dependent increase in attention to the prosthetic foot in patients with lower limb amputation.

Patients with lower limb amputation experience "embodiment" while using a prosthesis, perceiving it as part of their body. Humans control their biological body parts and receive appropriate information by directing attention toward them, which is called body-specific attention. This study investigated whether patients with lower limb amputation similarly direct attention to prosthetic limbs. The participants were 11 patients with lower limb amputation who started training to walk with a prosthesis. Attention to the prosthetic foot was measured longitudinally by a visual detection task. In the initial stage of walking rehabilitation, the index of attention to the prosthetic foot was lower than that to the healthy foot. In the final stage, however, there was no significant difference between the two indexes of attention. Correlation analysis revealed that the longer the duration of prosthetic foot use, the greater the attention directed toward it. These findings indicate that using a prosthesis focuses attention akin to that of an individual's biological limb. Moreover, they expressed that the prosthesis felt like a part of their body when they could walk independently. These findings suggest that the use of prostheses causes integration of visual information and movement about the prosthesis, resulting in its subjective embodiment.

Global gene expression profiling in early-stage polycystic kidney disease in the Han:SPRD Cy rat identifies a role for RXR signaling.

Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5-fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found nine pathways in common between 3- and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated "Vitamin D Receptor (VDR)/Retinoid X Receptor (RXR) Activation," "LPS/IL-1-Mediated Inhibition of RXR Function," and "Liver X Receptor (LXR)/RXR Activation." These results suggest that RXR-mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the upregulation of Ptx2, Alox15b, OSP, and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed in both the nucleus and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR-mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.

Maintenance of the Amygdala-Hippocampal Circuit Function with Safe and Feasible Shaking Exercise Therapy in SAMP-10 Mice.

INTRODUCTION: Patients with dementia show reduced adaptive, behavioral, and physiological responses to environmental threats. Physical exercise is expected to delay brain aging, maintain cognitive function and, consequently, help dementia patients face threats and protect themselves skillfully. METHODS: To confirm this, we aimed to investigate the effects of the shaking exercise on the avoidance function in the senescence-accelerated mouse-prone strain-10 (SAMP-10) model at the behavioral and tissue levels. SAMP-10 mice were randomized into 2 groups: a control group and a shaking group. The avoidance response (latency) of the mice was evaluated using a passive avoidance task. The degree of amygdala and hippocampal aging was evaluated based on the brain morphology. Subsequently, the association between avoidance response and the degree of amygdala-hippocampal aging was evaluated. RESULTS: Regarding the passive avoidance task, the shaking group showed a longer latency period than the control group (p < 0.05), even and low intensity staining of ubiquitinated protein, and had a higher number of and larger neurons than those of the control group. The difference between the groups was more significant in the BA region of the amygdala and the CA1 region of the hippocampus (staining degree: p < 0.05, neuron size: p < 0.01, neuron counts: p < 0.01) than in other regions. CONCLUSIONS: The shaking exercise prevents nonfunctional protein (NFP) accumulation, neuron atrophy, and neuron loss; delays the aging of the amygdala and hippocampus; and maintains the function of the amygdala-hippocampal circuit. It thus enhances emotional processing and cognition functions, the memory of threats, the skillful confrontation of threats, and proper self-protection from danger.

Body-Specific Attention to the Hands and Feet in Healthy Adults.

To execute the intended movement, the brain directs attention, called body-specific attention, to the body to obtain information useful for movement. Body-specific attention to the hands has been examined but not to the feet. We aimed to confirm the existence of body-specific attention to the hands and feet, and examine its relation to motor and sensory functions from a behavioral perspective. The study included two groups of 27 right-handed and right-footed healthy adults, respectively. Visual detection tasks were used to measure body-specific attention. We measured reaction times to visual stimuli on or off the self-body and calculated the index of body-specific attention score to subtract the reaction time on self-body from that off one. Participants were classified into low and high attention groups based on each left and right body-specific attention index. For motor functions, Experiment 1 comprised handgrip strength and ball-rotation tasks for the hands, and Experiment 2 comprised toe grip strength involved in postural control for the feet. For sensory functions, the tactile thresholds of the hands and feet were measured. The results showed that, in both hands, the reaction time to visual stimuli on the hand was significantly lesser than that offhand. In the foot, this facilitation effect was observed in the right foot but not the left, which showed the correlation between body-specific attention and the normalized toe gripping force, suggesting that body-specific attention affected postural control. In the hand, the number of rotations of the ball was higher in the high than in the low attention group, regardless of the elaboration exercise difficulty or the left or right hand. However, this relation was not observed in the handgripping task. Thus, body-specific attention to the hand is an important component of elaborate movements. The tactile threshold was higher in the high than in the low attention group, regardless of the side in hand and foot. The results suggested that more body-specific attention is directed to the limbs with lower tactile abilities, supporting the sensory information reaching the brain. Therefore, we suggested that body-specific attention regulates the sensory information to help motor control.

Two different forms of palindrome resolution in the human genome: deletion or translocation.

Regions containing palindromic sequence are known to be susceptible to genomic rearrangement in prokaryotes and eukaryotes. Palindromic AT-rich repeats (PATRR) are hypervariable in the human genome, manifesting size polymorphisms and a propensity to rearrange. Size variations are mainly the result of internal deletions, while two PATRRs on 11q23 and 22q11 (PATRR11 and 22) contribute to generation of the t(11;22), a recurrent constitutional translocation. In this study, we analyzed the PATRR11 sequence of numerous polymorphic alleles in detail. Various types of shorter variants are likely derived from the most frequent approximately 450 bp PATRR11 by deletion. Deletion variants possess a significant number of identical nucleotides at their two endpoints, indicating the possible involvement of direct repeats within the PATRR11. Rare variants with insertional alterations involve AT-rich sequences of unknown origin. This is in contrast to palindrome-mediated translocations between PATRRs that manifest smaller deletions and only a limited number of identical nucleotides at the breakpoints. Further, we identified a rare translocation product that has a non-AT-rich insertion of a transcribed gene segment at the translocation breakpoint. Our data suggest that the outcomes of palindrome-mediated re-arrangements reflect distinct molecular pathways; intra-palindrome re-arrangements are possibly dictated by a replication slippage or microhomology-directed repair pathway, and inter-palindrome translocations are likely driven by non-homologous end joining.