Hidemi Fujino

Exercise exerts neuroprotective effects on Parkinson's disease model of rats

Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinsons disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinsons disease model of rats with subsequent improvement in deteriorated motor function.

Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis

Bedridden patients who receive good physical rehabilitation are able to exhibit clinical improvement. Accumulating evidence demonstrates that exercise increases endogenous neurogenesis and may even protect against central nervous system (CNS) disorders. Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs above the ground and unloading the weights in these extremities. In addition, the effects of exercise and recovery time with normal caging after HS were also explored. BrdU (50 mg/kg, i.p.) was injected every 8 h over the last 4 days of each paradigm to label proliferative cells. Immunohistochemical results revealed that HS significantly reduced the number of BrdU/Doublecortin double-positive cells in the subventricular zone and dentate gyrus. Exercise and recovery time significantly improved atrophy of the soleus muscle, but did not attenuate the HS-induced decrement in BrdU/Dcx-positive cells. A separate cohort of animals was exposed to the same HS paradigm and enzyme-linked immunosorbent assay (ELISA) of neurotrophic factors was performed on brain tissue samples harvested at the end of the HS period, as well as plasma samples from all animals. ELISA results revealed that HS reduced the levels of brain-derived neurotrophic factor in the hippocampus and vascular endothelial growth factor plasma levels. This study revealed that lack of exercise reduced neurogenesis with downregulation of neurotrophic factors. The use of the HS model in conjunction with CNS disease models should further elucidate the role of exercise in neurogenesis and neurotrophic factors in neurologic disorders.

Hyperbaric oxygen exposure improves blood glucose level and muscle oxidative capacity in rats with type 2 diabetes.

BACKGROUND The effects of exposure to hyperbaric oxygen on blood glucose level and muscle oxidative capacity in rats with type 2 diabetes were investigated. METHODS Five-week-old male Goto-Kakizaki rats were divided into four groups: normobaric (NN; exposed to 21% oxygen at 760 mm Hg for 8 weeks), hyperbaric to normobaric (HN; exposed to 36% oxygen at 950 mm Hg for 4 weeks, followed by 21% oxygen at 760 mm Hg for 4 weeks), normobaric to hyperbaric (NH; exposed to 21% oxygen at 760 mm Hg for 4 weeks, followed by 36% oxygen at 950 mm Hg for 4 weeks), and hyperbaric (HH; exposed to 36% oxygen at 950 mm Hg for 8 weeks). RESULTS Blood glucose levels were lower in the HN, NH, and HH groups than in the NN group. Up-regulated mRNA expression levels of peroxisome proliferator-activated receptor-gamma co-activator-1alpha were observed in the soleus muscles of the HN, NH, and HH groups and in the plantaris muscles of the HN and HH groups. The soleus muscles of the NN group contained only type I fibers, whereas those of the HN, NH, and HH groups contained type I, type IIA, and type IIC fibers. An increased percentage of type I fibers and a decreased percentage of type IIB fibers were observed in the plantaris muscles of the NH, HN, and HH groups. CONCLUSIONS Exposure to hyperbaric oxygen reduces high blood glucose levels and improves oxidative capacities in the skeletal muscles of rats with diabetes, and these effects are maintained under normobaric conditions even after exposure to hyperbaric oxygen.

PGC-1α mRNA level and oxidative capacity of the plantaris muscle in rats with metabolic syndrome, hypertension, and type 2 diabetes

We examined the fiber profiles and the mRNA levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β) and of the PPARγ coactivator-1α (PGC-1α) in the plantaris muscles of 15-week-old control (WR), metabolic syndrome (CP), hypertensive (SHR), and type 2 diabetic (GK) rats. The deep regions in the muscles of SHR and GK rats exhibited lower percentages of high-oxidative type I and IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR and CP rats. The surface regions in the muscles of CP, SHR, and GK rats exhibited lower percentages of high-oxidative type IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR rats. The muscles of SHR and GK rats had lower oxidative enzyme activity compared with WR rats. The muscles of SHR rats had the lowest PPARδ/β mRNA level. In addition, the muscles of SHR and GK rats had lower PGC-1α mRNA level compared with WR and CP rats. We concluded that the plantaris muscles of rats with hypertension and type 2 diabetes have lower oxidative capacity, which is associated with the decreased level of PGC-1α mRNA.

Protective effects of astaxanthin on capillary regression in atrophied soleus muscle of rats

The capillary regression in skeletal muscles associated with a chronic decrease in activity is related to a dysfunction of endocapillary cells induced by over‐expression of oxidative stress. We hypothesized that treatment with astaxanthin, an antioxidant, would attenuate the oxidative stress induced by decreased skeletal muscle use, and that this attenuation would prevent the associated capillary regression. The purpose of the present study was to investigate the antioxidant and preventive effects of astaxanthin on capillary regression in the soleus muscle during hindlimb unloading.

Protective effects of exercise preconditioning on hindlimb unloading-induced atrophy of rat soleus muscle

Aim:  A chronic decrease in the activation and loading levels of skeletal muscles as occurs with hindlimb unloading (HU) results in a number of detrimental changes. Several proteolytic pathways are involved with an increase in myofibrillar protein degradation associated with HU. Exercise can be used to counter this increase in proteolytic activity and, thus, may be able to protect against some of the detrimental changes associated with chronic decreased use. The purpose of the present study was to determine the potential of a single bout of preconditioning endurance exercise in attenuating the effects of 2 weeks of HU on the mass, phenotype and force‐related properties of the soleus muscle in adult rats.

Gene Expression Levels of Heat Shock Proteins in the Soleus and Plantaris Muscles of Rats after Hindlimb Suspension or Spaceflight

Gene expression levels of heat shock proteins (HSPs) in the slow-twitch soleus and fast-twitch plantaris muscles of rats were determined after hindlimb suspension or spaceflight. Male rats were hindlimb-suspended for 14 d or exposed to microgravity for 9 d. The mRNA expression levels of HSP27, HSP70, and HSP84 in the hindlimb-suspended and microgravity-exposed groups were compared with those in the controls. The mRNA expression levels of the 3 HSPs in the soleus muscle under normal conditions were higher compared with those in the plantaris muscle. The mRNA expression levels of the 3 HSPs in the soleus muscle were inhibited by hindlimb suspension and spaceflight. The mRNA expression levels of the 3 HSPs in the plantaris muscle did not change after hindlimb suspension. It is suggested that the mRNA expression levels of the 3 HSPs are regulated by the mechanical and neural activity levels, and therefore the decreased mRNA expression levels of HSPs in the slow-twitch muscle following hindlimb suspension and spaceflight are related to a reduction in the mechanical and neural activity levels.

Effects of Hyperbaric Oxygen on Metabolic Capacity of the Skeletal Muscle in Type 2 Diabetic Rats with Obesity

We investigated whether hyperbaric oxygen enhances the oxidative metabolic capacity of the skeletal muscle and attenuates adipocyte hypertrophy in type 2 diabetic rats with obesity. Five-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as diabetic animals and nondiabetic controls, respectively, and assigned to control and hyperbaric oxygen groups. Animals in the hyperbaric oxygen group were exposed to an atmospheric pressure of 1.25 with an oxygen concentration of 36% for 3 h daily. The glucose level at 27 weeks of age was significantly higher in OLETF rats than in LETO rats, but the elevation was inhibited in OLETF rats exposed to hyperbaric oxygen. The slow-to-fast fiber transition in the skeletal muscle was observed in OLETF rats, but the shift was inhibited in OLETF rats exposed to hyperbaric oxygen. Additionally, the oxidative enzyme activity of muscle fibers was increased by hyperbaric oxygen. The adipocyte size was larger in OLETF rats than in LETO rats, but hypertrophied adipocytes were not observed in OLETF rats exposed to hyperbaric oxygen. Hyperbaric oxygen enhances glucose and lipid metabolism in the skeletal muscle, indicating that hyperbaric oxygen can prevent elevation of glucose and adipocyte hypertrophy in diabetic rats with obesity.

Effects of Hyperbaric Oxygenation on Blood Pressure Levels of Spontaneously Hypertensive Rats

Five-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to hyperbaric oxygenation with an enhanced atmospheric pressure (950 mmHg) and an increased oxygen concentration (36%) for 6 h per day. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored for 8 weeks of hyperbaric oxygenation period. After 8 weeks of hyperbaric oxygenation, the derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potentials (BAPs) were measured. After 5 weeks of hyperbaric oxygenation, the hyperbaric group of WKY exhibited lower SBP than the age-matched normobaric group, while there were no differences in the DBP between the normobaric and hyperbaric groups. After 3 and 7 weeks of hyperbaric oxygenation, the hyperbaric group of SHR exhibited lower SBP and DBP than the age-matched normobaric group. The hyperbaric groups of both WKY and SHR exhibited lower dROMs than the respective normobaric groups. There were no differences in BAPs between the normobaric and hyperbaric groups of WKY. In contrast, the hyperbaric group of SHR exhibited higher BAPs than the normobaric group. We conclude that the hyperbaric oxygenation conditions used in this study effectively repress hypertension.

Differences in capillary architecture, hemodynamics, and angiogenic factors in rat slow and fast plantarflexor muscles

The capillary architecture in skeletal muscles is unique in that it has anastomoses that interconnect individual capillaries.