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Background The mortality of acute ischemic stroke patients caused by vertebrobasilar artery occlusion (VBAO) is high and mechanical thrombectomy has gradually become a promising treatment for acute ischemic stroke. This study analyzed the efficacy of mechanical thrombectomy and the risk factors associated with poor outcomes in VBAO patients caused by severe local atherosclerotic stenosis. Methods This retrospective study enrolled patients with acute ischemic stroke caused by VBAO between March 1, 2016 and August 31, 2019. Patient demographic and clinical data were collected retrospectively. All enrolled patients were retrospectively interviewed for at least 3 months. Patients with a modified Rankin scale (mRS) score between 0 and 3 points were defined as having satisfactory outcomes while those with more than 3 points were defined as having unsatisfactory outcomes. In-hospital mortality, the rates of recanalization, and the rates of intracerebral hemorrhage were also recorded. Multivariable logistic regression was used to determine the risk factors of unsatisfactory outcomes in enrolled patients. Results A total of 65 patients were enrolled in this study with a median age 69.0 (63.0-78.0) years and 48 patients (73.8%) were male. Approximately 50% of patients had a mRS score of 0 or 1 point within 90 days after treatment with mechanical thrombectomy and 14 patients had a mRS score of 6 points. A total of 11 patients died in hospital. Out of the 65 patients, 7 required recanalization and 9 patients suffered from intracerebral hemorrhage. Multivariate logistic regression analysis showed that older age, lower baseline posterior circulation acute stroke prognosis early CT score (pcASPECTS), higher baseline National Institutes of Health stroke scale (NIHSS) score, and residual stenosis were independent risk factors of both unsatisfactory outcomes and mortality of VBAO patients. Conclusions This study confirmed the important role of mechanical thrombectomy in the treatment of acute ischemic stroke caused by VBAO and may provide some guidance for improving the prognosis of patients.

Aging is a process associated with blood-brain barrier (BBB) damage and the reduction in neurogenesis, and is the greatest known risk factor for neurodegenerative disorders. However, the effects of Fe

Background: Bachelor of Medicine and Bachelor of Surgery (MBSS) students are the largest group of international students. Due to the breakout of COVID-19, most international students have returned to their home countries. From March 2020, the MBBS undergraduate students of Yangzhou University were taught online since March 2020. For MBBS students，the effect of online teaching remains unknown. Methods: This study was conducted in Yangzhou University in June 2021, including 295 MBBS international undergraduate students. The objective conditions, environment, teacher factors, personal factors, advantages, and disadvantages of online teaching were evaluated for each student by using a self-completed structured anonymous questionnaire. At the same time, Pearson chi-square analysis was conducted to evaluate the factors affecting online teaching satisfaction (teaching attitude, teacher-student interaction, teacher evaluation, learning effect, online teaching management). Results: Most students’ hardware was well equipped and their network could meet the need of online learning (240 of 280, 85.71%). Most students (263 of 280, 93.93%) had a quiet environment during online teaching. With respect to factors conducive to online teaching, students rated the importance of teachers from the aspects of knowledge level, teaching methods, class attitude, interaction with students, English proficiency, homework correction and pre-class guidance. In terms of students' attention, 76.78% students' attention was concentrated and 85.36% students had a positive attitude towards online teaching. Four factors (teaching attitude, teacher-student interaction, learning effect and management of online teaching) appeared to be associated with teaching effect satisfaction. Conclusion: This study investigates the various factors involved in conducting online education during the pandemic and provides suggestions for improving the quality and effectiveness of online education for MBBS students.

Most intracerebral hemorrhage (ICH) survivors have poor long-term outcomes, such as cognitive deficits and depression. Delayed lesions of ICH include neuron loss and white matter injury and the pathology of the lesions involves iron deposition and glial responses, which contribute to depressive-like behavior and cognitive impairment in animals. This study aimed to investigate the effects of FTY720 (0.3 mg/kg/day for 4 weeks) on iron deposition, glial responses, histological abnormalities and behavioral dysfunction in mice with ICH. The primary adverse long-term outcomes in our study of ICH mice were depressive-like behavior and impaired recognition memory. We found that FTY720 safely ameliorated depressive-like behavior and impaired recognition without affecting recovery of grip function and locomotor activity 28 days post-ICH. Moreover, we measured neuron loss, white matter lesions, lesion volume and iron deposition at day 28, which were attenuated in the FTY720-treated group compared to the ICH-control group, without changing initial hematoma volume on day 1 post-ICH. Long-term elevation of glial responses, including microglia activity and astrogliosis with tumor necrosis factor alpha (TNFα) expression was demonstrated by Western blot and immunofluorescence staining, which we found was attenuated by FTY720 treatment. Hence, FTY720 could become a novel therapeutic agent for improving long-term outcomes after ICH.

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been seen in the pathological states of many disorders such as ischemic diseases and cancers. Many natural compounds (NCs) have long been recognized to ameliorate oxidative stress due to their inherent antioxidant activities. The modulation of oxidative stress by NCs via activating the Nrf2 signaling pathway is summarized in the review. Three NCs, ursolic acid, betulinic acid, and curcumin, and the mechanisms of their cytoprotective effects are investigated in myocardial ischemia, cerebral ischemia, skin cancer, and prostate cancer. To promote the therapeutic performance of NCs with poor water solubility, the formulation approach, such as the nano drug delivery system, is elaborated as well in this review.

Aging is a process associated with blood–brain barrier (BBB) damage and the reduction in neurogenesis, and is the greatest known risk factor for neurodegenerative disorders. However, the effects of Fe3O4 nanozymes on neurogenesis have rarely been studied. This study examined the effects of Fe3O4 nanozymes on neuronal differentiation in the dentate gyrus (DG) and BBB integrity of D-galactose-induced aged mice. Long-term treatment with Fe3O4 nanozymes (10 μg/mL diluted in ddH2O daily) markedly increased the doublecortin (DCX) immunoreactivity and decreased BBB injury induced by D-galactose treatment. In addition, the decreases in the levels of antioxidant proteins including superoxide dismutase (SOD) and catalase as well as autophagy-related proteins such as Becin-1, LC3II/I, and Atg7 induced by D-galactose treatment were significantly ameliorated by Fe3O4 nanozymes in the DG of the mouse hippocampus. Furthermore, Fe3O4 nanozyme treatment showed an inhibitory effect against apoptosis in the hippocampus. In conclusion, Fe3O4 nanozymes can relieve neuroblast damage and promote neuroblast differentiation in the hippocampal DG by regulating oxidative stress, apoptosis, and autophagy.

Background: The number of international medical students studying in China has largely increased over the past decades. However, few studies have addressed the difficulties that the international medical students face and there is a dearth of information on understanding the difficulties these students confront during their social integration in host countries. Therefore, the aim of this study was to investigate the international medical students’ difficulties to build social networks during their studying overseas. Methods: This study was designed primarily with the aim of enhancing understanding of the International Bachelor of Medicine and Bachelor of Surgery (MBBS) students’ difficulties in social networks building. 26 MBBS students from year-3 and year-4 were asked by the question: what are the difficulties to establish the social networks you face? Thematic analysis was conducted by MAXQDA. Results: The result of the individual interviews revealed that language barriers, (lack of) communication skills, personality factors, intercultural differences and study pressure were key factors that hindered the MBBS students’ adaptation to the Chinese culture and social networks building in China. Conclusions: This study reveals several potential coping strategies which could promote the social inclusion and cultural integration of the MBBS students, including providing interactive language training programs, organizing diverse programs enhancing intercultural communication, maintaining strong support networks and endeavoring the MBBS students to actively engage themselves in their learning and living environments. In conclusion, the provision of interactive learning environments, diverse social network opportunities and, moreover, maintaining social support and nurturing cultural integration, would greatly promote social integration and benefit international medical students.

Lipopolysaccharide (LPS) has been used as a reagent for a model of systemic inflammatory response. Ribosomal protein S3 (rpS3) is a multi-functional protein that is involved in transcription, metastasis, DNA repair, and apoptosis. In the present study, we examined the changes of rpS3 immunoreactivity in the mouse hippocampus after systemic administration of 1 mg/kg of LPS. From 6 h after LPS treatment, rpS3 immunoreactivity was decreased in pyramidale cells of the hippocampus proper (CA1-CA3 regions) and in granule cells of the dentate gyrus. At this point in time, rpS3 immunoreactivity began to increase in non-pyramidal cells and non-granule cells. From 1 day after LPS treatment, rpS3 immunoreactivity in pyramidal and granule cells was hardly detected; however, strong rpS3 immunoreactivity was shown in non-pyramidal and non-granule cells. Based on double immunofluorescence staining for rpS3/ionized calcium-binding adapter 1 (Iba-1, a marker for microglia) and glial fibrillary acidic protein (GFAP, a marker for astrocytes), strong rpS3 immunoreactivity was expressed in Iba-1-immunoreactive microglia, not in GFAP-immunoreactive astrocytes, at 1 and 2 days after LPS treatment. These results indicate that rpS3 immunoreactivity changes only in pyramidal and granule cells, and rpS3 is expressed only in activated microglia after LPS treatment: this may be associated with the neuroinflammatory responses in the brain.

The forkhead box O (FoxO) proteins regulate processes ranging from cell longevity to cell apoptosis and function as transcription factors. FoxO3a is expressed throughout the brain including the hippocampus. In the present study, we investigated the changes in FoxO3a immunoreactivity and its protein levels in the gerbil hippocampal CA1 region after 5 min of transient global cerebral ischemia. FoxO3a immunoreactivity and protein levels in the ischemic CA1 region, which is very vulnerable to ischemic damage, were slightly decreased from 3 h after ischemia-reperfusion (I-R) and maintained until 12 h after I-R. One and 2 days after I-R, FoxO3a immunoreactivity and protein levels were similar to those in the sham-operated group. At 3 days after I-R, FoxO3a immunoreactivity and protein levels were markedly increased in the CA1 region. FoxO3a immunoreactivity was hardly detected in pyramidal neurons from 5 days after I-R; however, at 5 days after I-R, FoxO3a immunoreactivity was detected in astrocytes and GABAergic interneurons of the ischemic CA1 region. These results indicate that both FoxO3a immunoreactivity and protein levels are distinctively altered in the ischemic CA1 region after transient cerebral ischemia, and that the changes in FoxO3a expression may be related to the ischemia-induced delayed neuronal death.

Cyclooxygenase-2 (COX-2) is believed to be a multifunctional neural modulator that affects synaptic plasticity in the hippocampus. In the present study, we investigated the differential effects of treadmill exercise on COX-2 immunoreactivity in the dentate gyrus in early and chronic diabetic stages in Zucker diabetic fatty (ZDF) rats and lean control (ZLC) rats. To this end, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day for 5 consecutive days at 16-22 m/min for 5 weeks or 12-16 m/min for 7 weeks, respectively. Treadmill exercise in prediabetic and chronic diabetic rats significantly reduced blood glucose levels. In particular, exercise in the prediabetic rat blocked the onset of diabetes. COX-2 immunoreactivity was mainly detected in the granule cell layer of the dentate gyrus and stratum pyramidale of the CA3 region in all groups. COX-2 immunoreactivity was significantly increased in these regions of ZLC and ZDF rats after treadmill exercise in the early diabetic stage. However, COX-2 immunoreactivity was not changed in these regions in ZDF rats after treadmill exercise in the chronic stage. These results suggest that treadmill exercise in diabetic animals in the chronic stage has limited ability to cause plasticity in the dentate gyrus.

In the present study, we investigated the effects of treadmill exercise in early and chronic diabetic stages on parvalbumin (PV) immunoreactivity in the subgranular zone of the dentate gyrus of Zucker diabetic fatty (ZDF) and its lean control rats (ZLC). To investigate the effects, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day/5 consecutive days at 16-22 m/min for 5 weeks or 12-16 m/min for 7 weeks, respectively. Physical exercise in pre-diabetic rats prevented onset of diabetes, while exercise in rats at chronic diabetic stage significantly reduced blood glucose levels. In addition, physical exercise in the pre-diabetic rats significantly increased PV immunoreactive fibers in the strata oriens and radiatum of the CA1-3 region and in the polymorphic and molecular layers of the dentate gyrus compared to that in sedentary controls. However, in rats at chronic stages, PV immunoreactivity was slightly increased in the CA1-3 region as well as in the dentate gyrus compared to that in the sedentary controls. These results suggest that physical exercise has differential effects on blood glucose levels and PV immunoreactivity according to diabetic stages. Early exercise improves diabetic phenotype and PV immunoreactive fibers in the rat hippocampus.

Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damages in the brain. In the present study, ischemia-induced changes in GLP-1R immunoreactivity in the gerbil hippocampal CA1 region were evaluated after transient cerebral ischemia; in addition, the neuroprotective effect of the GLP-1R agonist exendin-4 (EX-4) against ischemic damage was studied. GLP-1R immunoreactivity and its protein levels in the ischemic CA1 region were highest at 1 day after ischemia/reperfusion (I/R). At 4 days after I/R, GLP-1R immunoreactivity was hardly detected in CA1 pyramidal neurons, and its protein level was lowest. GLP-1R protein level was increased again at 10 days after I/R, and GLP-1R immunoreactivity was found in astrocytes and GABAergic interneurons. In addition, EX-4 treatment attenuated ischemia-induced hyperactivity, neuronal damage, and microglial activation in the ischemic CA1 region in a dose-dependent manner. EX-4 treatment also induced the elevation of GLP-1R immunoreactivity and protein levels in the ischemic CA1 region. These results indicate that GLP-1R is altered in the ischemic region after an ischemic insult and that EX-4 protects against ischemia-induced neuronal death possibly by increasing GLP-1R expression and attenuating microglial activation against transient cerebral ischemic damage.

The extract of Alpinia katsumadai, a member of the family Zingiberaceae, shows anti-inflammatory effects and antioxidant activity. We observed the neuroprotective effects of the extract from Alpinia katsumadai seed (EAKS) against ischemic damage in gerbils administered oral EAKS (25, and 50 mg/kg) once a day for 7 days before transient cerebral ischemia. In the 50 mg/kg EAKS-treated ischemia group, about 67% of neurons in the hippocampal CA1 region (CA1) survived after ischemia/reperfusion (I/R) based on cresyl violet staining. We observed that EAKS treatment significantly maintained brain-derived neurotrophic factor (BDNF) immunoreactivity in the ischemic CA1 region after I/R. In addition, protein levels of BDNF in the 50 mg/kg EAKS-treated ischemia group were much higher than those in the vehicle-treated ischemia group after I/R. These findings indicate that repeated supplementation of EAKS protects neurons from ischemic damage, such that BDNF is distinctively maintained in ischemic areas.

Lipopolysaccharide (LPS) induces a strong immune response, and pretreatment with low dose of LPS suppresses the production of proinflammatory mediators. In the present study, we investigated the effect of LPS preconditioning on the delayed neuronal death in the gerbil hippocampal CA1 region after 5 min of transient cerebral ischemia. LPS preconditioning showed neuroprotective effects against ischemic damage in the hippocampal CA1 region after ischemic insult: about 92% of neurons in the CA1 region survived in the LPS-treated ischemia group. LPS preconditioning maintained anti-inflammatory cytokines, such as interleukin (IL)-4 and IL-13, in pyramidal neurons in the CA1 region after ischemia/reperfusion. In addition, IL-4 and IL-13 protein levels in the CA1 region of the LPS-treated ischemia group were similar to the vehicle-treated sham group. We found that reactive gliosis was markedly attenuated in the CA1 region of the LPS-treated ischemia group compared to the vehicle-treated ischemia group using immunohistochemistry of glial fibrillary acidic protein for astrocytes, and ionized calcium-binding adapter molecule 1 and isolectin B4 for microglia. These results indicate that LPS preconditioning may provide neuroprotection in the ischemic hippocampal CA1 region via maintenance of anti-inflammatory cytokines and suppression of glial activation.

Cyclooxygenase (COX) is a rate-limiting enzyme in synthesis of prostaglandins from arachidonic acid. In this study, we observed the effects of a physical exercise on COX-2 immunoreactivity in the hippocampus using immunohistochemistry in rats. In addition, we examined effects of administration of a COX-2 inhibitor, celecoxib, on neuroblast differentiation. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1 h/session/day for 5 weeks. The running speed was gradually increased from 16 to 22 m/min with 2 m/min per 2 weeks. In the ZLC and ZDF rats, COX-2 immunoreaction was detected in the granule cell layer of the dentate gyrus and in the stratum pyramidale of the CA2/3 region; COX-2 immunoreaction in the CA1 region was hardly detected. In the exercised-ZLC and ZDF rats, COX-2 immunoreactivity was significantly increased compared to that in the ZLC and ZDF rats, showing that COX-2 immunoreactivity in the exercised-ZDF rats was slightly low than that in the exercised-ZDF rats. In addition, weak COX-2 immunoreactivity was shown in the CA1 region by exercise. On the other hand, the repeated oral administration of celecoxib to 4-week-old ZDF rats significantly decreased the neuroblasts in the subgranular zone of the dentate gyrus. These results suggest that COX-2 may be associated with the increase of synaptic plasticity or contacts in the hippocampus.

Capsaicin has effects on the adiposity by increasing energy and lipid metabolism, and decreases appetite and fat intake. In the present study, we investigated changes in food intake and body weight after capsaicin treatment. We also observed changes in orexigenic and anorexigenic neuropeptides-agouti-related peptide (AgRP), alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotropic hormone (ACTH) and orexin-immunoreactivities in the rat hypothalamus after capsaicin administration. Only one day after capsaicin treatment, the mean food intake was significantly decreased. There was no significant difference in the mean body weight between vehicle- and capsaicin-treated groups. In addition, after capsaicin treatment, numbers of AgRP- and orexin-immunoreactive ((+)) cells were significantly decreased in the arcuate nucleus (ARC) and lateral hypothalamic area, respectively. In contrast, the number of alpha-MSH(+) and ACTH(+) cells in the ARC of the capsaicin-treated rats was higher than in the vehicle-treated rats. These results indicate that capsaicin reduces food intake, not body weight, transiently, and decreases AgRP and orexin immunoreactivities, whereas it increases alpha-MSH and ACTH immunoreactivities in rat hypothalamic nuclei.

Oxidative stress is one of predisposing factors to age-related neurodegeneration in the brain. In particular, thiol-containing groups are susceptible to oxidative stress, which induces the formation of the disulfide bond and/or hyperoxidized form of thiol-containing proteins. We observed the protein thiol levels in the hippocampal homogenates and also investigated changes in hyperoxidized form of peroxiredoxin (Prx-SO(3)) immunoreactivity and proteins levels in the gerbil hippocampal subregions during normal aging. Levels of total thiol, non-protein thiol, and protein thiol were decreased in the hippocampal homogenates with age. At post-natal month 1 (PM 1), pyramidal and non-pyramidal cells in the hippocampal CA1 region (CA1) showed Prx-SO(3) immunoreactivity. Prx-SO(3) immunoreactivity in the cells was decreased by PM 12, thereafter, Prx-SO(3) immunoreactivity in the cells increased again with age. In the CA2/3, Prx-SO(3) immunoreactivity in pyramidal cells was not significantly changed; however, the immunoreactivity in pyramidal cells was very low at PM 12. Prx-SO(3) immunoreactivity in the dentate gyrus (DG) was distinctly changed during aging. At PM 1, Prx-SO(3) immunoreactivity in granule and polymorphic cells was weak and strong, respectively. The immunoreactivity in the neurons was decreased with age, not shown in any neurons at PM 12. Thereafter, Prx-SO(3) immunoreactivity increased again with age. In addition, Prx-SO(3) protein level in the hippocampus was lowest at PM 12. These results suggest that thiol-containing proteins are changed during aging and Prx-SO(3) immunoreactivity was different according to cells in the hippocampal subregion during aging.

In the present study, we investigated the effects of a treadmill exercise on serum glucose levels and Ki67 and doublecortin (DCX) immunoreactivity, which is a marker of cell proliferation expressed during cell cycles except G0 and early G1 and a marker of progenitors differentiating into neurons, respectively, in the subgranular zone of the dentate gyrus (SZDG) using a type II diabetic model. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1 h/day/5 consecutive days at 22 m/min for 5 weeks. Body weight was significantly increased in the control (without running)-ZDF rats compared to that in the other groups. In the control groups blood glucose levels were increased by 392.7 mg/dl in the control-ZDF rats and by 143.3 mg/dl in the control-ZLC rats. However, in the exercise groups, blood glucose levels were similar between the exercise-ZLC and ZDF rats: The blood glucose levels were 110.0 and 118.2 mg/dl, respectively. Ki67 positive nuclei were detected in the SZDG in control and exercise groups. The number of Ki67 positive nuclei was significantly high in exercise groups compared to that in the control groups. In addition, Ki67 positive cells were abundant in ZLC groups compared to those in ZDF groups. DCX-immunoreactive structures in the control-ZDF rats were lower than that in the control-ZLC rats. In the exercise groups, DCX-immunoreactive structures (somata and processes with tertiary dendrites) and DCX protein levels were markedly increased in both the exercise-ZLC and ZDF rats compared to that in the control groups. These results suggest that a treadmill exercise reduces blood glucose levels in ZDF rats and increases cell proliferation and differentiation in the SZDG in ZLC and ZDF rats compared to those in control groups.

Danshen (Radix Salvia miltiorrhizae) has been used as a traditional medicine in Asia for treatment of various microcirculatory disturbance related diseases. Tanshinones are mainly hydrophobic active components, which have been isolated from Danshen and show various biological functions. In this study, we observed the neuroprotective effect of tanshinone I (TsI) against ischemic damage in the gerbil hippocampal CA1 region (CA1) after transient cerebral ischemia and examined its neuroprotective mechanism.The gerbils were divided into vehicle-treated-sham-group, vehicle-treated-ischemia-group, TsI-treated-sham-group, and TsI-treated-ischemia-group. TsI was administrated intraperitoneally three times (once a day for three days) before ischemia-reperfusion. The neuroprotective effect of TsI was examined using HE staining, neuronal nuclei (NeuN) immunohistochemistry and Fluoro-Jade B staining. To investigate the neuroprotective mechanism of TsI after ischemia-reperfusion, immunohistochemical (IHC) and Western blotting analyses for Cu, Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-I (IGF-I) were performed.Treatment with TsI protected pyramidal neurons from ischemia-induced neuronal death in the CA1 after ischemia-reperfusion. In addition, treatment with TsI maintained the levels of SOD1 and SOD2 as determined by IHC and Western blotting in the CA1 after ischemia-reperfusion compared with the vehicle-ischemia-group. In addition, treatment with TsI increased the levels of BDNF and IGF-I determined by IHC and Western blotting in the TsI-treated-sham-group compared with the vehicle-treated-sham-group, and their levels were maintained in the stratum pyramidale of the ischemic CA1 in the TsI-treated-ischemia-group.Treatment with TsI protects pyramidal neurons of the CA1 from ischemic damage induced by transient cerebral ischemia via the maintenance of antioxidants and the increase of neurotrophic factors.

Alpha-synuclein (α-syn) is a presynaptic protein that is richly expressed in the central and peripheral nervous systems of mammals, and it is related to the pathogenesis of Parkinson's disease and other neurodegenerative disorders. In the present study, we compared the distribution of the immunoreactivity of α-syn and its related gliosis in the spinal cord of young adult (2-3 years) and aged (10-12 years) beagle dogs. We discovered that α-syn immunoreactivity was present in many neurons in the thoracic level of the aged spinal cord, however, its protein level was not distinct inform that of the adult spinal cord. In addition, ionized calcium-binding adapter molecule-1 (a marker for microglia) immunoreactivity, and not glial fibrillary acidic protein (a marker for astrocytes) immunoreactivity, was somewhat increased in the aged group compared to the adult group. These results indicate that α-syn immunoreactivity was not dramatically changed in the dog spinal cord during aging.

In this study, we investigated the effects of treadmill exercise on calretinin (CR), a marker of early postmitotic neurons, immunoreactivity in the dentate gyrus (DG) of Zucker diabetic fatty (ZDF) rats, before or after diabetes onset, and Zucker lean control (ZLC) rats. For this study, 6-week-old ZLC and prediabetic ZDF rats, and 22-week-old ZLC and ZDF rats were exercised on the treadmill. Sedentary ZLC and ZDF rats of the same age were used as exercise experiment controls. The exercised prediabetic ZDF rats did not show diabetes onset, while the sedentary prediabetic ZDF rats showed significantly increased blood glucose levels. The exercised diabetic ZDF rats exhibited a decrease in their blood glucose levels compared to the sedentary diabetic ZDF rats, but the levels were still above 20 mmol/l. ZLC rats of both ages were in the normoglycemic range. CR immunoreactivity was detected throughout the DG, including the subgranular zone and the polymorphic layer. Diabetic rats exhibited a significant decrease in the number of CR-immunoreactive cells and fibers in the DG. Exercise in the prediabetic ZDF rats significantly increased the number of CR-immunoreactive cells and fibers in the subgranular zone of the DG. In the ZLC and ZDF rats of chronic diabetic phase, exercise increased CR-immunoreactive neurons in the hilar region. These results suggest that diabetes significantly reduces the number of postmitotic CR-immunoreactive neurons and the intensity of immunoreactivity and that exercise increases these CR-related parameters in a diabetic stage-dependent manner.

Abnormal excess of glucocorticoid is one of feature characteristics in type 2 diabetes. In the present study, we investigated the effect of treadmill exercise at chronic diabetic stages on glucocorticoid receptor (GR) immunoreactivity in the hippocampal CA1 region and dentate gyrus, which are very vulnerable to diabetes. For this study, we used Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats. Twenty-three-week-old ZLC and ZDF rats were put on the treadmill with or without running for 7 weeks and sacrificed at 30 weeks of age. Treadmill exercise significantly decreased diabetes-induced blood glucose and serum corticosteroid levels although they did not drop to control levels. In sedentary ZLC rats, GR immunoreactivity was detected in pyramidal cells of the CA1 region as well as in granule cells of the dentate gyrus. In the sedentary ZDF rats, GR immunoreactivity was significantly increased in these regions. However, treadmill exercise significantly decreased GR immunoreactivity in these regions. These results indicate that treadmill exercise in chronic diabetic rats significantly decreased GR immunoreactivity in the hippocampal CA1 region and dentate gyrus, although blood glucose and serum corticosteroid levels did not fully recover to normal state.