Threshold-like pattern of neuronal activation in the hypothalamus during treadmill running: Establishment of a minimum running stress (MRS) rat model

Soya, Hideaki; Mukai, Akira; Deocaris, Custer C.; Ohiwa, Nao; Chang, Ho‐Wan; Nishijima, Takeshi; Fujikawa, Takahiko; Togashi, Kenji; Saito, Tsuyoshi

doi:10.1016/j.neures.2007.04.004

Cited by 134 publications

(145 citation statements)

References 41 publications

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“…Because exercise can be a physiological stress if exercise intensity exceeds the lactate threshold (44), intense exercise inhibits positive effects of exercise on the hippocampus (33). The previous literature, together with our finding that mild exercise increased hippocampal neuronal activity, leads us to hypothesize that mild intensity of exercise would be preferable to gain benefits of exercise, such as increase in BDNF expression on the hippocampus, although further study is required.…”

Section: Discussionmentioning

confidence: 79%

Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise

Nishijima

Okamoto

Matsui

et al. 2012

Journal of Applied Physiology

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pal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise. J Appl Physiol 112: 197-203, 2012. First published September 22, 2011 doi:10.1152 doi:10. /japplphysiol.00763.2011rent studies have demonstrated that exercise increases regional cerebral blood flow (rCBF), an index of neuronal activity. However, neuronal regulation of the increased rCBF in the brain parenchyma is poorly understood. We developed a running model with rats for monitoring hippocampal cerebral blood flow (Hip-CBF) and found that mild treadmill running increases Hip-CBF in a tetrodotoxin-dependent manner, suggesting that functional hyperemia, an increase in rCBF in response to neuronal activation, occurs in the running rat's hippocampus (Nishijima T and Soya H. Neurosci Res 54: 186-191, 2006). To further support our hypothesis, it was important to discover the neurogenic pathways behind the increase in Hip-CBF that occurred during running. Here, we examine the possible role of N-methyl-D-aspartate (NMDA) receptor/nitric oxide (NO) signaling and group I metabotropic glutamate receptors in mediating the Hip-CBF increase. Hip-CBF during running was measured by laser-Doppler flowmetry. Intrahippocampal drug administration was performed by microdialysis. Mild treadmill running (10 m/min) increased Hip-CBF, which was remarkably attenuated by either NMDA receptor antagonists (1 mM MK-801) or NO synthase inhibitors (2 mM N G -nitro-L-arginine methyl ester). However, group I metabotropic glutamate receptor antagonists {1 mM 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester ϩ 1 mM 2-methyl-6-(phenylethynyl)pyridine hydrochloride} augmented the running-induced Hip-CBF increase. We also found that rCBF in the olfactory bulb was unchanged with running. These results strongly suggest that Hip-CBF during mild exercise is regulated locally under hippocampal neuronal activity, mediated mainly through NMDA receptor/NO signaling. Collectively, these results, together with our previous findings, support our hypothesis that mild exercise elicits neuronal activation, which then triggers functional hyperemia in the rat hippocampus.

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Section: Discussionmentioning

confidence: 79%

Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise

Nishijima

Okamoto

Matsui

et al. 2012

Journal of Applied Physiology

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“…Execise on the treadmill was performed for 1, 3, 7 and 10 days. The experimental procedure for aerobic and anaerobic exercise was adapted from the method of Fahrenia, 2010, 8 which in turn is based on the method of Soya et al 9 All rats were acclimated to the treadmill for 1 week by exposing them to the apparatus moving at low speed.…”

Section: Methodsmentioning

confidence: 99%

Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise

Flora¹,

Freisleben²,

Ferdinal³

et al. 2012

Med J Indones

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Abstrak (156,8 ± 33,1 vs 116,03 ± 5,66) . Begitu pula dengan konsentrasi VEGF pada kelompok anaerobik konsentrasi tertinggi terjadi pada hari pertama (36,37 ± 2,35), sedangkan pada kelompok aerobik konsentrasi VEGF tertinggi terjadi pada hari ke-3 (40,66 ± 1,73). Terdapat korelasi antara konsentrasi HIF-1α dan konsentrasi VEGF jaringan dengan tingkat korelasi sedang (r = 0,59) pada kelompok aerobik dan korelasi yang kuat pada kelompok anaerobik (r = 0,69). Kesimpulan: Aktivitas fisik aerobik dan anaerobik mengakibatkan peningkatan konsentrasi HIF-1α dan VEGF AbstractBackground: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α). The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unlcear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.

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“…We used treadmill running, which can be controlled for speed, and developed a mildintensity treadmill exercise model below the lactate threshold (LT, about 20 m/min) with less blood lactate accumulation and minimal stress response; the LT is a physiologic index of moderate exercise intensity established in rats (25,26) as in humans (27). We have also shown that hippocampal neuronal activity and neurogenesis is induced by the mild-intensity exercise (16,17,28).…”

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confidence: 99%

Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis

Okamoto

Hojo

Inoue

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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128

100

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Mild exercise activates hippocampal neurons through the glutamatergic pathway and also promotes adult hippocampal neurogenesis (AHN). We hypothesized that such exercise could enhance local androgen synthesis and cause AHN because hippocampal steroid synthesis is facilitated by activated neurons via N-methyl-D-aspartate receptors. Here we addressed this question using a mild-intense treadmill running model that has been shown to be a potent AHN stimulator. A mass-spectrometric analysis demonstrated that hippocampal dihydrotestosterone increased significantly, whereas testosterone levels did not increase significantly after 2 wk of treadmill running in both orchidectomized (ORX) and sham castrated (Sham) male rats. Furthermore, analysis of mRNA expression for the two isoforms of 5α-reductases (srd5a1, srd5a2) and for androgen receptor (AR) revealed that both increased in the hippocampus after exercise, even in ORX rats. All rats were injected twice with 5′-bromo-2′deoxyuridine (50 mg/kg body weight, i.p.) on the day before training. Mild exercise significantly increased AHN in both ORX and Sham rats. Moreover, the increase of doublecortin or 5′-bromo-2′deoxyuridine/NeuN-positive cells in ORX rats was blocked by s.c. flutamide, an AR antagonist. It was also found that application of an estrogen receptor antagonist, tamoxifen, did not suppress exercise-induced AHN. These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN via androgenenic mediation.neurosteroid | exercise-induced neurogenesis | low intensity exercise | de novo synthesis | paracrine

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Threshold-like pattern of neuronal activation in the hypothalamus during treadmill running: Establishment of a minimum running stress (MRS) rat model

Cited by 134 publications

References 41 publications

Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise

Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise

Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise

Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis

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