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.
軽度の運動はグルタミン酸経路を介して海馬の神経細胞を活性化し、成人海馬の神経新生（AHN）を促進する。海馬のステロイド合成は、N-methyl-D-aspartate受容体を介して活性化したニューロンによって促進されるため、このような運動は局所的なアンドロゲン合成を促進し、AHNを引き起こす可能性があると我々は仮定している。ここでは、AHNの強力な刺激因子であることが示されている軽度強度のトレッドミルランニングモデルを用いて、この疑問に取り組んだ。睾丸摘出（ORX）および虚勢（Sham）雄ラットにおいて、2週間のトレッドミル走行により、海馬のジヒドロテストステロンが有意に増加したのに対し、テストステロン値は有意な増加を示さなかった。さらに、5αリダクターゼの2つのアイソフォーム（srd5a1、srd5a2）およびアンドロゲン受容体（AR）のmRNA発現を解析したところ、ORXラットでも運動後に海馬で両者が増加することが明らかとなった。すべてのラットにトレーニング前日に5′-bromo-2′deoxyuridine（50 mg/kg body weight, i.p.）を2回注射した。軽度の運動はORXとShamの両ラットでAHNを有意に増加させた。さらに，ORXラットにおけるdoublecortinあるいは5′-bromo-2′deoxyuridine/NeuN陽性細胞の増加は，AR拮抗薬であるフルタミド（s.c.）によって阻害されることが明らかになった．また、エストロゲン受容体拮抗薬であるタモキシフェンの投与は、運動誘発AHNを抑制しないことがわかった。これらの結果は、雄の動物において、軽度の運動は海馬のジヒドロテストステロン合成を促進し、アンドロゲンを介したAHNを増加させるという仮説を支持するものである。
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Someone dies somewhere in the world every 10 seconds owing to physical inactivity – 3.2 million people a year according to the World Health Organisation (WHO). From the age of 50, there is a gradual decline not just in physical activity but also in cognitive abilities since the two are correlated. But which of them influences the other? Does physical activity impact on the brain or is it the other way around? To answer this question, researchers from the University of Geneva (UNIGE), Switzerland, and the NCCR Lives Swiss National Centre of Competence in Research used a database of over 100,000 people aged 50-90 whose physical and cognitive abilities were measured every two years for 12 years. The findings, which are published in the journal Health Psychology, show that – contrary to what was previously thought – cognitive abilities ward off inactivity much more than physical activity prevents the decline in cognitive abilities. All of which means we need to prioritise exercising our brains.
