多年來研究者發現壓力會降低海馬齒狀回 (dentate gyrus, DG)的神經新生成。而在實驗室之前的研究指出在小鼠受到壓力時若有三頭其他小鼠的存在可以有效地防止壓力降低DG中的早期神經新生。進一步的研究更發現甚至近親種族的氣味對於該緩衝壓力的效果可能扮演關鍵的角色。催產素是一種胜肽激素，並被認為與哺乳綱動物的親社會行為和壓力調節有關。最近的研究發現暴露於空氣中催產素可以阻止壓力降低DG中早期神經新生。然而催產素是如何將這種作用經由空氣將其作用傳遞至DG尚不清楚。有趣的是先前的研究發現，暴露於空氣中的催產素並不會很快而明顯的改變血液中催產素的濃度。鼻上皮中含有催產素受體的神經元，我假設該神經元的激活，可能將訊息傳至嗅球，並經由梨狀皮質轉接，最終將刺激訊息傳遞給DG。在這項研究中我使用了 8 周大的 Balb/c 和 C57BL/6 小鼠。為了研究催產素的刺激訊號是否經過前述路徑之一的嗅球，在實驗開始前兩週對小鼠進行了嗅徑切除術。使用 30 分鐘的足部電擊和 30 分鐘的水牢作為複合壓力源。為了測試梨狀皮質是否為催產素傳遞到海馬齒狀回的一個中繼大腦區域，在實驗開始前一周通過顱內注射給小鼠紅藻酸（Kainic acid，簡稱KA）。此外，為了進一步測試在鼻腔中接收到的催產素信號是否通過梨狀皮質，在實驗開始前，對小鼠的前後梨狀皮質進行雙側電燒 (EL) 損傷。通過Nissl染色進行組織學檢查和細胞存活檢查以確保毀除方法是否成功。結果表明，在經過嗅徑切除術後，暴露於空氣中催產素的壓力組的BrdU+和 BrdU+/DCX+細胞數仍低於控制組。這表明嗅徑切除術抑制了催產素的作用，說明催產素的傳導途徑是經嗅球傳入中樞。在 KA 損傷的結果中，所有KA損傷組的BrdU+和 BrdU+/DCX+細胞數均比PBS組較高。但在KA損傷的組別中，KA損傷仍抑制了催產素的效果。在 EL 損傷的結果中，BrdU+ 和 BrdU+/DCX+ 細胞的數量在假手術和 EL 對照之間沒有差異。與 Sham 組相比, EL 組中暴露於催產素的壓力組有降低的趨勢, 但沒有統計學差異。經由這幾個實驗，我展示了催產素經由空氣被動物吸入，該刺激應是從嗅球傳入，並可能在到達海馬體之前穿過梨狀皮質，故能發揮其緩衝壓力對齒狀回神經新生的壓抑作用。

Stress has been found to cause decreases in neurogenesis in hippocampal dentate gyrus (DG). In our previous study, we report that the presence of conspecifics throughout the stress regimen may reliably prevent the stress-induced decreases in DG cell proliferation and early neurogenesis. Furthermore, we find that the encoding of conspecifics’ odors is essential for such conspecifics-related stress-buffering effects. Oxytocin is a peptide hormone and known to associate with mammals’ prosocial behavior and stress modulation. Recently, we notice that airborne oxytocin presentation prevent the stress-induced decreases in DG cell proliferation and early neurogenesis. However, how oxytocin relays such effect to dentate gyrus is not clear. Interestingly, our preliminary study indicates that exposure to oxytocin does not increase the concentration of oxytocin in the blood. Thus, I hypothesized that activation of oxytocin receptor-containing neuron in nasal epithelium may relay the stimulation to DG by way of piriform cortex. In this study, 8-week-old Balb/c and C57BL/6 mice were used. To study whether airborne oxytocin exposure may activate the olfactory signal pathway, olfactory tract transection or sham surgery was performed on mice two weeks before the start of the experiment. Male mice were divided into three groups receiving no stressor, compound stressors and compound stressors with oxytocin exposure. Bromodeoxyuridine (BrdU) was injected intraperitoneally at the beginning of the experiment. Thirty-min foot shock and 30-min restraint in water in combination were employed to serve as compound stressors. Immediately after the conclusion of the compound stressors, the mice were held in separate cages for another 6 hours before returning to their home cage to avoid social interaction confounds. Mice were euthanized three days later, and their brains were removed, cryoprotected and sectioned. BrdU and doublecortin (DCX) were used for immunostaining to label cell proliferation and early neuronal differentiation. To test whether piriform cortex was a relay brain region, mice were received bilateral intracranial kainic acid (KA) injection and electrolytic lesion (EL) in piriform cortex one week before the experiment. Histological examination of cortical lesion was performed by Nissl stain. The results show that the number of BrdU+ cells and BrdU+/DCX+ cells were not affected by olfactory tract transection per se. However, the number of BrdU+/DCX+ cells in the compound stressors and airborne oxytocin group with olfactory tract transection were significantly different from the compound stressors and airborne oxytocin group with the sham surgery. This indicates that the effect of oxytocin is inhibited by olfactory tract transection, which shows that airborne oxytocin signaling pathway may pass through the olfactory bulb. Moreover, the number of BrdU+ cells between mouse group receiving the compound stressors alone and group receiving the compound stressors with airborne oxytocin were comparable. The result of KA lesion experiment showed that the number of BrdU+ cells and BrdU+/DCX+ cells in KA lesion groups were higher than groups. In addition, the number of BrdU+/DCX+ cells in the KA lesion group treated with compound stressors and airborne oxytocin were not different from the KA lesion group treated with compound stressors only. In the EL lesion experiment, the result showed that the number of BrdU+ and BrdU+/DCX+ cells had no difference between the sham and EL control. There was a lowering trend (not statistically significant) that the number of BrdU+ and BrdU+/DCX+ cells were lower in the EL group treated with stress and airborne oxytocin compared to the Sham group treated with stress and oxytocin. In conclusion, this study showed that the effect of airborne oxytocin should start from the olfactory bulb and may pass through the piriform cortex before reaching the hippocampus.

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