許多研究發現壓力會導致成年個體之海馬齒狀迴的神經新生數量下降。社會支持已經被證實對壓力有調節的作用，像是實驗室之前的研究發現同種生物的陪伴或是染有同伴氣味的木塊去相陪都能夠有效地回復海馬齒狀迴因壓力所導致的神經新生數量下降之情形，這顯示了同伴的氣味在這樣的調節效果中扮演了重要的角色。在這個研究中我們想要去探討兩個主要的假設。第一點，在同種生物氣味對因壓力而導致神經新生下降之保護作用中是否需要無損之主嗅覺上皮細胞和犁鼻器主導的嗅覺傳導路徑的參與。第二點，不同品種的生物是否也具有像同種生物所具有的對因壓力所導致的神經新生數量下降相似的調節效果。為了驗證第一項假設，老鼠經歷了硫酸鋅鼻腔灌流或是犁鼻器的毀除手術或是兩者皆處理。而在驗證第二項假設的實驗中，我們挑選了五種在親緣關係上跟老鼠不同遠近的動物，大老鼠、倉鼠、天竺鼠、兔子，以及同時作為獵食者關係的狐狸來進行實驗。木塊會浸泡在這些動物使用過的墊料中用夾鍊袋封起來放置60小時。為了強化壓力的效果我們連續使用了隨機時距的電擊和水牢兩種壓力。在壓力給予之前會先在老鼠的腹腔注射一劑Bromodeoxyuridine (BrdU, 100mg/kg)，以標定新生的細胞。老鼠在單獨或是有染著其他種動物氣味的木塊陪伴下連續接受兩種壓力，並且在壓力給完之後放到新的籠子中，並在六個小時之後進行灌流，以便取腦來計算齒狀迴中BrdU和BrdU/DCx所標定的細胞數量。我們的研究發現利用犁鼻器毀除使副嗅覺傳導路徑受損以及用硫酸鋅灌流來破壞主嗅覺傳導路徑並不會影響老鼠在齒狀迴的細胞增生或神經新生。同時，犁鼻器毀除也不會影響同種生物氣味對於因壓力而導致下降的神經新生的保護效果，但硫酸鋅灌流卻會破壞這樣的保護效果。另外，在受壓力時有大老鼠、倉鼠和天竺鼠的氣味陪伴會使得因壓力而導致下降的細胞增生和神經新生回復，而這些氣味本身並不會影響細胞增生或神經新生。兔子氣味的陪伴並不會影響細胞增生或神經新生以及因壓力而導致下降的細胞增生和神經新生。狐狸尿味道的陪伴並不會影響因壓力而導致下降的細胞增生和神經新生，但卻使得細胞增生和神經新生降低。總結以上，我們的研究發現了嗅覺傳導路徑中經由活化主要嗅覺上皮細胞的神經在同伴氣味所產生的對於因壓力而導致下降的細胞增生或神經新生的保護效果中扮演了重要的角色。在會產生氣味的動物品種和老鼠之間親緣關係的遠近導致這些氣味能經由陪伴產生對因壓力而導致下降的細胞增生或神經新生的保護效果。

Many studies have indicated that stress decreases the proliferation of progenitor cells in the dentate gyrus of the hippocampus. Social support, in this regard, has been demonstrated to modulate stress-decreased cell proliferation. For example, our previous study revealed that conspecific’s company or wooden blocks with conspecific odor effectively reversed the stress-decreased neurogenesis in dentate gyrus of hippocampus. Odors derived from conspecifics’ companion play an important role in modulating such an effect. Two hypotheses were examined in this study. First, whether intact main olfactory epithelium (MOE)- and the vomeronasal organ (VNO)-mediated olfactory processing were required for the conspecific odor-exerted protective effect against the stress-decreased neurogenesis. Second, we studied the protective effect of different species’ odors on this stress-decreased neurogenesis. To examine our first hypothesis, some mice were experienced either Zinc Sulfate lavage or Vomeronasal organ removal (VNX) or both. Some mice were underwent sham surgery as control. For investigating our second hypothesis, five species with different phylogenic relationship to mouse pedigree were chosen. Wooden blocks impregnated with conspecific or above-mentioned species’ bedding materials were obtained. In an attempt to maximize the stress effect, shock and restraint stress were combined in a sequence. Bromodeoxyuridine (BrdU, 100mg/kg, one i.p. injection prior to stress treatment) was used to label mitotic cells. Mice experienced combined stress, or along with three wooden blocks impregnated with species-specific odor. Mice were then perfused at six hours after the conclusion of the stress protocol for quantifying the BrdU and BrdU/Dcx positive cells in the dentate gyrus. Our results revealed that the conspecific odor-produced protective effect remained to be intact in mice undergoing VNX. In contrast, the conspecific odor-produced protective effect no longer existed in mice whose MOE was impaired by ZnSO4 lavage. Likewise, the conspecific odor-produced protective effect was not noticed in mice treated with both ZnSO4 lavage and VNX. Moreover, we observed that presence of odors from rats, hamsters, and guinea pigs throughout the stress procedure reversed the stress-decreased cell proliferation and neurogenesis in mouse dentate gyrus, while these odors did not affect mouse dentate cell proliferation or neurogenesis. Presence of rabbits’ odors did not affect mouse dentate cell proliferation, neurogenesis, or the stress-decreased cell proliferation and neurogenesis. Although presence of fox urine odors decreased mouse dentate cell proliferation or neurogenesis, presence of this odor did not affect the stress-decreased cell proliferation or neurogenesis. Taken together, we conclude that olfactory processing via activation of nerons in MOE is responsible for the conspecific odor-produced protective effect against the stress-decreased cell proliferation and neurogenesis. Phylogenetic distances of the odor-generating species and mice contribute to the companions-exerted protective effects against stress-decreased cell proliferation and neurogenesis in mouse dentate gyrus.

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