目前已知在成年哺乳類動物大腦內有神經幹細胞存在。其中一處位於側腦室旁的側腦室下區（subventricular zone）。此處的神經幹細胞分化為神經母細胞後會往嗅球遷移，並分化成中間神經元（interneuron）。此過程稱為神經元新生，並由細胞增生、遷移、分化及細胞存活四個過程所組成。嗅球按其結構可以分成主嗅球與副嗅球兩大部分，分別掌管環境中氣味因子及費洛蒙的訊息傳遞。根據日前研究顯示，雄性小鼠的費洛蒙可以刺激雌鼠副嗅球內的神經元新生，而且也會對懷孕的雌鼠造成布魯斯效應（Bruce effect）¬－懷孕早期的雌鼠暴露於非交配雄鼠的費洛蒙氣味下，所造成的流產情形。雖然目前已知費洛蒙會對神經元新生造成影響，但對於它們是否會影響新細胞的增生、分化或存活則還不清楚。此外，目前也還不清楚是否雌鼠副嗅球內的神經元新生對於費洛蒙記憶形成的重要性。因此，本實驗主要想探討雄性費洛蒙對於雌鼠副嗅球內之神經元新生所造成的影響。根據實驗結果，我們發現雄性費洛蒙可以促進側腦室下區的細胞增生及副嗅球內新細胞的存活，但對於副嗅球內的神經元分化則沒有影響。當有費洛蒙記憶的雌鼠暴露於含有另一雄性費洛蒙環境下時，會降低副嗅球內新細胞的存活率。而此由費洛蒙誘導之神經元新生，可能需經由正腎上腺素調控。由以上結果可知，雄性費洛蒙對雌鼠副嗅球內之神經元新生具有相當重要的角色。

It has been known that stem cells exist in two areas of adult mammalian brains. One of these is the subventricular zone along the lateral ventricle. These stem cells give rise to neuroblasts and differentiate into olfactory bulb interneurons which play important roles in odor discrimination. This process is called neurogenesis and is composed by four aspects: proliferation, migration, differentiation and survival. The olfactory bulb consists of two functionally distinct parts, the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which detect environmental odorants and pheromones, respectively. Previous studies have shown that male pheromones could stimulate neurogensis in the female AOB. Also, it could cause Bruce effect, the male-induced pregnancy block when the pregnant female is exposed to pheromones of a new male. Although the roles of pheromones in adult neurogenesis are emerging, whether they affect cell proliferation, neuronal differentiation or survival remain elusive. It is also unclear whether adult neurogenesis in the AOB is required for the formation of pheromonal memory in female mice. Therefore, the aim of this work is to study the effects of male pheromones on different aspects of AOB neurogenesis in female mice. We found that male pheromones could promote cell proliferation in SVZ and new cell survival but not neuronal differentiation of newborn cells in AOB. Moreover, survival of newborn cells was decreased when females were exposed to pheromones from a second male. Also, pheromone-induced AOB neurogenesis may be regulated by norepinephrine. In conclusion, male pheromones play important roles in adult AOB neurogenesis of female mice.

Adachi K, Mirzadeh Z, Sakaguchi M, Yamashita T, Nikolcheva T, Gotoh Y, Peltz G, Gong L, Kawase T, Alvarez-Buylla A, Okano H, Sawamoto K (2007) Beta-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. Stem Cells 25:2827-2836.
Alonso M, Viollet C, Gabellec MM, Meas-Yedid V, Olivo-Marin JC, Lledo PM (2006) Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb. J Neurosci 26:10508-10513.
Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963-970.
Bolteus AJ, Bordey A (2004) GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone. J Neurosci 24:7623-7631.
Brennan PA, Keverne EB (1997) Neural mechanisms of mammalian olfactory learning. Prog Neurobiol 51:457-481.
Conover JC, Doetsch F, Garcia-Verdugo JM, Gale NW, Yancopoulos GD, Alvarez-Buylla A (2000) Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat Neurosci 3:1091-1097.
Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, van der Kooy D (1996) In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain. J Neurosci 16:2649-2658.
Fan S, Luo M (2009) The organization of feedback projections in a pathway important for processing pheromonal signals. Neuroscience 161:489-500.
Feierstein CE, Lazarini F, Wagner S, Gabellec MM, de Chaumont F, Olivo-Marin JC, Boussin FD, Lledo PM, Gheusi G (2010) Disruption of Adult Neurogenesis in the Olfactory Bulb Affects Social Interaction but not Maternal Behavior. Front Behav Neurosci 4:176.
Giachino C, De Marchis S, Giampietro C, Parlato R, Perroteau I, Schutz G, Fasolo A, Peretto P (2005) cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb. J Neurosci 25:10105-10118.
Goldman SA, Nottebohm F (1983) Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci U S A 80:2390-2394.
Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2:260-265.
Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A 95:3168-3171.
Hack I, Bancila M, Loulier K, Carroll P, Cremer H (2002) Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis. Nat Neurosci 5:939-945.
Jacques TS, Relvas JB, Nishimura S, Pytela R, Edwards GM, Streuli CH, ffrench-Constant C (1998) Neural precursor cell chain migration and division are regulated through different beta1 integrins. Development 125:3167-3177.
Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493-495.
Larsen CM, Kokay IC, Grattan DR (2008) Male pheromones initiate prolactin-induced neurogenesis and advance maternal behavior in female mice. Horm Behav 53:509-517.
Lazarini F, Lledo PM (2011) Is adult neurogenesis essential for olfaction? Trends Neurosci 34:20-30.
Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28:713-726.
Linnarsson S, Willson CA, Ernfors P (2000) Cell death in regenerating populations of neurons in BDNF mutant mice. Brain Res Mol Brain Res 75:61-69.
Liu SY, Zhang ZY, Song YC, Qiu KJ, Zhang KC, An N, Zhou Z, Cai WQ, Yang H (2004) SVZa neural stem cells differentiate into distinct lineages in response to BMP4. Exp Neurol 190:109-121.
Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179-193.
Lledo PM, Saghatelyan A (2005) Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions, and the effects of sensory experience. Trends Neurosci 28:248-254.
Mak GK, Enwere EK, Gregg C, Pakarainen T, Poutanen M, Huhtaniemi I, Weiss S (2007) Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat Neurosci 10:1003-1011.
Mak GK, Weiss S (2010) Paternal recognition of adult offspring mediated by newly generated CNS neurons. Nat Neurosci 13:753-758.
Ng KL, Li JD, Cheng MY, Leslie FM, Lee AG, Zhou QY (2005) Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science 308:1923-1927.
Oboti L, Savalli G, Giachino C, De Marchis S, Panzica GC, Fasolo A, Peretto P (2009) Integration and sensory experience-dependent survival of newly-generated neurons in the accessory olfactory bulb of female mice. Eur J Neurosci 29:679-692.
Ono K, Tomasiewicz H, Magnuson T, Rutishauser U (1994) N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 13:595-609.
Palma V, Lim DA, Dahmane N, Sanchez P, Brionne TC, Herzberg CD, Gitton Y, Carleton A, Alvarez-Buylla A, Ruiz i Altaba A (2005) Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 132:335-344.
Platel JC, Dave KA, Bordey A (2008) Control of neuroblast production and migration by converging GABA and glutamate signals in the postnatal forebrain. J Physiol 586:3739-3743.
Platel JC, Dave KA, Gordon V, Lacar B, Rubio ME, Bordey A (2010) NMDA receptors activated by subventricular zone astrocytic glutamate are critical for neuroblast survival prior to entering a synaptic network. Neuron 65:859-872.
Rochefort C, Gheusi G, Vincent JD, Lledo PM (2002) Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory. J Neurosci 22:2679-2689.
Rosser AE, Keverne EB (1985) The importance of central noradrenergic neurones in the formation of an olfactory memory in the prevention of pregnancy block. Neuroscience 15:1141-1147.
Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S (2003) Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science 299:117-120.
Thompson RN, McMillon R, Napier A, Wekesa KS (2007) Pregnancy block by MHC class I peptides is mediated via the production of inositol 1,4,5-trisphosphate in the mouse vomeronasal organ. J Exp Biol 210:1406-1412.
Tropepe V, Craig CG, Morshead CM, van der Kooy D (1997) Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci 17:7850-7859.
van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266-270.
Veyrac A, Didier A, Colpaert F, Jourdan F, Marien M (2005) Activation of noradrenergic transmission by alpha2-adrenoceptor antagonists counteracts deafferentation-induced neuronal death and cell proliferation in the adult mouse olfactory bulb. Exp Neurol 194:444-456.
Veyrac A, Sacquet J, Nguyen V, Marien M, Jourdan F, Didier A (2009) Novelty determines the effects of olfactory enrichment on memory and neurogenesis through noradrenergic mechanisms. Neuropsychopharmacology 34:786-795.
Walker MR, Patel KK, Stappenbeck TS (2009) The stem cell niche. J Pathol 217:169-180.
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645-660.