Abstract
Recent studies have reported the presence of adult neurogenesis in the arcuate nucleus periventricular space (pvARH) and in the median eminence (ME), two structures involved in reproductive function. In sheep, a seasonal mammal, decreasing daylight in autumn induces a higher neurogenic activity in these two structures. However, the different types of neural stem and progenitor cells (NSCs/NPCs) that populate the arcuate nucleus and median eminence, as well as their location, have not been evaluated. Here, using semi-automatic image analyzing processes, we identified and quantified the different populations of NSCs/NPCs, showing that, during short days, higher densities of [SOX2 +] cells are found in pvARH and ME. In the pvARH, higher densities of astrocytic and oligodendrocitic progenitors mainly contribute to these variations. The different populations of NSCs/NPCs were mapped according to their position relative to the third ventricle and their proximity to the vasculature. We showed that [SOX2 +] cells extended deeper into the hypothalamic parenchyma during short days. Similarly, [SOX2 +] cells were found further from the vasculature in the pvARH and the ME, at this time of year, indicating the existence of migratory signals. The expression levels of neuregulin transcripts (NRGs), whose proteins are known to stimulate proliferation and adult neurogenesis and to regulate progenitor migration, as well as the expression levels of ERBB mRNAs, cognate receptors for NRGs, were assessed. We showed that mRNA expression changed seasonally in pvARH and ME, suggesting that the ErbB-NRG system is potentially involved in the photoperiodic regulation of neurogenesis in seasonal adult mammals.
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Abbreviations
- ARH:
-
Arcuate nucleus
- LP:
-
Long photoperiod
- MBH:
-
Mediobasal hypothalamus
- ME:
-
Median eminence
- NRGs:
-
Neuregulins
- NSCs/NPCs:
-
Neural stem and progenitor cells
- NSCs:
-
Neural stem cells
- pvARH:
-
Periventricular space of the arcuate nucleus
- [SOX2-HuC/D +]:
-
Cells immunonegative for SOX2 and immunopositive for HuC/D
- [SOX2-Olig2 +]:
-
Cells immunonegative for SOX2 and immunopositive for Olig2
- [SOX2 +] cells:
-
Neural stem and progenitor cells expressing SOX2
- [SOX2 + HuC/D +]:
-
SOX2 + population densities that co-express HuC/D identifying neuron progenitor cells
- [SOX2 + Olig2 +]:
-
SOX2 + population densities that co-express Olig2 identifying neoligodendrocyte progenitor cells
- [SOX2 + S100 +]:
-
SOX2 + population densities that co-express S100 identifying astrocyte progenitor cells
- [SOX2-S100 +]:
-
Cells immunonegative for SOX2 and immunopositive for S100
- SGZ:
-
Subgranular zone of the hippocampal dentate gyrus
- SP:
-
Short photoperiod
- SVZ:
-
Subventricular zone of the lateral ventricles
References
Andréoletti O, Berthon P, Levavasseur E, Marc D, Lantier F, Monks E, Elsen J-M, Schelcher F (2002) Phenotyping of protein-prion (PrPsc)-accumulating cells in lymphoid and neural tissues of naturally scrapie-affected sheep by double-labeling immunohistochemistry. J Histochem Cytochem 50:1357–1370. https://doi.org/10.1177/002215540205001009
Anton ES, Marchionni MA, Lee KF, Rakic P (1997) Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex. Development 124:3501–3510. https://doi.org/10.1242/dev.124.18.3501
Bartkowska K, Djavadian RL, Taylor JRE, Turlejski K (2008) Generation recruitment and death of brain cells throughout the life cycle of Sorex shrews (Lipotyphla). Eur J Neurosci 27:1710–1721. https://doi.org/10.1111/j.1460-9568.2008.06133.x
Batailler M, Chesneau D, Derouet L, Butruille L, Segura S, Cognié J, Dupont J, Pillon D, Migaud M (2018) Pineal-dependent increase of hypothalamic neurogenesis contributes to the timing of seasonal reproduction in sheep. Sci Rep 8:6188. https://doi.org/10.1038/s41598-018-24381-4
Batailler M, Droguerre M, Baroncini M, Fontaine C, Prevot V, Migaud M (2014) DCX-expressing cells in the vicinity of the hypothalamic neurogenic niche: a comparative study between mouse, sheep, and human tissues. J Comp Neurol 522:1966–1985. https://doi.org/10.1002/cne.23514
Buonanno A, Fischbach GD (2001) Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 11:287–296. https://doi.org/10.1016/S0959-4388(00)00210-5
Burger DK, Saucier JM, Iwaniuk AN, Saucier DM (2013) Seasonal and sex differences in the hippocampus of a wild rodent. Behav Brain Res 236:131–138. https://doi.org/10.1016/j.bbr.2012.08.044
Butruille L, Batailler M, Mazur D, Prévot V, Migaud M (2018) Seasonal reorganization of hypothalamic neurogenic niche in adult sheep. Brain Struct Funct 223:91–109. https://doi.org/10.1007/s00429-017-1478-z
Butruille L, Batailler M, Cateau ML, Sharif A, Leysen V, Prévot V, Vaudin P, Pillon D, Migaud M (2022) Selective depletion of adult GFAP-expressing tanycytes leads to hypogonadotropic hypogonadism in males. Front Endocrinol (Lausanne) 13:869019. https://doi.org/10.3389/fendo.2022.869019
Chevillard P-M, Batailler M, Piégu B, Estienne A, Blache M-C, Dubois J-P, Pillon D, Vaudin P, Dupont J, Just N, Migaud M (2022) Seasonal vascular plasticity in the mediobasal hypothalamus of the adult ewe. Histochem Cell Biol. https://doi.org/10.1007/s00418-022-02079-z
Dardente H, Migaud M (2021) Thyroid hormone and hypothalamic stem cells in seasonal functions. Vitam Horm 116:91–131. https://doi.org/10.1016/bs.vh.2021.02.005
Episkopou V (2005) SOX2 functions in adult neural stem cells. Trends Neurosci 28:219–221. https://doi.org/10.1016/j.tins.2005.03.003
Galea LAM, McEwen BS (1999) Sex and seasonal changes in the rate of cell proliferation in the dentate gyrus of adult wild meadow voles. Neuroscience 89:955–964. https://doi.org/10.1016/S0306-4522(98)00345-5
Ghashghaei HT, Weber J, Pevny L, Schmid R, Schwab MH, Lloyd KCK, Eisenstat DD, Lai C, Anton ES (2006) The role of neuregulin–ErbB4 interactions on the proliferation and organization of cells in the subventricular zone. Proc Natl Acad Sci USA 103:1930–1935. https://doi.org/10.1073/pnas.0510410103
Gussenhoven R, Ophelders DRMG, Kemp MW, Payne MS, Spiller OB, Beeton ML, Stock SJ, Cillero-Pastor B, Barré FPY, Heeren RMA, Kessels L, Stevens B, Rutten BP, Kallapur SG, Jobe AH, Kramer BW, Wolfs TGAM (2017) The paradoxical effects of chronic intra-amniotic ureaplasma parvum exposure on ovine fetal brain development. Dev Neurosci 39:472–486. https://doi.org/10.1159/000479021
Helfer G, Barrett P, Morgan PJ (2019) A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals. J Neuroendocrinol 31(3):e12680. https://doi.org/10.1111/jne.12680
Homem CC, Repic M, Knoblich JA (2015) Proliferation control in neural stem and progenitor cells. Nat Rev Neurosci 16:647–659. https://doi.org/10.1038/nrn4021
Huang L, DeVries GJ, Bittman EL (1998) Photoperiod regulates neuronal bromodeoxyuridine labeling in the brain of a seasonally breeding mammal. J Neurobiol 36:410–420. https://doi.org/10.1002/(sici)1097-4695(19980905)36:3%3c410::aid-neu8%3e3.0.co;2-z
Ibrahim D, Nakamuta N (2018) Comparative histochemical analysis of glycoconjugates in the nasal vestibule of camel and sheep. Microsc Res Tech 81:681–689. https://doi.org/10.1002/jemt.23024
Jones JT, Ballinger MD, Pisacane PI, Lofgren JA, Fitzpatrick VD, Fairbrother WJ, Wells JA, Sliwkowski MX (1998) Binding interaction of the Heregulinβ egf domain with ErbB3 and ErbB4 receptors assessed by alanine scanning mutagenesis. J Biol Chem 273:11667–11674. https://doi.org/10.1074/jbc.273.19.11667
Karakatsani A, Shah B, Ruiz de Almodovar C (2019) Blood vessels as regulators of neural stem cell properties. Front Mol Neurosci 12:85. https://doi.org/10.3389/fnmol.2019.00085
Kokoeva MV, Yin H, Flier JS (2005) Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 310:679–683. https://doi.org/10.1126/science.1115360
Kuhn HG, Toda T, Gage FH (2018) Adult hippocampal neurogenesis: a coming-of-age story. J Neurosci 38:10401–10410. https://doi.org/10.1523/JNEUROSCI.2144-18.2018
Ledonne A, Mercuri NB (2019) On the modulatory roles of neuregulins/ErbB signaling on synaptic plasticity. Int J Mol Sci 21:275. https://doi.org/10.3390/ijms21010275
Lévy F, Batailler M, Meurisse M, Migaud M (2017) Adult neurogenesis in sheep: characterization and contribution to reproduction and behavior. Front Neurosci 11:570. https://doi.org/10.3389/fnins.2017.00570
Lim DA, Tramontin AD, Trevejo JM, Herrera DG, García-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28:713–726. https://doi.org/10.1016/s0896-6273(00)00148-3
Liu F-F, Stone JR, Schuldt AJT, Okoshi K, Okoshi MP, Nakayama M, Ho KKL, Manning WJ, Marchionni MA, Lorell BH, Morgan JP, Yan X (2005) Heterozygous knockout of neuregulin-1 gene in mice exacerbates doxorubicin-induced heart failure. Am J Physiol Heart Circ Physiol 289:H660-666. https://doi.org/10.1152/ajpheart.00268.2005
Louhivuori LM, Turunen PM, Louhivuori V, Yellapragada V, Nordström T, Uhlén P, Åkerman KE (2018) Regulation of radial glial process growth by glutamate via mGluR5/TRPC3 and neuregulin/ErbB4. Glia 66:94–107. https://doi.org/10.1002/glia.23230
Mahar I, MacIsaac A, Kim JJ, Qiang C, Davoli MA, Turecki G, Mechawar N (2016) Effects of neuregulin-1 administration on neurogenesis in the adult mouse hippocampus, and characterization of immature neurons along the septotemporal axis. Sci Rep 6:30467. https://doi.org/10.1038/srep30467
Mei L, Nave K-A (2014) Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron 83:27–49. https://doi.org/10.1016/j.neuron.2014.06.007
Mei L, Xiong W-C (2008) Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 9:437–452. https://doi.org/10.1038/nrn2392
Migaud M, Batailler M, Pillon D, Franceschini I, Malpaux B (2011) Seasonal changes in cell proliferation in the adult sheep brain and pars tuberalis. J Biol Rhythms 26:486–496. https://doi.org/10.1177/0748730411420062
Migaud M, Butrille L, Batailler M (2015) Seasonal regulation of structural plasticity and neurogenesis in the adult mammalian brain: focus on the sheep hypothalamus. Front Neuroendocrinol 37:146–157. https://doi.org/10.1016/j.yfrne.2014.11.004
Migaud M, Butruille L, Duittoz A, Pillon D, Batailler M (2016) Adult neurogenesis and reproductive functions in mammals. Theriogenology 86(1):313–323. https://doi.org/10.1016/j.theriogenology.2016.04.044
Mirzadeh Z, Doetsch F, Sawamoto K, Wichterle H, Alvarez-Buylla A (2010) The subventricular zone en-face: wholemount staining and ependymal flow. J Vis Exp 1938. https://doi.org/10.3791/1938
Mirzadeh Z, Kusne Y, Duran-Moreno M, Cabrales E, Gil-Perotin S, Ortiz C, Chen B, Garcia-Verdugo JM, Sanai N, Alvarez-Buylla A (2017) Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories. Nat Commun 8:13759. https://doi.org/10.1038/ncomms13759
Obernier K, Alvarez-Buylla A (2019) Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development 146:dev156059. https://doi.org/10.1242/dev.156059
Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, Adams RH, Parrinello S (2014) Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol 16:1045–1056. https://doi.org/10.1038/ncb3045
Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494. https://doi.org/10.1002/1096-9861(20001002)425:4%3c479::aid-cne2%3e3.0.co;2-3
Pellegrino G, Trubert C, Terrien J, Pifferi F, Leroy D, Loyens A, Migaud M, Baroncini M, Maurage C-A, Fontaine C, Prévot V, Sharif A (2018) A comparative study of the neural stem cell niche in the adult hypothalamus of human, mouse, rat and gray mouse lemur (Microcebus murinus). J Comp Neurol 526:1419–1443. https://doi.org/10.1002/cne.24376
Rio C, Rieff HI, Qi P, Corfas G (1997) Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron 19:39–50. https://doi.org/10.1016/S0896-6273(00)80346-3
Robins SC, Stewart I, McNay DE, Taylor V, Giachino C, Goetz M, Ninkovic J, Briancon N, Maratos-Flier E, Flier JS, Kokoeva MV, Placzek M (2013) α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4:2049. https://doi.org/10.1038/ncomms3049
Sato T, Sato F, Kamezaki A, Sakaguchi K, Tanigome R, Kawakami K, Sehara-Fujisawa A (2015) Neuregulin 1 type II-ErbB signaling promotes cell divisions generating neurons from neural progenitor cells in the developing zebrafish brain. PLoS One 10:e0127360. https://doi.org/10.1371/journal.pone.0127360
Sharif A, Duhem-Tonnelle V, Allet C, Baroncini M, Loyens A, Kerr-Conte J, Collier F, Blond S, Ojeda SR, Junier M-P, Prevot V (2009) Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain. Glia 57:362–379. https://doi.org/10.1002/glia.20762
Sharif A, Prevot V (2010) ErbB receptor signaling in astrocytes: a mediator of neuron-glia communication in the mature central nervous system. Neurochemistry International, Glia as Neurotransmitter Sources and Sensors 57:344–358. https://doi.org/10.1016/j.neuint.2010.05.012
Shearer KD, Stoney PN, Nanescu SE, Helfer G, Barrett P, Ross AW, Morgan PJ, McCaffery P (2012) Photoperiodic expression of two RALDH enzymes and the regulation of cell proliferation by retinoic acid in the rat hypothalamus. J Neurochem 122(4):789–799. https://doi.org/10.1111/j.1471-4159.2012.07824.x
Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N, Vincent P, Pumiglia K, Temple S (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304:1338–1340. https://doi.org/10.1126/science.1095505
Shen Q, Wang Y, Kokovay E, Lin G, Chuang S-M, Goderie SK, Roysam B, Temple S (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3:289–300. https://doi.org/10.1016/j.stem.2008.07.026
Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288. https://doi.org/10.1016/j.stem.2008.07.025
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(research0034):1. https://doi.org/10.1186/gb-2002-3-7-research0034
Walton JC, Pyter LM, Weil ZM, Nelson RJ (2012) Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus). PLoS One 7:e42743. https://doi.org/10.1371/journal.pone.0042743
Yan L, Shamir A, Skirzewski M, Leiva-Salcedo E, Kwon OB, Karavanova I, Paredes D, Malkesman O, Bailey KR, Vullhorst D, Crawley JN, Buonanno A (2018) Neuregulin-2 ablation results in dopamine dysregulation and severe behavioral phenotypes relevant to psychiatric disorders. Mol Psychiatry 23:1233–1243. https://doi.org/10.1038/mp.2017.22
Yoo S, Blackshaw S (2018) Regulation and function of neurogenesis in the adult mammalian hypothalamus. Prog Neurobiol 170:53–66. https://doi.org/10.1016/j.pneurobio.2018.04.001
Zhang D, Sliwkowski MX, Mark M, Frantz G, Akita R, Sun Y, Hillan K, Crowley C, Brush J, Godowski PJ (1997) Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4. Proc Natl Acad Sci USA 94:9562–9567. https://doi.org/10.1073/pnas.94.18.9562
Zhou X, Zhong S, Peng H, Liu J, Ding W, Sun L, Ma Q, Liu Z, Chen R, Wu Q, Wang X (2020) Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus. Nat Commun 11:4063. https://doi.org/10.1038/s41467-020-17890-2
Zilkha-Falb R, Kaushansky N, Ben-Nun A (2020) The median eminence, a new oligodendrogenic niche in the adult mouse brain. Stem Cell Rep 14:1076–1092. https://doi.org/10.1016/j.stemcr.2020.04.005
Acknowledgements
The authors thank the PAO experimental unit No. 1297 (EU0028; INRAE Val de Loire) for taking care of the animals.
Funding
This work was funded by the Agence Nationale de la Recherche ANR-16-CE37-0006 (to Martine Migaud). Pierre-Marie Chevillard received a grant from The Ministry of Higher Education, Research and Innovation (MESRI).
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This article does not contain any studies with human participants. Animals were handled and cared for in accordance with the EC Directive of 24 November 1986 (86/609/EEC) and with authorization A37110 from the French Ministry of Agriculture. All procedures were approved by the Regional Ethics Committee (Comité Régional d’Ethique pour l’Expérimentation Animale, Centre-Limousin region (CREEA)).
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Chevillard, PM., Batailler, M., Dubois, JP. et al. Seasonal remodeling of the progenitor pool and its distribution in the ewe mediobasal hypothalamus. Cell Tissue Res 392, 745–761 (2023). https://doi.org/10.1007/s00441-023-03745-x
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DOI: https://doi.org/10.1007/s00441-023-03745-x