Abstract
The hilus plays an important role modulating the excitability of the hippocampal dentate gyrus (DG). It also harbors proliferative cells whose proliferation rate is modified during pathological events. However, the characterization of these cells, in terms of cellular identity, lineage, and fate, as well as the morphology and proportion of each cell subpopulation has been poorly studied. Therefore, a deeper investigation of hilar proliferative cells might expand the knowledge not only in the physiology, but in the pathophysiological processes related to the hippocampus too. The aim of this work was to perform an integrative study characterizing the identity of proliferative cells populations harbored in the hilus, along with morphology and proportion. In addition, this study provides comparative evidence of the subgranular zone (SGZ) of the DG. Quantified cells included proliferative, neural precursor, Type 1, oligodendrocyte progenitor (OPCs), neural progenitor (NPCs), and proliferative mature astrocytes in the hilus and SGZ of Wistar adult rats. Our results showed that 84% of the hilar proliferative cells correspond to neural precursor cells, OPCs and NPCs being the most abundant at 54 and 45%, respectively, unlike the SGZ, where OPCs represent only 11%. Proliferative mature astrocytes and Type 1-like cells were rarely observed in the hilus. Together, our results lay the basis for future studies focused on the lineage and fate of hilar proliferative cells and suggest that the hilus could be relevant to the formation of new cells that modulate multiple physiological processes governed by the hippocampus.
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modified from Paxinos and Watson (1986)]. Right: photomicrograph of the dentate gyrus evidencing the limits between granular layer, SGZ, and hilus. SGZ was defined as the area occupied by two cell bodies, toward up and down (white dotted lines) from the inferior edge (yellow dotted line) of the granular layer. SGZ subgranular zone, CA3 field CA3 of Ammon’s horn. (Color figure online)
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References
Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94:991–1026. https://doi.org/10.1152/physrev.00004.2014
Altman J (1963) Autoradiographic investigation of cell in the brains of rats and cats. Anat Rec 145:573–591
Amaral DG, Scharfman HE, Lavenex P (2007) The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog Brain Res 163:3–22
Arnold K, Sarkar A, Yram MA, Polo JM, Bronson R, Sengupta S, Seandel M, Geijsen N, Hochedlinger K (2011) Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell 9:317–329. https://doi.org/10.1016/j.stem.2011.09.001
Berg DA, Bond AM, Ming G, Song H (2018) Radial glial cells in the adult dentate gyrus: what are they and where do they come from? F1000Res 7:277. https://doi.org/10.12688/f1000research.12684.1
Bermudez-Hernandez K, Lu YL, Moretto J, Jain S, LaFrancois JJ, Duffy AM, Scharfman HE (2017) Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX. Brain Struct Funct 222:3147–3161. https://doi.org/10.1007/s00429-017-1391-5
Boneva NB, Kaplamadzhiev DB, Sahara S, Kikuchi H, Pyko IV, Kikuchi M, Tonchev AB, Yamashima T (2011) Expression of fatty acid-binding proteins in adult hippocampal neurogenic niche of postischemic monkeys. Hippocampus 21:162–171. https://doi.org/10.1002/hipo.20732
Bonfanti L, Nacher J (2012) New scenarios for neuronal structural plasticity in non-neurogenic brain parenchyma: the case of cortical layer II immature neurons. Prog Neurobiol 98:1–15. https://doi.org/10.1016/j.pneurobio.2012.05.002
Brown JP, Couillard-Després S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10
Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344
Cooper-Kuhn CM, Kuhn HG (2002) Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Brain Res Dev Brain Res 134:13–21
Danielson NB, Turi GF, Ladow M, Chavlis S, Petrantonakis PC, Poirazi P, Losonczy A (2017) In vivo imaging of dentate gyrus mossy cells in behaving mice. Neuron 93:552–559. https://doi.org/10.1016/j.neuron.2016.12.019
Encinas JM, Michurina TV, Peunova N, Park JH, Tordo J, Peterson DA, Fishell G, Koulakov A, Enikolopov G (2011) Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8:566–579. https://doi.org/10.1016/j.stem.2011.03.010
Ferri AL, Cavallaro M, Braida D, DiCristofano A, Canta A, Vezzani A, Ottolenghi S, Pandolfi PP, Sala M, DeBiasi S, Nicolis SK (2004) Sox2 deficency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131:3805–3819
Filippov V, Kronenberg G, Pivneva T, Reuter K, Steiner B, Wang LP, Yamaguchi M, Kettenmann H, Kempermann G (2003) Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci 23:373–382
Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438
Ge WP, Miyawaki A, Gage FH, Jan YN, Jan LY (2012) Local generation of glia is a major astrocyte source in postnatal cortex. Nature 484:376–380. https://doi.org/10.1038/nature10959
Gould E, Tanapat P (1997) Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult rat. Neuroscience 80:427–436
Gould E, Cameron HA, Daniels DC, Wooley CS, McEwen BS (1992) Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci 12:3642–3650
Houser CR (2007) Interneurons of the dentate gyrus: an overview of cell types, terminal field and neurochemical identity. Prog Brain Res 163:217–232. https://doi.org/10.1016/S0079-6123(07)63013-1
Huang W, Zhao N, Bai X, Karram K, Trotter J, Goebbels S, Scheller A, Kirchhoff F (2014) Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2glia during development. Glia 62:896–913. https://doi.org/10.1002/glia.22648
Jessberger S, Toni N, Clemenson GD Jr, Ray J, Gage FH (2008) Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nat Neurosci 11:888–893. https://doi.org/10.1038/nn.2148
Jinde S, Zsiros V, Nakazawa K (2013) Hilar mossy cell circuitry controlling dentate granule cell excitability. Front Neural Circuits 7:14. https://doi.org/10.3389/fncir.2013.00014
Kang SH, Fukaya M, Yang JK, Rothstein JD, Bergles DE (2010) NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron 68:668–681. https://doi.org/10.1016/j.neuron.2010.09.009
Kapfhammer JP, Schwab ME (1992) Modulators of neuronal migration and neurite growth. Curr Opin Cell Biol 4:863–868
Klempin F, Kronenberg G, Cheung G, Kettenmann H, Kempermann G (2011) Properties of doublecortin-(DCX)-expressing. PLoS ONE 6:e25760. https://doi.org/10.1371/journal.pone.0025760
Kochman LJ, Formal CA, Jacobs BL (2009) Suppression of hippocampal cells proliferation by short-term stimulant drug administration in adult rat. Eur J Neursoci 29:2157–2165. https://doi.org/10.1111/j.1460-9568.2009.06759.x
Komitova M, Eriksson PS (2004) Sox-2 is expressed by neural progenitor and astroglia in the adult rat brain. Neurosci Lett 369:24–27
Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463
Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033
Leiter O, Kempermann G, Walker TL (2016) A common language: how neuroimmunological cross talk regulates adult hippocampal neurogenesis. Stem Cells Int 2016:1681590. https://doi.org/10.1155/2016/1681590
Leung L, Andrews-Zwilling Y, Yoon SY, Jain S, Ring K, Dai J, Wang MM, Tong L, Walker D, Huang Y (2012) Apolipoprotein E4 cause age- and sex-dependent impairments of hilar GABAergic interneurons and learning and memory deficits in mice. PLoS ONE 7:e53569. https://doi.org/10.1371/journal.pone.0053569
López-Juárez A, Remaud S, Hassani Z, Jolivet P, Pierre Simons J, Sontag T, Yoshikawa K, Price J, Morvan-Dubois G, Demeneix BA (2012) Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche. Cell Stem Cell 10:531–543. https://doi.org/10.1016/j.stem.2012.04.008
Lübke J, Frotscher M, Spruston N (1998) Specialized electrophysiological properties of anatomically identified neurons in the hilar region of the rat fascia dentata. J Neurophysiol 79:1518–1534
Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Götz M, Haas CA, Kempermann G, Taylor V, Gianchino C (2010) Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6:445–456
Mannari T, Sawa H, Furube E, Fukushima S, Nishikawa K, Nakashimna T, Miyata S (2014) Antidepressant-induced vascular dynamics in the hippocampus of adult mouse brain. Cell Tissue Res 358:43–55. https://doi.org/10.1007/s00441-014-1933-6
Myers CE, Bermudez-Hernandez K, Scharfman HE (2013) The influence of ectopic migration of granule cells into the hilus on dentate gyrus-CA3 function. PLoS ONE 8:e68208. https://doi.org/10.1371/journal.pone.0068208
Nacher J, Crespo C, McEwen BS (2001) Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14:629–644
Namba T, Mochizuki H, Onodera M, Mizuno Y, Namiki H, Seki T (2005) The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatalrat dentate gyrus. Eur J Neurosci 22:1928–1941
Olariu A, Cleaver KM, Cameron HA (2007) Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle. J Comp Neurol 501:659–667
Overall RW, Walker TL, Fischer T, Bradt MD, Kempermann G (2016) Different mechanisms must be considered to explain the increase hippocampal neural precursor cell proliferation by physical activity. Front Neurosci 10:362. https://doi.org/10.3389/fnins.2016.00362
Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494
Patro N, Naik A, Patro IK (2015) Differential temporal expression of S100β in developing rat brain. Front Cell Neurosci 9:87. https://doi.org/10.3389/fncel.2015.00087
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Sidney
Pevny LH, Nicolis SK (2010) Sox2 roles in neural stem cells. Int J Biochem Cell Biol 42:421–424. https://doi.org/10.1016/j.biocel.2009.08.018
Polito A, Reynolds R (2005) NG2-expressing cells as oligodendrocyte progenitors in normal and demyelinated central nervous system. J Anat 207:707–716
Reuss BM (2009) Glial growth factors. In: Squire LR (ed) Encyclopedia of neuroscience. Academic Press, Oxford, pp 819–825
Sánchez-Huerta K, García-Martínez Y, Vergara P, Segovia J, Pacheco-Rosado J (2016) Thyroid hormones are essential to preserve non-proliferative cells of adult neurogenesis of the dentate gyrus. Mol Cell Neurosci 76:1–10. https://doi.org/10.1016/j.mcn.2016.08.001
Scharfman HE (2016) The enigmatic mossy cell of the dentate gyrus. Nat Rev Neurosci 17:562–575. https://doi.org/10.1038/nrn.2016.87
Seaberg RM, van der Kooy D (2003) Stem and progenitor cells: the premature desertion of rigorous definitions. Trends Neurosci 26:125–131
Seri B, García-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160
Shapiro LA, Wang L, Ribak CE (2008) Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia 49:33–41. https://doi.org/10.1111/j.1528-1167.2008.01491.x
Stolp HB, Molnár Z (2015) Neurogenic niches in the brain: help and hindrance of the barrier systems. Front Neurosci 9:20. https://doi.org/10.3389/fnins.2015.00020
Suh H, Consiglio A, Ray J, Sawai T, D'Amour KA, Gage FH (2007) In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell 1:515–528. https://doi.org/10.1016/j.stem.2007.09.002
Viganò F, Dimou L (2016) The heterogeneous nature of NG2-glia. Brain Res 1638:129–137. https://doi.org/10.1016/j.brainres.2015.09.012
Wennström M, Hellsten J, Ekdahl CT, Tingström A (2003) Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat hippocampus. Biol Psychiatry 54:1015–1024
Wennström M, Hellsten J, Ekstrand J, Lindgren H, Tingström A (2006) Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures. Biol Psychiatry 59:178–186
Young KM, Psachoulia K, Tripathi RB, Dunn SJ, Cossell L, Attwell D, Tohyama K, Richardson WD (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron 77:873–885. https://doi.org/10.1016/j.neuron.2013.01.006
Acknowledgements
The author would like to thank Mirza Rojas for editing the English version of the text and Lorena Sánchez Lugo for Illustration service. J P-R is fellow of DEDICT-COFFA and EDI, Instituto Politécnico Nacional. This work was supported by CONACyT 168917, SIP 201501033, and INP-027/2020-Program E022. J-P-R and S-H-K are SNI-CONACyT fellows. CONACyT 307247 granted to Y G-M.
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García-Martinez, Y., Sánchez-Huerta, K.B. & Pacheco-Rosado, J. Quantitative characterization of proliferative cells subpopulations in the hilus of the hippocampus of adult Wistar rats: an integrative study. J Mol Hist 51, 437–453 (2020). https://doi.org/10.1007/s10735-020-09895-4
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DOI: https://doi.org/10.1007/s10735-020-09895-4