A Balancing Act: The Immune System Supports Neurodegeneration and Neurogenesis

Abstract

Decapod crustaceans, like mammals, retain the ability to make new neurons throughout life. In mammals, immune cells are closely associated with stem cells that generate adult-born neurons. In crayfish, evidence suggests that immune cells (hemocytes) originating in the immune system travel to neurogenic regions and transform into neural progenitor cells. This nontraditional immune activity takes place continuously under normal physiological conditions, but little is known under pathological conditions (neurodegeneration). In this study, the immune system and its relationship with neurogenesis were investigated during neurodegeneration (unilateral antennular ablation) in adult crayfish. Our experiments show that after ablation (1) Proliferating cells decrease in neurogenic areas of the adult crayfish brain; (2) The immune response, but not neurogenesis, is ablation-side dependent; (3) Inducible nitric oxide synthase (iNOS) plays a crucial role in the neurogenic niche containing neural progenitors during the immune response; (4) Brain areas targeted by antennular projections respond acutely (15 min) to the lesion, increasing the number of local immune cells; (5) Immune cells are recruited to the area surrounding the ipsilateral neurogenic niche; and (6) The vasculature in the niche responds acutely by dilation and possibly also neovascularization. We conclude that immune cells are important in both neurodegeneration and neurogenesis by contributing in physiological conditions to the maintenance of the number of neural precursor cells in the neurogenic niche (neurogenesis), and in pathological conditions (neurodegeneration) by coordinating NO release and vascular responses associated with the neurogenic niche. Our data suggest that neural damage and recovery participate in a balance between these competing immune cell roles.

This is a preview of subscription content, log in to check access.

Fig. 1

adapted from Beltz and Benton 2017; c and d from Sullivan et al. 2007b)

Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Abbreviations

AL:

Accessory lobe

APC:

Anterior proliferation center

BrdU:

Bromodeoxyuridine

CL9:

Cluster 9

CL10:

Cluster 10

CL16:

Cluster 16

EDTA:

Ethylenediaminetetraacetic acid

eNOS:

Endothelial nitric oxide synthase

FITC:

Fluorescein isothiocyanate

GS:

Glutamine synthetase

HPT:

Hematopoietic tissue

iNOS:

Inducible nitric oxide synthase

LAN:

Lateral antennular neuropil

MAN:

Medial antennular neuropil

NO:

Nitric oxide

NOS:

Nitric oxide synthase

nNOS:

Neuronal nitric oxide synthase

uNOS:

Universal nitric oxide synthase

OL:

Olfactory lobe

PB:

Phosphate buffer

PBTx:

PB with Triton X-100

PI:

Propidium iodide

TBI:

Traumatic brain injury

THCs:

Total hemocyte counts

References

  1. Abrous DN, Koehl M, Le Moal M (2005) Adult neurogenesis: from precursors to network and physiology. Physiol Rev 85:523–569. https://doi.org/10.1152/physrev.00055.2003

    CAS  Article  PubMed  Google Scholar 

  2. Arbas EA, Humphreys CJ, Ache BW (1988) Morphology and physiological properties of interneurons and olfactory midbrain of the crayfish. J Comp Physiol A 164:231–241. https://doi.org/10.1007/BF00603953

    CAS  Article  PubMed  Google Scholar 

  3. Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:1424–1437. https://doi.org/10.1152/ajpcell.1996.271.5.C1424

    Article  Google Scholar 

  4. Beltz BS, Benton JL (2017) From blood to brain: adult-born neurons in the crayfish brain are the progeny of cells generated by the immune system. Front Neurosci 11:662. https://doi.org/10.3389/fnins.2017.00662

    Article  PubMed  PubMed Central  Google Scholar 

  5. Beltz BS, Sandeman DC (2003) Regulation of life-long neurogenesis in the decapod crustacean brain. Arthropod Struct Dev 32:39–60. https://doi.org/10.1016/S1467-8039(03)00038-0

    Article  PubMed  Google Scholar 

  6. Benton JL, Sandeman DC, Beltz BS (2007) Nitric oxide in the crustacean brain: regulation of neurogenesis and morphogenesis in the developing olfactory pathway. Dev Dyn 236:3047–3060. https://doi.org/10.1002/dvdy.21340

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Benton JL, Zhang Y, Kirkhart CR, Sandeman DC, Beltz BS (2011) Primary neuronal precursors in adult crayfish brain: replenishment from a non-neuronal source. BMC Neurosci 12:53. https://doi.org/10.1186/1471-2202-12-53

    Article  PubMed  PubMed Central  Google Scholar 

  8. Benton JL, Chaves da Silva PG, Sandeman DC, Beltz BS (2013) First-generation neuronal precursors in the crayfish brain are not self-renewing. Int J Dev Neurosci 31:657–666. https://doi.org/10.1016/j.ijdevneu.2012.11.010

    CAS  Article  PubMed  Google Scholar 

  9. Benton JL, Kery R, Li J, Noonin C, Söderhäll I, Beltz BS (2014) Cells from the immune system generate adult-born neurons in crayfish. Dev Cell 30:322–333. https://doi.org/10.1016/j.devcel.2014.06.016

    CAS  Article  PubMed  Google Scholar 

  10. Blaustein DN, Derby CD, Simmons RB, Beall AC (1988) Structure of the brain and medulla terminalis of the spiny lobster Panulirus argus and the crayfish Procambarus clarkii, with an emphasis on olfactory centers. J Crustac Biol 8:493–519. https://doi.org/10.1163/193724088X00341

    Article  Google Scholar 

  11. Brenneis G, Beltz BS (2019) Adult neurogenesis in crayfish: origin, expansion and migration of neural progenitor lineages in a pseudostratified neuroepithelium. J Comp Neurol. https://doi.org/10.1002/cne.24820

    Article  PubMed  Google Scholar 

  12. Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Giuffrida Stella AM (2007) Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8:766–775. https://doi.org/10.1038/nrn2214

    CAS  Article  PubMed  Google Scholar 

  13. Cárdenas A, Moro MA, Hurtado O, Leza JC, Lizasoain I (2005) Dual role of nitric oxide in adult neurogenesis. Brain Res Rev 50:1–6. https://doi.org/10.1016/j.brainresrev.2005.03.006

    CAS  Article  PubMed  Google Scholar 

  14. Carpentier PA, Palmer TD (2009) Immune influence on adult neural stem cell regulation and function. Neuron 64:79–92. https://doi.org/10.1016/j.neuron.2009.08.038

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Carreira BP, Carvalho CM, Araújo IM (2012) Regulation of injury-induced neurogenesis by nitric oxide. Stem Cells Int 2012:15. https://doi.org/10.1155/2012/895659

    CAS  Article  Google Scholar 

  16. Cayre M, Strambi C, Charpin P, Augier R, Meyer MR, Edwards JS, Strambi A (1996) Neurogenesis in adult insect mushroom bodies. J Comp Neurol 22:300–310. https://doi.org/10.1002/(SICI)1096-9861(19960722)371:2%3c300:AID-CNE9%3e3.0.CO;2-6

    Article  Google Scholar 

  17. Cernak I, Wang Z, Jiang J, Bian X, Savic J (2001) Ultrastructural and functional characteristics of blast injury-induced neurotrauma. J Trauma 50:695–706. https://doi.org/10.1097/00005373-200104000-00017

    CAS  Article  PubMed  Google Scholar 

  18. Chaves da Silva PG, de Barros CM, Lima FRS, Biancalana A, Martinez AMB, Allodi S (2010) Identity of the cells recruited to a lesion in the central nervous system of a decapod crustacean. Cell Tissue Res 342:179–189. https://doi.org/10.1007/s00441-010-1045-x

    Article  PubMed  Google Scholar 

  19. Chaves da Silva PG, Benton JL, Beltz BS, Allodi S (2012) Adult neurogenesis: ultrastructure of a neurogenic niche and neurovascular relationships. PLoS ONE 7(6):e39267. https://doi.org/10.1371/journal.pone.0039267

    CAS  Article  PubMed Central  Google Scholar 

  20. Chaves da Silva PG, Benton JL, Sandeman DC, Beltz BS (2013a) Adult neurogenesis in the crayfish brain: the hematopoietic anterior proliferation center has direct access to the brain and stem cell niche. Stem Cells Dev 22:1027–1041. https://doi.org/10.1089/scd.2012.0583

    CAS  Article  PubMed  Google Scholar 

  21. Chaves da Silva PG, Corrêa CL, de Carvalho SL, Allodi S (2013b) The crustacean central nervous system in focus: subacute neurodegeneration induces a specific innate immune response. PLoS ONE 8:e80896. https://doi.org/10.1371/journal.pone.0080896

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Chaves da Silva PG, Santos de Abreu I, Cavalcante LA, de Barros CM, Allodi S (2015) Role of hemocytes in invertebrate adult neurogenesis and brain repair. Invertebr Surviv J 12:142–154

    Google Scholar 

  23. Dash PK, Mach SA, Moore AN (2001) Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury. J Neurosci Res 63:313–319. https://doi.org/10.1002/1097-4547(20010215)63:4%3c313:AID-JNR1025%3e3.0.CO;2-4

    CAS  Article  PubMed  Google Scholar 

  24. Doetsch F, Caillé I, Lim DA, García-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716

    CAS  Article  Google Scholar 

  25. Harry GJ (2008) Neurogenesis and brain repair. In: Neuroimmune pharmacology. Springer, Boston, pp. 445–462. https://doi.org/10.1007/978-0-387-72573-4_32.

  26. Harzsch S, Krieger J (2018) Crustacean olfactory systems: a comparative review and a crustacean perspective on olfaction in insects. Prog Neurobiol 161:23–60. https://doi.org/10.1016/j.pneurobio.2017.11.005

    CAS  Article  PubMed  Google Scholar 

  27. Hillyer JF, Estévez-Lao TY (2010) Nitric oxide is an essential component of the hemocyte-mediated mosquito immune response against bacteria. Dev Comp Immunol 34:141–149. https://doi.org/10.1016/j.dci.2009.08.014

    CAS  Article  PubMed  Google Scholar 

  28. Horgusluoglu E, Nudelman K, Nho K, Saykin AJ (2017) Adult neurogenesis and neurodegenerative diseases: a systems biology perspective. Am J Med Genet Part B 174:93–112. https://doi.org/10.1002/ajmg.b.32429

    CAS  Article  PubMed  Google Scholar 

  29. Howes EA, Chain BM, Smith PJS, Treherne JE (1987) Blood cells contribute to glial repair in an insect. Tissue Cell 19:877–880. https://doi.org/10.1016/0040-8166(87)90026-7

    CAS  Article  PubMed  Google Scholar 

  30. Ibrahim S, Hu W, Wang X, Gao X, He C, Chen J (2016) Traumatic brain injury causes aberrant migration of adult-born neurons in the hippocampus. Sci Rep 6:21793. https://doi.org/10.1038/srep21793

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Jin X, Yu Z-F, Chen F, Lu G-X, Ding X-Y, Xie L-J, Sun J-T (2017) Neuronal nitric oxide synthase in neural stem cells induces neuronal fate commitment via the inhibition of histone deacetylase 2. Front Cell Neurosci 11:66. https://doi.org/10.3389/fncel.2017.00066

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Johansson KU, Carlberg M (1994) NADPH-diaphorase histochemistry and nitric oxide synthase activity in deutocerebrum of the crayfish, Pacifastacus leniusculus (Crustacea, Decapoda). Brain Res 649:36–42

    CAS  Article  Google Scholar 

  33. Johansson MW, Keyser P, Sritunyalucksana K, Söderhäll K (2000) Crustacean haemocytes and haematopoiesis. Aquaculture 191:45–52. https://doi.org/10.1016/S0044-8486(00)00418-X

    CAS  Article  Google Scholar 

  34. Kelm M (1999) Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1411:273–289. https://doi.org/10.1016/S0005-2728(99)00020-1

    CAS  Article  PubMed  Google Scholar 

  35. Leiter O, Kempermann G, Walker TL (2016) A common language: how neuroimmunological cross talk regulates adult hippocampal neurogenesis. Stem Cells Int 2016:1–13. https://doi.org/10.1155/2016/1681590

    Article  Google Scholar 

  36. Lin X, Söderhäll I (2011) Crustacean hematopoiesis and the astakine cytokines. Blood 117:6417–6424. https://doi.org/10.1182/blood-2010-11-320614

    CAS  Article  PubMed  Google Scholar 

  37. Lind M, Hayes A, Caprnda M, Petrovic D, Rodrigo L, Kruzliak P, Zulli A (2017) Inducible nitric oxide synthase: good or bad? Biomed Pharmacother 93:370–375. https://doi.org/10.1016/j.biopha.2017.06.036

    CAS  Article  PubMed  Google Scholar 

  38. Lorenzon S, de Guarrini S, Smith VJ, Ferrero EA (1999) Effects of LPS injection on circulating haemocytes in crustaceans in vivo. Fish Shellfish Immunol 9:31–50. https://doi.org/10.1006/FSIM.1998.0168

    Article  Google Scholar 

  39. Mellon D, Munger SD (1990) Nontopographic projection of olfactory sensory neurons in the crayfish brain. J Comp Neurol 296:253–262. https://doi.org/10.1002/cne.902960205

    Article  PubMed  Google Scholar 

  40. Ming G, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250. https://doi.org/10.1146/annurev.neuro.28.051804.101459

    CAS  Article  PubMed  Google Scholar 

  41. Noonin C, Lin X, Jiravanichpaisal P, Söderhäll K, Söderhäll I (2012) Invertebrate hematopoiesis: an anterior proliferation center as a link between the hematopoietic tissue and the brain. Stem Cells Dev 21:3173–3186. https://doi.org/10.1089/scd.2012.0077

    CAS  Article  PubMed  Google Scholar 

  42. Novas A, Cao A, Barcia R, Ramos-Martinez JI (2004) Nitric oxide release by hemocytes of the mussel Mytilus galloprovincialis Lmk was provoked by interleukin-2 but not by lipopolysaccharide. Int J Biochem Cell Biol 36:390–394

    CAS  Article  Google Scholar 

  43. Palumbo A (2005) Nitric oxide in marine invertebrates: a comparative perspective. Comp Biochem Physiol Part A 142:241–248. https://doi.org/10.1016/j.cbpb.2005.05.043

    CAS  Article  Google Scholar 

  44. Pathania M, Yan LD, Bordey A (2010) A symphony of signals conducts early and late stages of adult neurogenesis. Neuropharmacology 58:865–876. https://doi.org/10.1016/j.neuropharm.2010.01.010

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Persson M, Cerenius L, Söderhäll K (1987) The influence of haemocyte number on the resistance of the freshwater crayfish, Pacifastacus leniusculus Dana, to the parasitic fungus Aphanomyces astaci. J Fish Dis 10:471–477. https://doi.org/10.1111/j.1365-2761.1987.tb01098.x

    Article  Google Scholar 

  46. Price L, Wilson C, Grant G (2016) Blood–brain barrier pathophysiology following traumatic brain injury, translational research in traumatic brain injury. CRC Press, Boca Raton

    Google Scholar 

  47. Richardson RM, Sun D, Bullock MR (2007) Neurogenesis after traumatic brain injury. Neurosurg Clin N Am 18:169–181. https://doi.org/10.1016/J.NEC.2006.10.007

    Article  PubMed  Google Scholar 

  48. Robinson C, Apgar C, Shapiro LA (2016) Astrocyte Hypertrophy contributes to aberrant neurogenesis after traumatic brain injury. Neural Plast 2016:1347987. https://doi.org/10.1155/2016/1347987

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sandeman DC, Denburg JL (1976) The central projections of chemoreceptor axons in the crayfish revealed by axoplasmic transport. Brain Res 115:492–496

    CAS  Article  Google Scholar 

  50. Sandeman D, Sandeman R, Derby C, Schmidt M (1992) Morphology of the brain of crayfish, crabs, and spiny lobsters: a common nomenclature for homologous structures. Biol Bull 183:304–326. https://doi.org/10.2307/1542217

    CAS  Article  PubMed  Google Scholar 

  51. Sandeman R, Clarke D, Sandeman D, Manly M (1998) Growth-related and antennular amputation-induced changes in the olfactory centers of crayfish brain. J Neurosci 18:6195–6206

    CAS  Article  Google Scholar 

  52. Schachtner J, Schmidt M, Homberg U (2005) Organization and evolutionary trends of primary olfactory brain centers in Tetraconata (Crustacea + Hexapoda). Arthropod Struct Dev 34:257–299. https://doi.org/10.1016/j.asd.2005.04.003

    Article  Google Scholar 

  53. Schmidt M (2007) The Olfactory pathway of decapod crustaceans-an invertebrate model for life-long neurogenesis. Chem Sens 32:365–384. https://doi.org/10.1093/chemse/bjm008

    Article  Google Scholar 

  54. Schmidt M, Ache BW (1992) Antennular projections to the midbrain of the spiny lobster. II. Sensory innervation of the olfactory lobe. J Comp Neurol 318:291–303. https://doi.org/10.1002/cne.903180306

    CAS  Article  PubMed  Google Scholar 

  55. Schmidt M, Ache BW (1996a) Processing of antennular input in the brain of the spiny lobster, Panulirus argus. II. The olfactory pathway. J Comp Physiol A 178:605–628. https://doi.org/10.1007/BF00227375

    Article  Google Scholar 

  56. Schmidt M, Ache BW (1996b) Processing of antennular input in the brain of the spiny lobster, Panulirus argus I non–olfactory chemosensory and mechanosensory pathway of the lateral and median antennular neuropils. J Comp Physiol A 178:579–604

    Article  Google Scholar 

  57. Schmidt M, Van Ekeris L, Ache BW (1992) Antennular projections to the midbrain of the spiny lobster. I. sensory innervation of the lateral and medial antennular neuropils. J Comp Neurol 318:277–290

    CAS  Article  Google Scholar 

  58. Shapiro LA (2017) Altered hippocampal neurogenesis during the first 7 days after a fluid percussion traumatic brain injury. Cell Transpl 26:1314–1318. https://doi.org/10.1177/0963689717714099

    Article  Google Scholar 

  59. Smith V, Söderhäll K (1983) Induction of degranulation and lysis of haemocytes in the freshwater crayfish, Astacus astacus by components of the prophenoloxidase activating system in vitro. Cell Tissue Res 233:295–303. https://doi.org/10.1007/BF00238297

    CAS  Article  PubMed  Google Scholar 

  60. Smith PJS, Leech CA, Treherne JE (1984) Glial repair in an insect central nervous system: effects of selective glial disruption. J Neurosci 4:2698–2711. https://doi.org/10.1523/JNEUROSCI.04-11-02698.1984

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. Smith PJ, Howes EA, Treherne JE (1987) Mechanisms of glial regeneration in an insect central nervous system. J Exp Biol 132:59–78. https://doi.org/10.1.1.553.9453

  62. Smith LK, White CW, Villeda SA (2018) The systemic environment: at the interface of aging and adult neurogenesis. Cell Tissue Res 371:105–113. https://doi.org/10.1007/s00441-017-2715-8

    CAS  Article  PubMed  Google Scholar 

  63. Söderhäll K, Smith V, Johansson M (1986) Exocytosis and uptake of bacteria by isolated haemocyte populations of two crustaceans: evidence for cellular co-operation in the defence reactions of arthropods. Cell Tissue Res 245:43–49. https://doi.org/10.1007/BF00218085

    Article  Google Scholar 

  64. Söderhäll I, Bangyeekhun E, Mayo S, Söderhäll K (2003) Hemocyte production and maturation in an invertebrate animal; proliferation and gene expression in hematopoietic stem cells of Pacifastacus leniusculus. Dev Comp Immunol 27:661–672

    Article  Google Scholar 

  65. Stoecklein VM, Osuka A, Lederer JA (2012) Trauma equals danger-damage control by the immune system. J Leukoc Biol 92:539–551. https://doi.org/10.1189/jlb.0212072

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. Sullivan JM, Beltz BS (2001) Neural pathways connecting the deutocerebrum and lateral protocerebrum in the brains of decapod crustaceans. J Comp Neurol 441:9–22. https://doi.org/10.1002/cne.1394

    CAS  Article  PubMed  Google Scholar 

  67. Sullivan JM, Beltz BS (2005) Integration and segregation of inputs to higher-order neuropils of the crayfish brain. J Comp Neurol 481:118–126. https://doi.org/10.1002/cne.20346

    Article  PubMed  Google Scholar 

  68. Sullivan JM, Sandeman DC, Benton JL, Beltz BS (2007a) Adult neurogenesis and cell cycle regulation in the crustacean olfactory pathway: from glial precursors to differentiated neurons. J Mol Histol 38:527–542. https://doi.org/10.1007/s10735-007-9112-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. Sullivan JM, Benton JL, Sandeman DC, Beltz BS (2007b) Adult neurogenesis: a common strategy across diverse species. J Comp Neurol 500:574–584. https://doi.org/10.1002/cne.21187

    Article  PubMed  PubMed Central  Google Scholar 

  70. Taber KH, Warden DL, Hurley RA (2006) Blast-related traumatic brain injury: what is known? J Neuropsychiatry Clin Neurosci 18:141–145. https://doi.org/10.1176/jnp.2006.18.2.141

    Article  PubMed  Google Scholar 

  71. Tota B, Wang T (2005) Nitric oxide: comparative aspects of respiratory and cardiovascular homeostasis. Comp Biochem Physiol Part A 142:99–101. https://doi.org/10.1016/j.cbpa.2005.08.026

    CAS  Article  Google Scholar 

  72. Tuchina O, Koczan S, Harzsch S, Rybak J, Wolff G, Strausfeld N, Hansson B (2015) Central projections of antennular chemosensory and mechanosensory afferents in the brain of the terrestrial hermit crab (Coenobita clypeatus; Coenobitidae, Anomura). Front Neuroanat 9:94–107. https://doi.org/10.3389/fnana.2015.00094

    Article  PubMed  PubMed Central  Google Scholar 

  73. Villasana LE, Kim KN, Westbrook GL, Schnell E (2015) Functional integration of adult-born hippocampal neurons after traumatic brain injury. eNeuro. https://doi.org/10.1523/ENEURO.0056-15.2015.

  74. Wang H-K, Lee Y-C, Huang C-Y, Liliang P-C, Lu K, Chen H-J, Li Y-C, Tsai K (2015) Traumatic brain injury causes frontotemporal dementia and DP-43 proteolysis. Neuroscience 300:94–103. https://doi.org/10.1016/j.neuroscience.2015.05.013

    CAS  Article  PubMed  Google Scholar 

  75. Wang X, Gao X, Michalski S, Zhao S, Chen J (2016) Traumatic brain injury severity affects neurogenesis in adult mouse hippocampus. J Neurotrauma 33:721–733. https://doi.org/10.1089/neu.2015.4097

    Article  PubMed  PubMed Central  Google Scholar 

  76. Yoshino M, Kondoh Y, Hisada M (1983) Projection of statocyst sensory neurons associated with crescent hairs in the crayfish Procambarus clarkii girard. Cell Tissue Res 230:37–48

    CAS  Article  Google Scholar 

  77. Zhang Y, Allodi S, Sandeman DC, Beltz BS (2009) Adult neurogenesis in the crayfish brain: proliferation, migration, and possible origin of precursor cells. Dev Neurobiol 69:415–436. https://doi.org/10.1002/dneu.20717

    Article  PubMed  PubMed Central  Google Scholar 

  78. Zheng W, ZhuGe Q, Zhong M, Chen G, Shao B, Wang H, Mao X, Xie L, Jin K (2013) Neurogenesis in adult human brain after traumatic brain injury. J Neurotrauma 30:1872–1880. https://doi.org/10.1089/neu.2010.1579

    Article  PubMed  PubMed Central  Google Scholar 

  79. Ziv Y, Schwartz M (2008) Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease. Trends Mol Med 14:471–478

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil), Grant number 8698-11-2 (to P. Chaves da Silva), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil), Grant number 304648/2014-0 (to S. Allodi), Fundação Carlos Chagas Filho de Apoio à Pesquisa do Estado do Rio de Janeiro (FAPERJ/Brazil), Grant number E26/202.762/2017 (to S. Allodi), and U.S. National Science Foundation, Grant numbers IOS-1121345 and IOS-1656103 (to B. Beltz). We are grateful to the Rudolf Barth Electron Microscopy Platform of the Oswaldo Cruz Institute/Fiocruz for the electron microscopy facilities.

Author information

Affiliations

Authors

Contributions

PGCS was involved in experimental design, execution, and analysis of all experiments. KH performed the studies described in Figs. 4 and 6c. JLB was involved in experimental design and assisted with some experiments. BSB helped with planning and analysis of experiments and was directly involved in the niche cell and total hemocyte counts. SA contributed to data analysis and overall project planning. PGCS composed the first draft of the manuscript, which was read critically and revised by all authors.

Corresponding author

Correspondence to Silvana Allodi.

Ethics declarations

Conflict of interest

Authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

iNOS labeling in and around the niche increases after antennular ablation. Confocal image showing only the iNOS hannel of the images showed in Fig. 4. (AE) Side ipsilateral to ablation. (F-J) Side contralateral to ablation. (A, F) Controls. Arrows indicate the vascular cavity located centrally in the niche. (B) 1 h after ablation the ipsilateral side shows an increase of iNOS labeling around the niche and within the vascular cavity (arrow). The contralateral side (G) shows weak labeling around the niche and stronger labeling in the vascular cavity (arrow) compared with the control. (C, H) 24 h after ablation a wide area around the niche is bilaterally labeled with anti-iNOS, including the vascular cavity. (D, I) 48 h after ablation the niche cells as well as the area around the niche on both sides of the brain are labeled by anti-iNOS. iNOS labeling is less extensive in the contralateral side 5 d after ablation (E, J) than 48 h after ablation. Scale bars: 50 µm. Supplementary file1 (TIF 7428 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chaves da Silva, P.G., Hsu, K., Benton, J.L. et al. A Balancing Act: The Immune System Supports Neurodegeneration and Neurogenesis. Cell Mol Neurobiol 40, 967–989 (2020). https://doi.org/10.1007/s10571-020-00787-5

Download citation

Keywords

  • Neurogenic niche
  • Immune response
  • Nitric oxide synthase
  • Hemocytes
  • Vasculature
  • Crayfish