Abstract
The aim of this study was to evaluate the effects of acute repetitive nociceptive stimuli to newborn rats over neurogenesis rate in the dentate gyrus of hippocampus. Newborn rats were randomly distributed in three groups, according to the type of stimulus received from d 1 to d 7 of life four times per day: acute nociceptive stimuli, tactile stimuli, and none (controls). At d 21 of life, rats received BrdU (5-bromo-2′-deoxyuridine, a marker of cell proliferation), and on d 28, they were killed. After brain sectioning, the tissue was processed for immunohistochemical identification of proliferating cells. BrdU-positive cell counts were performed in the granule cell layer of the dentate gyrus. Acute nociceptive stimulation during the first week of life was not associated to alterations in the weight gain among experimental groups. On examination 1 wk after BrdU injection, the number of BrdU-labeled cells in the dentate gyrus of the hippocampus was not significantly different between stimulated (painful and tactile stimuli) and nonstimulated animals. These results show that both types of stimuli used here, when applied very early in the development, do not affect the neurogenesis rate in the rat dentate gyrus.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BrdU:
-
5-bromo-2′-deoxyuridine
- P:
-
postnatal day of life
References
Prestes AC, Guinsburg R, Balda RC, Marba ST, Rugolo LM, Pachi PR, Bentlin MR 2005 [The frequency of pharmacological pain relief in university neonatal intensive care units]. J Pediatr (Rio J) 81: 405–410
Simons SH, van Dijk M, van Lingen RA, Roofthooft D, Duivenvoorden HJ, Jongeneel N, Bunkers C, Smink E, Anand KJ, van den Anker JN, Tibboel D 2003 Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial. JAMA 290: 2419–2427
Anand KJ 2000 Effects of perinatal pain and stress. Prog Brain Res 122: 117–129
Grunau RE, Whitfield MF, Petrie J 1998 Children's judgments about pain at 8–10 years: Do extremely low birth weight (<1000 g) children differ from full birth weight peers?. J Child Psychol Psychiatry 39: 587–594
Grunau RV, Whitfield MF, Petrie JH, Fryer EL 1994 Early pain experience, child and family factors, as precursors of somatization: a prospective study of extremely premature and full term children. Pain 56: 353–359
Milner B 1972 Disorders of learning and memory after temporal lobe lesions in man. Clin Neurosurg 19: 421–446
Squire LR 1982 The neuropshychology of human memory. Annu Rev Neurosci 5: 241–273
Gould E, Tanapat P, Hastings NB, Shors T 1999 Neurogenesis in adulthood: a possible role in learning. Trends Cogn Sci 3: 186–191
Bruel-Jungerman E, Rampon C, Laroche S 2007 Adult hippocampal neurogenesis, synaptic plasticity and memory: facts and hypotheses. Rev Neurosci 18: 93–114
Altman J, Das GD 1965 Post-natal origin of microneurones in the rat brain. Nature 207: 953–956
Rakic P 1985 DNA synthesis and cell division in the adult primate brain. Ann N Y Acad Sci 457: 193–211
Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH 1998 Neurogenesis in the adult human hippocampus. Nat Med 4: 1313–1317
Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E 1997 Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17: 2492–2498
Gould E, Tanapat P, McEwen BS, Flügge 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
Kempermann G, Kuhn HG, Gage FH 1997 More hippocampal neurons in adult mice living in an enriched environment. Nature 386: 493–495
Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ 1999 Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2: 260–265
van Praag H, Kempermann G, Gage KH 1999 Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2: 266–270
Gould E, Tanapat P, Rydel T, Hastings N 2000 Regulation of hippocampal neurogenesis in adulthood. Biol Psychiatry 48: 715–720
Kanagawa T, Fukuda H, Tsubouchi H, Komoto Y, Hayashi S, Fukui O 2006 A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat. Brain Res 1111: 36–40
Anand KJ, Coskun V, Thrivikraman KV, Nemeroff CB, Plotski PM 1999 Long-term effects of repetitive pain in neonatal rat pups. Physiol Behav 66: 627–637
Parent JM, Janumpalli S, McNamara JO, Lowenstein DH 1998 Increased dentate granule cell neurogenesis following amygdala kindling in the adult rat. Neurosci Lett 247: 9–12
Covolan L, Ribeiro LT, Longo B, Mello LE 2000 Cell damage and neurogenesis in the dentate granule cell layer of adult rats after pilocarpine- or kainate-induced status epilepticus. Hippocampus 10: 169–180
Swanson LW 1992 Brain maps: structure of the rat brain. Elsevier, Amsterdam
Fitzgerald M, Shaw A, McIntosh N 1988 The postnatal developmental of the cutaneous flexor reflex: a comparative study in premature infants and newborn rat pups. Dev Med Child Neurol 30: 520–526
Castro MC, Guinsburg R, Almeida MF, Peres CA, Yanaguibashi G, Kopelman BI 2003 [Profile of opioid prescriptions for intubated and mechanically ventilated neonates]. J Pediatr (Rio J) 79: 41–48
Duric V, McCarson KE 2006 Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression. J Pain 7: 544–555
Acknowledgements
The authors thank Ivone de Paulo for her excellent work in histologic processing. We also thank Adriana Sanudo for graciously performing statistical treatment of the data.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by FAPESP, CAPES, CNPq – Millennium Institute (Brazil).
Rights and permissions
About this article
Cite this article
Leslie, A., Guinsburg, R., Mello, L. et al. Repetitive Nociceptive Stimuli in Newborn Rats Do Not Alter the Hippocampal Neurogenesis. Pediatr Res 63, 154–157 (2008). https://doi.org/10.1203/PDR.0b013e31815ef75d
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e31815ef75d
