PMID- 24339278
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20140317
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Linking)
VI  - 24
IP  - 4
DP  - 2014 Apr
TI  - Repetitive noxious neonatal stimuli increases dentate gyrus cell proliferation 
      and hippocampal brain-derived neurotrophic factor levels.
PG  - 415-23
LID - 10.1002/hipo.22235 [doi]
AB  - Neonatal noxious stimulation has been proposed to model pain triggered by 
      diagnostic/therapeutic invasive procedures in premature infants. Previous studies 
      have shown that hippocampal neurogenesis rate and the behavioral repertoire of 
      adult rats may be altered by neonatal noxious stimuli. The purpose of this study 
      was to evaluate whether noxious stimulation during neonatal period alters the 
      nociceptive response and dentate gyrus neurogenesis when compared to rats 
      subjected to a single noxious stimulus in late infancy. Plasma corticosterone and 
      hippocampal brain-derived neurotrophic factor (BDNF) levels were measured. 
      Neurogenesis in the dentate gyrus was evaluated in adolescent rats (postnatal day 
      40; P40) exposed twice to intra-plantar injections of Complete Freund's adjuvant 
      (CFA) on P1 and P21 (group P1P21) or P8 and P21 (P8P21) or exposed once on P21 
      (pubertal). On P21, one subset of animals received 5-bromo-2'-deoxyuridine (BrdU) 
      and was euthanized on P40 for identification of proliferating cells in the 
      dentate gyrus. Another subset was sampled for thermal response or plasma 
      corticosterone measurement and hippocampal BDNF levels. Proliferative cell rate 
      in dentate gyrus was the highest in all re-exposed groups (P < 0.001), except for 
      P8 females (P8P21F), revealing also a sex difference, where P8P21 males showed 
      higher rate than females (P < 0.001). Stimulated groups took longer than CTL 
      animals to lick the paws (P < 0.001), regardless of the age when the noxious 
      stimulus was applied. Re-exposed groups had lower corticosterone plasma level 
      (P1P21 M and F, P8P21M) than controls. On the contrary, hippocampal BDNF was 
      increased in males from both re-exposed groups. These results show that infant 
      noxious stimulation in neonatally previously stimulated rats is related to high 
      proliferation in the DG and this association seems to be modified by the animal's 
      sex. The new generated dentate granule cells in the hippocampus may have a role 
      in the long-term behavioral responses to neonatal nociceptive stimulation. 
      Noxious stimulation in the neonatal period results in sex-dependent neurogenic 
      response.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Malheiros, J M
AU  - Malheiros JM
AD  - Departamento de Fisiologia, Universidade Federal de Sao Paulo, Sao Paulo, 
      04023-062, Brazil.
FAU - Lima, M
AU  - Lima M
FAU - Avanzi, R D T
AU  - Avanzi RD
FAU - Gomes da Silva, S
AU  - Gomes da Silva S
FAU - Suchecki, D
AU  - Suchecki D
FAU - Guinsburg, R
AU  - Guinsburg R
FAU - Covolan, L
AU  - Covolan L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131223
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corticosterone/blood
MH  - Dentate Gyrus/growth & development/*physiology
MH  - Female
MH  - Freund's Adjuvant
MH  - Hippocampus/growth & development/*physiology
MH  - Male
MH  - Neurogenesis/*physiology
MH  - Neurons/*physiology
MH  - Nociception/*physiology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Sex Factors
OTO - NOTNLM
OT  - hippocampus
OT  - newborn
OT  - nociception
OT  - proliferation
OT  - sex difference
EDAT- 2013/12/18 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/12/17 06:00
PHST- 2013/07/17 00:00 [received]
PHST- 2013/11/22 00:00 [revised]
PHST- 2013/12/02 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1002/hipo.22235 [doi]
PST - ppublish
SO  - Hippocampus. 2014 Apr;24(4):415-23. doi: 10.1002/hipo.22235. Epub 2013 Dec 23.