PMID- 28048979
OWN - NLM
STAT- MEDLINE
DCOM- 20171122
LR  - 20211204
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 59
DP  - 2017 Mar
TI  - Adult hippocampal neurogenesis is impaired by transient and moderate 
      developmental thyroid hormone disruption.
PG  - 9-21
LID - S0161-813X(16)30261-3 [pii]
LID - 10.1016/j.neuro.2016.12.009 [doi]
AB  - The hippocampus maintains a capacity for neurogenesis throughout life, a capacity 
      that is reduced in models of adult onset hypothyroidism. The effects of 
      developmental thyroid hormone (TH) insufficiency on neurogenesis in the adult 
      hippocampus, however, has not been examined. Graded degrees of TH insufficiency 
      were induced in pregnant rat dams by administration of 0, 3 or 10ppm of 
      6-propylthiouracil (PTU) in drinking water from gestational day (GD) 6 until 
      weaning. Body, brain, and hippocampal weight were reduced on postnatal day (PN) 
      14, 21, 78 and hippocampal volume was smaller at the 10 but not 3ppm dose level. 
      A second experiment examined adult hippocampal neurogenesis following 
      developmental or adult onset hypothyroidism. Two male offspring from 0 and 3ppm 
      exposed dams were either maintained on control water or exposed to 3ppm PTU to 
      create 4 distinct treatment conditions (Control-Control; Control-PTU, 
      PTU-Control, PTU-PTU) based on developmental and adult exposures. Beginning on 
      the 28th day of adult exposure to 0 or 3ppm PTU, bromodeoxyuridine (BrdU, 
      50mg/kg, ip) was administered twice daily for 5days, and one male from each 
      treatment was sacrificed 24h and 28days after the last BrdU dose and brains 
      processed for immunohistochemistry. Although no volume changes were seen in the 
      hippocampus of the neonate at 3ppm, thinning of the granule cell layer emerged in 
      adulthood. Developmental TH insufficiency produced a reduction in newly born 
      cells, reducing BrdU+ve cells at 1 with no further reduction at 28-days 
      post-BrdU. Similar findings were obtained using the proliferative cell marker 
      Ki67. Neuronal differentiations was also altered with fewer doublecortin (Dcx) 
      expressing cells and a higher proportion of immature Dcx phenotypes seen after 
      developmental but not adult TH insufficiency. An impaired capacity for 
      neurogenesis may contribute to impairments in synaptic plasticity and cognitive 
      deficits previously reported by our laboratory and others following moderate 
      degrees of developmental TH insufficiency induced by this PTU model.
CI  - Published by Elsevier B.V.
FAU - Gilbert, M E
AU  - Gilbert ME
AD  - Toxicity Assessment Division, National Health and Environmental Effects Research 
      Laboratory, US Environmental Protection Agency, Research Triangle Park, NC, USA. 
      Electronic address: gilbert.mary@epa.gov.
FAU - Goodman, J H
AU  - Goodman JH
AD  - Department of Developmental Neurobiology, NY State Institute for Basic Research 
      in Developmental Disabilities, Staten Island, NY 10314, USA; Departments of 
      Physiology and Pharmacology and Neurology, SUNY Downstate Medical Center 
      Brooklyn, NY 11203, USA.
FAU - Gomez, J
AU  - Gomez J
AD  - Department of Developmental Neurobiology, NY State Institute for Basic Research 
      in Developmental Disabilities, Staten Island, NY 10314, USA.
FAU - Johnstone, A F M
AU  - Johnstone AFM
AD  - Toxicity Assessment Division, National Health and Environmental Effects Research 
      Laboratory, US Environmental Protection Agency, Research Triangle Park, NC, USA.
FAU - Ramos, R L
AU  - Ramos RL
AD  - Department of Biomedical Sciences, New York Institute of Technology College of 
      Osteopathic Medicine, Old Westbury, NY 11568, USA.
LA  - eng
PT  - Journal Article
DEP - 20161231
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Antimetabolites)
RN  - 0 (Dcx protein, rat)
RN  - 0 (Doublecortin Domain Proteins)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Thyroid Hormones)
RN  - 721M9407IY (Propylthiouracil)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Antimetabolites/toxicity
MH  - Bromodeoxyuridine/metabolism
MH  - Cell Count
MH  - Cell Differentiation/drug effects
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Doublecortin Domain Proteins
MH  - Doublecortin Protein
MH  - Female
MH  - Hippocampus/embryology/growth & development/*pathology
MH  - Hypothyroidism/blood/chemically induced/*pathology
MH  - Ki-67 Antigen/metabolism
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neurogenesis/*drug effects
MH  - Neuropeptides/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*physiopathology
MH  - Propylthiouracil/toxicity
MH  - Rats
MH  - Rats, Long-Evans
MH  - Thyroid Hormones/blood
OTO - NOTNLM
OT  - Brain development
OT  - Dentate gyrus
OT  - Developmental neurotoxicity
OT  - Hippocampus
OT  - Hypothyroidism
OT  - Neurogenesis
OT  - Thyroid hormone
EDAT- 2017/01/04 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/01/04 06:00
PHST- 2016/10/25 00:00 [received]
PHST- 2016/12/21 00:00 [revised]
PHST- 2016/12/28 00:00 [accepted]
PHST- 2017/01/04 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/01/04 06:00 [entrez]
AID - S0161-813X(16)30261-3 [pii]
AID - 10.1016/j.neuro.2016.12.009 [doi]
PST - ppublish
SO  - Neurotoxicology. 2017 Mar;59:9-21. doi: 10.1016/j.neuro.2016.12.009. Epub 2016 
      Dec 31.