PMID- 31599944
OWN - NLM
STAT- MEDLINE
DCOM- 20200806
LR  - 20230216
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Linking)
VI  - 150
IP  - 2
DP  - 2020 Feb 1
TI  - Postweaning Iron Deficiency in Male Rats Leads to Long-Term Hyperactivity and 
      Decreased Reelin Gene Expression in the Nucleus Accumbens.
PG  - 212-221
LID - 10.1093/jn/nxz237 [doi]
AB  - BACKGROUND: Epidemiological research indicates that iron deficiency (ID) in 
      infancy correlates with long-term cognitive impairment and behavioral 
      disturbances, despite therapy. However, the mechanisms underlying these effects 
      are unknown. OBJECTIVE: We investigated how ID affected postweaning behavior and 
      monoamine concentration in rat brains to determine whether ID during the juvenile 
      period affected gene expression and synapse formation in the prefrontal cortex 
      (PFC) and nucleus accumbens (NAcc). METHODS: Fischer 344/Jcl postweaning male 
      rats aged 21-39 d were fed low-iron diets (0.35 mg/kg iron; ID group) or standard 
      AIN-93 G diets [3.5 mg/kg iron; control (CN) group]. After day 39, all rats were 
      fed the iron-adequate diet. The locomotor activity was evaluated by the open 
      field and elevated plus maze tests at 8 and 12 wk of age. Monoamine 
      concentrations in the brain were analyzed using HPLC at 9 and 13 wk of age. 
      Comprehensive gene expression analysis was performed in the PFC and NAcc at 13 wk 
      of age. Finally, we investigated synaptic density in the PFC and NAcc by 
      synaptophysin immunostaining. RESULTS: Behavioral tests revealed a significant 
      reduction of the age-related decline in the total distance traveled in ID rats 
      compared with CN rats (P < 0.05), indicating that ID affected hyperactivity, 
      which persisted into adulthood (13 wk of age). At this age, reelin (Reln) mRNA 
      expression (adjusted P < 0.01) decreased and synaptic density (P < 0.01) 
      increased in the NAcc in the ID group. Regarding the mesolimbic pathway, 
      homovanillic acid concentration increased in the NAcc, whereas the dopamine 
      concentration decreased in the ventral midbrain. CONCLUSIONS: Our results suggest 
      that ID during the postweaning period in male rats, despite complete iron 
      repletion following ID, led to long-term hyperactivity via monoamine disturbance 
      in the brain and an alteration in the synaptic plasticity accompanied by 
      downregulation of Reln expression in the NAcc.
CI  - Copyright (c) American Society for Nutrition 2019.
FAU - Nishikura, Noriko
AU  - Nishikura N
AD  - Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan.
FAU - Hino, Kodai
AU  - Hino K
AD  - Department of Anatomy, Shiga University of Medical Science, Shiga, Japan.
FAU - Kimura, Tomoko
AU  - Kimura T
AD  - Department of Anatomy, Shiga University of Medical Science, Shiga, Japan.
FAU - Uchimura, Yasuhiro
AU  - Uchimura Y
AD  - Department of Anatomy, Shiga University of Medical Science, Shiga, Japan.
FAU - Hino, Shinjiro
AU  - Hino S
AD  - Department of Medical Cell Biology, Institute of Molecular Embryology and 
      Genetics, Kumamoto University, Kumamoto, Japan.
FAU - Nakao, Mitsuyoshi
AU  - Nakao M
AD  - Department of Medical Cell Biology, Institute of Molecular Embryology and 
      Genetics, Kumamoto University, Kumamoto, Japan.
FAU - Maruo, Yoshihiro
AU  - Maruo Y
AD  - Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan.
FAU - Udagawa, Jun
AU  - Udagawa J
AD  - Department of Anatomy, Shiga University of Medical Science, Shiga, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Reelin Protein)
RN  - 0 (Reln protein, rat)
SB  - IM
MH  - Anemia, Iron-Deficiency/*complications/physiopathology
MH  - Animals
MH  - Biogenic Monoamines/metabolism
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Male
MH  - *Motor Activity
MH  - Rats
MH  - Rats, Inbred F344
MH  - Reelin Protein
MH  - Synapses/metabolism
MH  - *Weaning
OTO - NOTNLM
OT  - iron deficiency
OT  - iron deficiency anemia
OT  - nucleus accumbens
OT  - rat
OT  - reelin
EDAT- 2019/10/11 06:00
MHDA- 2020/08/07 06:00
CRDT- 2019/10/11 06:00
PHST- 2019/04/04 00:00 [received]
PHST- 2019/05/23 00:00 [revised]
PHST- 2019/09/06 00:00 [accepted]
PHST- 2019/10/11 06:00 [pubmed]
PHST- 2020/08/07 06:00 [medline]
PHST- 2019/10/11 06:00 [entrez]
AID - S0022-3166(22)02037-5 [pii]
AID - 10.1093/jn/nxz237 [doi]
PST - ppublish
SO  - J Nutr. 2020 Feb 1;150(2):212-221. doi: 10.1093/jn/nxz237.