PMID- 30949917
OWN - NLM
STAT- MEDLINE
DCOM- 20191122
LR  - 20200225
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 39
IP  - 5
DP  - 2019 Jul
TI  - Chronic mild Hyperhomocysteinemia impairs energy metabolism, promotes DNA damage 
      and induces a Nrf2 response to oxidative stress in rats brain.
PG  - 687-700
LID - 10.1007/s10571-019-00674-8 [doi]
AB  - Homocysteine (HCY) has been linked to oxidative stress and varied metabolic 
      changes that are dependent on its concentration and affected tissues. In the 
      present study we evaluate parameters of energy metabolism [succinate 
      dehydrogenase (SDH), complex II and IV (cytochrome c oxidase), and ATP levels] 
      and oxidative stress [DCFH oxidation, nitrite levels, antioxidant enzymes and 
      lipid, protein and DNA damages, as well as nuclear factor erythroid 2-related 
      (Nrf2) protein abundance] in amygdala and prefrontal cortex of HCY-treated rats. 
      Wistar male rats were treated with a subcutaneous injection of HCY (0.03 micromol/g 
      of body weight) from the 30th to 60th post-natal day, twice a day, to induce mild 
      hyperhomocysteinemia (HHCY). The rats were euthanatized without anesthesia at 
      12 h after the last injection, and amygdala and prefrontal cortex were dissected 
      for biochemical analyses. In the amygdala, mild HHCY increased activities of SDH 
      and complex II and decreased complex IV and ATP level, as well as increased 
      antioxidant enzymes activities (glutathione peroxidase and superoxide dismutase), 
      nitrite levels, DNA damage, and Nrf 2 protein abundance. In the prefrontal 
      cortex, mild HHCY did not alter energy metabolism, but increased glutathione 
      peroxidase, catalase and DNA damage. Other analyzed parameters were not altered 
      by HCY-treatment. Our findings suggested that chronic mild HHCY changes each 
      brain structure, particularly and specifically. These changes may be associated 
      with the mechanisms by which chronic mild HHCY has been linked to the risk factor 
      of fear, mood disorders and depression, as well as in neurodegenerative diseases.
FAU - Dos Santos, Tiago Marcon
AU  - Dos Santos TM
AD  - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de 
      Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio 
      Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, 
      Brazil.
FAU - Siebert, Cassiana
AU  - Siebert C
AD  - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de 
      Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio 
      Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, 
      Brazil.
FAU - de Oliveira, Micaela Federizzi
AU  - de Oliveira MF
AD  - Laboratorio de Hematologia e Citologia Clinica, Universidade Federal do Pampa, BR 
      472, Km 592, Caixa Postal 118, Uruguaiana, RS, 97508-000, Brazil.
FAU - Manfredini, Vanusa
AU  - Manfredini V
AD  - Laboratorio de Hematologia e Citologia Clinica, Universidade Federal do Pampa, BR 
      472, Km 592, Caixa Postal 118, Uruguaiana, RS, 97508-000, Brazil.
FAU - Wyse, Angela T S
AU  - Wyse ATS
AD  - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de 
      Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio 
      Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, 
      Brazil. wyse@ufrgs.br.
LA  - eng
PT  - Journal Article
DEP - 20190404
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Amygdala/enzymology/pathology
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Brain/*metabolism/*pathology
MH  - Cell Nucleus/metabolism
MH  - Chronic Disease
MH  - *DNA Damage
MH  - Energy Metabolism
MH  - Hyperhomocysteinemia/*metabolism/*pathology
MH  - Male
MH  - Models, Biological
MH  - NF-E2-Related Factor 2/*metabolism
MH  - *Oxidative Stress
MH  - Prefrontal Cortex/enzymology/pathology
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Antioxidant enzymes response
OT  - DNA damage
OT  - Energy metabolism
OT  - Homocysteine
OT  - Mild hyperhomocysteinemia
OT  - Nrf2 gene
EDAT- 2019/04/06 06:00
MHDA- 2019/11/23 06:00
CRDT- 2019/04/06 06:00
PHST- 2019/01/16 00:00 [received]
PHST- 2019/03/28 00:00 [accepted]
PHST- 2019/04/06 06:00 [pubmed]
PHST- 2019/11/23 06:00 [medline]
PHST- 2019/04/06 06:00 [entrez]
AID - 10.1007/s10571-019-00674-8 [pii]
AID - 10.1007/s10571-019-00674-8 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2019 Jul;39(5):687-700. doi: 10.1007/s10571-019-00674-8. Epub 
      2019 Apr 4.