PMID- 26658316
OWN - NLM
STAT- MEDLINE
DCOM- 20161018
LR  - 20220331
IS  - 1873-474X (Electronic)
IS  - 0736-5748 (Linking)
VI  - 48
DP  - 2016 Feb
TI  - 1,25-Dihydroxyvitamin D3 exerts neuroprotective effects in an ex vivo model of 
      mild hyperhomocysteinemia.
PG  - 71-9
LID - S0736-5748(15)30109-X [pii]
LID - 10.1016/j.ijdevneu.2015.11.005 [doi]
AB  - Elevated plasma homocysteine (Hcy) levels have been detected in patients with 
      various neurodegenerative conditions. Studies of brain tissue have revealed that 
      hyperhomocysteinemia may impair energy metabolism, resulting in neuronal damage. 
      In addition, new evidence has indicated that vitamin D plays crucial roles in 
      brain development, brain metabolism and neuroprotection. The aim of this study 
      was to investigate the neuroprotective effects of 1,25-dihydroxivitamin D3 
      (calcitriol) in cerebral cortex slices that were incubated with a mild 
      concentration of Hcy. Cerebral cortex slices from adult rats were first 
      pre-treated for 30 min with one of three different concentrations of calcitriol 
      (50 nM, 100 nM and 250 nM), followed by Hcy for 1h to promote cellular 
      dysfunction. Hcy caused changes in bioenergetics parameters (e.g., respiratory 
      chain enzymes) and mitochondrial functions by inducing changes in mitochondrial 
      mass and swelling. Here, we used flow cytometry to analyze neurons that were 
      double-labelled with Propidium Iodide (PI) and found that Hcy induced an increase 
      in NeuN(+)/PI cells but did not affect GFAP(+)/Pi cells. Hcy also induced 
      oxidative stress by increasing reactive oxygen species generation, lipid 
      peroxidation and protein damage and reducing the activity of antioxidant enzymes 
      (e.g., SOD, CAT and GPx). Calcitriol (50 nM) prevented these alterations by 
      increasing the level of the vitamin D receptor. Our findings suggest that using 
      calcitriol may be a therapeutic strategy for treating the cerebral complications 
      caused by Hcy.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Longoni, Aline
AU  - Longoni A
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - Kolling, Janaina
AU  - Kolling J
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - dos Santos, Tiago M
AU  - dos Santos TM
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - dos Santos, Joao Paulo
AU  - dos Santos JP
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - da Silva, Jussemara Souza
AU  - da Silva JS
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - Pettenuzzo, Leticia
AU  - Pettenuzzo L
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - Goncalves, Carlos-Alberto
AU  - Goncalves CA
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - de Assis, Adriano M
AU  - de Assis AM
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - Quincozes-Santos, Andre
AU  - Quincozes-Santos A
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil; Departamento de Bioquimica, ICBS, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
FAU - Wyse, Angela T S
AU  - Wyse AT
AD  - Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do 
      Sul, Porto Alegre, RS 90035-003, Brazil; Departamento de Bioquimica, ICBS, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil. 
      Electronic address: wyse@ufrgs.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151202
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - 0 (Antioxidants)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 36015-30-2 (Propidium)
RN  - EC 1.3.5.1 (Electron Transport Complex II)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Calcitriol/*pharmacology
MH  - Cerebral Cortex/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Electron Transport Complex II/metabolism
MH  - Electron Transport Complex IV/metabolism
MH  - Flow Cytometry
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Homocysteine/*pharmacology
MH  - In Vitro Techniques
MH  - Male
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphopyruvate Hydratase/metabolism
MH  - Propidium/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sodium-Potassium-Exchanging ATPase/metabolism
OTO - NOTNLM
OT  - 1,25-Dihydroxyvitamin D3
OT  - Calcitriol
OT  - Mild hyperhomocysteinemia
OT  - Neuroprotection
OT  - Vitamin D receptor
EDAT- 2015/12/15 06:00
MHDA- 2016/10/19 06:00
CRDT- 2015/12/15 06:00
PHST- 2015/09/10 00:00 [received]
PHST- 2015/11/03 00:00 [revised]
PHST- 2015/11/19 00:00 [accepted]
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2016/10/19 06:00 [medline]
AID - S0736-5748(15)30109-X [pii]
AID - 10.1016/j.ijdevneu.2015.11.005 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2016 Feb;48:71-9. doi: 10.1016/j.ijdevneu.2015.11.005. Epub 
      2015 Dec 2.