Upregulation of aryl hydrocarbon receptor nuclear translocator 2 in the hippocampi of post-stroke depression rats

Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.

[1]  Heng-sheng Chen,et al.  Anesthetics alleviate learning and memory impairment induced by electroconvulsive shock by regulation of NMDA receptor-mediated metaplasticity in depressive rats , 2018, Neurobiology of Learning and Memory.

[2]  M. Prigol,et al.  Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster , 2018, Behavioural Brain Research.

[3]  Wen-Juan Liu,et al.  CSF miR-16 expression and its association with miR-16 and serotonin transporter in the raphe of a rat model of depression. , 2018, Journal of affective disorders.

[4]  Heng-sheng Chen,et al.  Changes in synaptic plasticity are associated with electroconvulsive shock-induced learning and memory impairment in rats with depression-like behavior , 2018, Neuropsychiatric disease and treatment.

[5]  A. Wójtowicz,et al.  Depressive-like effect of prenatal exposure to DDT involves global DNA hypomethylation and impairment of GPER1/ESR1 protein levels but not ESR2 and AHR/ARNT signaling , 2017, The Journal of Steroid Biochemistry and Molecular Biology.

[6]  E. Hilario,et al.  Role of Antioxidants in Neonatal Hypoxic–Ischemic Brain Injury: New Therapeutic Approaches , 2017, International journal of molecular sciences.

[7]  Ye Tian,et al.  Autophagy activation involved in hypoxic‐ischemic brain injury induces cognitive and memory impairment in neonatal rats , 2016, Journal of neurochemistry.

[8]  L. Bi,et al.  Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis. , 2016, Brazilian journal of anesthesiology.

[9]  L. O’Neill,et al.  HIF1α and metabolic reprogramming in inflammation. , 2016, The Journal of clinical investigation.

[10]  R. Depping,et al.  A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT , 2016, Cell Death and Disease.

[11]  A. Sureda,et al.  Post-Stroke Depression Modulation and in Vivo Antioxidant Activity of Gallic Acid and Its Synthetic Derivatives in a Murine Model System , 2016, Nutrients.

[12]  N. Herrmann,et al.  Post-stroke depression, obstructive sleep apnea, and cognitive impairment: Rationale for, and barriers to, routine screening , 2016, International journal of stroke : official journal of the International Stroke Society.

[13]  K. Uzawa,et al.  ARNT2 Regulates Tumoral Growth in Oral Squamous Cell Carcinoma , 2016, Journal of Cancer.

[14]  Sainan Liu,et al.  Role of hypothalamic cannabinoid receptors in post-stroke depression in rats , 2016, Brain Research Bulletin.

[15]  R. Robinson,et al.  Post-Stroke Depression: A Review. , 2016, The American journal of psychiatry.

[16]  M. Pak,et al.  Studies on the animal model of post-stroke depression and application of antipsychotic aripiprazole , 2015, Behavioural Brain Research.

[17]  A. Sureda,et al.  Oxidative stress and post-stroke depression: possible therapeutic role of polyphenols? , 2014, Current medicinal chemistry.

[18]  Julie Dela Cruz,et al.  Differential distribution of hypoxia-inducible factor 1-beta (ARNT or ARNT2) in mouse substantia nigra and ventral tegmental area , 2014, Journal of Chemical Neuroanatomy.

[19]  M. Endres,et al.  Of mice and men: modelling post‐stroke depression experimentally , 2014, British journal of pharmacology.

[20]  A. Sureda,et al.  Post-stroke depression therapy: where are we now? , 2014, Current neurovascular research.

[21]  R. Depping,et al.  Hypoxia-Inducible Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) (HIF-1β): Is It a Rare Exception? , 2014, Molecular medicine.

[22]  J. Mu,et al.  Decreased expression of neuronal Per-Arnt-Sim domain protein 4 gene in the hippocampus of a post-stroke depression rat model , 2014, Experimental and therapeutic medicine.

[23]  B. Unnikrishnan,et al.  Post-stroke depression and lesion location: A hospital based cross-sectional study , 2013, Indian journal of psychiatry.

[24]  Jing-gui Song,et al.  Correlations between cognitive impairment and brain‑derived neurotrophic factor expression in the hippocampus of post-stroke depression rats. , 2012, Molecular medicine reports.

[25]  L. Kaczmarek,et al.  Post-stroke depression: mechanisms, translation and therapy , 2012, Journal of cellular and molecular medicine.

[26]  A. Hofman,et al.  A Study of the Bidirectional Association Between Hippocampal Volume on Magnetic Resonance Imaging and Depression in the Elderly , 2011, Biological Psychiatry.

[27]  A. Simmons,et al.  Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. , 2011, Archives of general psychiatry.

[28]  E. McAuley,et al.  Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume , 2010, The Journal of Neuroscience.

[29]  Mark D. Huffman,et al.  Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association , 2009, Circulation.

[30]  T. Montine,et al.  Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor and Cognitive Function in Non-Demented Subjects , 2009, PloS one.

[31]  R. Pollenz,et al.  Analysis of Ah receptor-ARNT and Ah receptor-ARNT2 complexes in vitro and in cell culture. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  P. Willner Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS , 2005, Neuropsychobiology.

[33]  M. Simon,et al.  Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M. Simon,et al.  The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia. , 2000, Biochemical and biophysical research communications.

[35]  J. Schwartz,et al.  ARNT2, a transcription factor for brain neuron survival? , 1999, The European journal of neuroscience.

[36]  Man-Hung Eric Tang,et al.  promoters using DeepCAGE Genome-wide detection and analysis of hippocampus core , 2009 .