The NMDA receptor antagonist MK - 801 abolishes the increase in both p53 and Bax/Bcl2 index induced by adult - onset hypothyroidism in rat

• Autorzy: Alva-Sanchez C. , Rodriguez A. , Villanueva I. , Anguiano B. , Acevez C. , Pacheco-Rosado J.
• Języki publikacji: EN

Abstrakty

EN

Hypothyroidism affects neuron population dynamics in the hippocampus of the adult rat, with neuronal damage as the main feature of its effect. This effect is prevented by the blockade of NMDA receptors, which suggests that glutamatergic activity mediates cell death in this condition. Glutamate can also stimulate cell proliferation and survival of newborn neurons, indicating that it can affect different stages of the cell cycle. In this work we measured the expression of specific proteins that control cell proliferation (cycline-Dl), cell arrest (p21), damage (p53) or apoptosis (Bax and Bcl2) in the hippocampus of hypothyroid rats treated with the NMDA receptor (NMDAR) blocker MK-801 during the induction of hypothyroidism. The results show that hypothyroidism increases the expression of markers of DNA damage, cell arrest, and apoptosis, but does not affect the marker of cell proliferation. NMDAR blockade prevents the increase on markers of DNA damage and apoptosis, but does not influence cell arrest or cell proliferation. This suggests that hypothyroidism promotes cell death mainly by an excitotoxic effect of glutamate.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2014
• Tom: 74
• Numer: 1
• Opis fizyczny: p.111-117,fig.,ref.

Twórcy

autor

Alva-Sanchez C.

• Department of Physiology “Mauricio Russek” National School of Biological Sciences, IPN, Mexico, DF, Mexico

autor

Rodriguez A.

• Department of Physiology “Mauricio Russek” National School of Biological Sciences, IPN, Mexico, DF, Mexico

autor

Villanueva I.

• Department of Physiology “Mauricio Russek” National School of Biological Sciences, IPN, Mexico, DF, Mexico

autor

Anguiano B.

• Neurobiology Institute, UNAM-Juriquilla, Queretaro, Mexico

autor

Acevez C.

• Neurobiology Institute, UNAM-Juriquilla, Queretaro, Mexico

autor

Pacheco-Rosado J.

• Department of Physiology “Mauricio Russek” National School of Biological Sciences, IPN, Mexico, DF, Mexico

Bibliografia

• Alva-Sánchez C, Becerril A, Anguiano B, Aceves C, Pacheco-Rosado J (2009a) Participation of NMDA- glutamatergic receptors in hippocampal neuronal damage caused by adult-onset hypothyroidism. Neurosci Lett 453: 178-181.
• Alva-Sánchez C, Ortiz-Butrón R, Pacheco-Rosado J (2004) Kainic acid does not affect CA3 hippocampal region pyramidal cells in hypothyroid rats. Brain Res Bull 63: 167-171.
• Alva-Sánchez C, Sánchez-Huerta K, Arroyo-Helguera O, Anguiano B, Aceves C, Pacheco-Rosado J (2009b) The maintenance of hippocampal pyramidal neuron popula¬tions is dependent on the modulation of specific cell cycle regulators by thyroid hormones. Brain Res 1271: 22-35.
• Ambrogini P, Cuppini R, Ferri P, Manzini C, Ciaroni S, Voci A, Gerdoni E, Gallo G (2005) Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat. Neuroendocrinol 81: 244-253.
• Camacho A, Massieu L (2006) Role of glutamate transporters in the clearance and release of glutamate during ischemia and its relation to neuronal death. Arch Med Res 37: 11-18.
• Caria MA, Dratman MB, Kow LM, Mameli O, Pavlides C (2009) Thyroid hormone action: nongenomic modulation of neuronal excitability in the hippocampus. J Neuroendocrinol 21: 98-107.
• Desouza LA, Ladiwala U, Daniel SM, Agashe S, Vaidya RA, Vaidya VA (2005) Thyroid hormone regulates hip- pocampal neurogenesis in the adult rat brain. Mol Cell Neurosci 29: 414-426.
• Giné E, Morales-Garcia JA, Perez-Castillo A, Santos A (2010) Developmental hypothyroidism increases the expression of kainate receptors in the hippocampus and the sensitivity to kainic acid-induced seizures in the rat. Endocrinology 151: 3267-3276.
• Hardingham GE, Bading H (2003) The Yin and Yang of NMDA receptor signalling. Trends Neurosci 26: 81-89.
• Ivanov A, Pellegrino C, Rama S, Dumalska I, Salyha Y, Ben- Ari Y, Medina I (2006) Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extra¬cellular signal-regulated kinases (ERK) activity in cul¬tured rat hippocampal neurons. J Physiol 572: 789-798.
• Jiang X, Tian F, Mearow K, Okagaki P, Lipsky RH, Marini AM (2005) The excitoprotective effect of N-methyl-D- aspartate receptors is mediated by a brain-derived neu- rotrophic factor autocrine loop in cultured hippocampal neurons. J Neurochem 94: 713-722.
• Kippin TE, Martens DJ, van der Kooy D (2005) p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their prolifera¬tion capacity. Genes Dev 19: 756-767.
• Kobayashi K, Tsuji R, Yoshioka T, Mino T, Seki T (2006) Perinatal exposure to PTU delays switching from NR2B to NR2A subunits of the NMDA receptor in the rat cere¬bellum. Neurotoxicology 27: 284-290.
• Kong WM, Martin NM, Smith KL, Gardiner JV, Connoley IP, Stephens DA, Dhillo WS, Ghatei MA, Small CJ, Bloom SR (2004) Triiodothyronine stimulates food intake via the hypothalamic ventromedial nucleus independent of changes in energy expenditure. Endocrinology 145: 5252-5258.
• Laron Z (2003) Interactions between the thyroid hormones and the hormones of the growth hormone axis. Pediatr Endocrinol Rev 1 (Suppl 2): 244-249.
• Lee PR, Brady D, Koenig JI (2003) Thyroid hormone regu¬lation of N-methyl-D-aspartic acid receptor subunit mRNA expression in adult brain. J Neuroendocrinol 15: 87-92.
• Liu Y, Wong TP, Aarts M, Rooyakkers A, Liu L, Lai TW, Wu DC, Lu J, Tymianski M, Craig AM, Wang YT (2007) NMDA receptor subunits have differential roles in medi¬ating excitotoxic neuronal death both in vitro and in vivo. J Neurosci 27: 2846-2857.
• Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T (1995) p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev 9: 935¬944.
• Miller FD, Pozniak CD, Walsh GS (2000) Neuronal life and death: an essential role for the p53 family. Cell Death Differ 7: 880-888.
• Montero-Pedrazuela A, Venero C, Lavado-Autric R, Fernández-Lamo I, García-Verdugo JM, Bernal J, Guadaño-Ferraz A (2006) Modulation of adult hip¬pocampal neurogenesis by thyroid hormones: implica¬tions in depressive-like behavior. Mol Psychiatry 11: 361-371.
• Nacher J, McEwen BS (2006) The role of N-methyl-D- aspartate receptors in neurogenesis. Hippocampus 16: 267-270.
• Puzianowska-Kuznicka M, Pietrzak M, Turowska O, Nauman A (2006) Thyroid hormones and their receptors in the regulation of cell proliferation. Acta Biochim Pol 53: 641-650.
• Sala-Roca J, Estebanez-Perpina E, Balada F, Garau A, Martí-Carbonell MA (2008) Effects of adult dysthyroid- ism on the morphology of hippocampal neurons. Behav Brain Res 188: 348-354.
• Sánchez-Huerta K, Montes S, Pérez-Severiano F, Alva- Sánchez C, Ríos C, Pacheco-Rosado J (2012) Hypothyroidism reduces glutamate-synaptic release by ouabain depolarization in rat CA3-hippocampal region. J Neurosci Res 90: 905-912.
• Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of Gl-phase progression. Genes Dev 13: 1501-1512.
• Silva JE (2006) Thermogenic mechanisms and their hor¬monal regulation. Physiol Rev 86: 435-464.
• Toms SA, Hercbergs A, Liu J, Kondo S, Barnett GH, Casey G, Barna BP (1998) Thyroid hormone depletion inhibits astrocytoma proliferation via a p53-independent induc¬tion of p21 (WAF1/CIP1). Anticancer Res 18: 289-293.
• Yuan J, Yankner BA (2000) Apoptosis in the nervous sys¬tem. Nature 407: 802 -809.
• Xiang H, Kinoshita Y, Knudson CM, Korsmeyer SJ, Schwartzkroin PA, Morrison RS (1998) Bax involvement in p53-mediated neuronal cell death. J Neurosci 18: 1363-1373.