TY - JOUR
T1 - The maintenance of hippocampal pyramidal neuron populations is dependent on the modulation of specific cell cycle regulators by thyroid hormones
AU - Alva-Sánchez, Claudia
AU - Sánchez-Huerta, Karla
AU - Arroyo-Helguera, Omar
AU - Anguiano, Brenda
AU - Aceves, Carmen
AU - Pacheco-Rosado, Jorge
N1 - Funding Information:
We thank Dr. Ellis Glazier and Dr. M. Sánchez-Álvarez for editing the English-language text. This work was supported by SIP-IPN 20070734, CONACyT 52253 and PAPIIT 201207. J.P.-R. is a fellow of DEDICT-COFAA-IPN. C.A.-S. is a fellow of CONACYT.
PY - 2009/5/19
Y1 - 2009/5/19
N2 - The onset of adult hypothyroidism causes neuronal damage in the CA3 hippocampal region, which is attenuated by T4 administration. We analyzed the expression of molecular proliferation markers (Cyclin D1 and PCNA), cellular damage-arrest (p53 and p21), and apoptosis (Bax/Bcl-2 index) in the hippocampus of hypothyroid (methimazole; 60 mg/kg) or thyroid replaced (T4, 20 μg/kg; MMI+T4 or T3, 20 μg/kg; MMI+T3) adult male rats. Histological analysis showed that hypothyroid animals exhibit significant neuronal damage in all regions of the hippocampus accompanied by the triggering of the apoptotic pathway (increases in p53, p21 and the Bax/Bcl-2 index) and no changes in proliferation (Cyclin D1 and PCNA). MMI+T4 replaced animals were completely protected with no changes in molecular markers. In contrast, MMI+T3 replaced animals showed partial protection in which, although pro-apoptotic effects remained (increase in the Bax/Bcl-2), proliferative mechanisms were triggered (increase in p53, Cyclin D1 and PCNA expression). Our results indicate that thyroid hormones participate in the maintenance of the hippocampal neuronal population even in adulthood, suggesting that THs have different physiological roles as neuronal survival factors: T4 prevents the activation of apoptotic pathways, whereas T3 activates cell differentiation and proliferation mechanisms.
AB - The onset of adult hypothyroidism causes neuronal damage in the CA3 hippocampal region, which is attenuated by T4 administration. We analyzed the expression of molecular proliferation markers (Cyclin D1 and PCNA), cellular damage-arrest (p53 and p21), and apoptosis (Bax/Bcl-2 index) in the hippocampus of hypothyroid (methimazole; 60 mg/kg) or thyroid replaced (T4, 20 μg/kg; MMI+T4 or T3, 20 μg/kg; MMI+T3) adult male rats. Histological analysis showed that hypothyroid animals exhibit significant neuronal damage in all regions of the hippocampus accompanied by the triggering of the apoptotic pathway (increases in p53, p21 and the Bax/Bcl-2 index) and no changes in proliferation (Cyclin D1 and PCNA). MMI+T4 replaced animals were completely protected with no changes in molecular markers. In contrast, MMI+T3 replaced animals showed partial protection in which, although pro-apoptotic effects remained (increase in the Bax/Bcl-2), proliferative mechanisms were triggered (increase in p53, Cyclin D1 and PCNA expression). Our results indicate that thyroid hormones participate in the maintenance of the hippocampal neuronal population even in adulthood, suggesting that THs have different physiological roles as neuronal survival factors: T4 prevents the activation of apoptotic pathways, whereas T3 activates cell differentiation and proliferation mechanisms.
KW - Apoptosis
KW - Bax/Bcl-2
KW - Cycline D1
KW - Hypothyroidism
KW - PCNA
UR - http://www.scopus.com/inward/record.url?scp=67349142579&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2009.02.043
DO - 10.1016/j.brainres.2009.02.043
M3 - Artículo
C2 - 19269280
SN - 0006-8993
VL - 1271
SP - 27
EP - 35
JO - Brain Research
JF - Brain Research
ER -