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Updated: Jun 25, 2026

Optogenetic Entrainment of Hippocampal Theta Oscillations in Behaving Mice
Published on: June 29, 2018
The maintenance of hippocampal pyramidal neuron populations is dependent on the modulation of specific cell cycle
Claudia Alva-Sánchez1, Karla Sánchez-Huerta, Omar Arroyo-Helguera
1Departamento de Fisiología Mauricio Russek, Escuela Nacional de Ciencias Biológicas-IPN, Prol. de Carpio y Plan de Ayala, C.P. 11340, D.F. México, Mexico.
Abstract:
The onset of adult hypothyroidism causes neuronal damage in the CA3 hippocampal region, which is attenuated by T(4) 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 (T(4), 20 microg/kg; MMI+T(4) or T(3), 20 microg/kg; MMI+T(3)) 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+T(4) replaced animals were completely protected with no changes in molecular markers. In contrast, MMI+T(3) 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: T(4) prevents the activation of apoptotic pathways, whereas T(3) activates cell differentiation and proliferation mechanisms.
Insights
Adult hypothyroidism damages hippocampal neurons, but thyroid hormone replacement offers protection. Thyroxine (T4) fully prevents damage, while triiodothyronine (T3) partially protects by promoting cell proliferation.
Area of Science:
- Neuroscience
- Endocrinology
- Cell Biology
Background:
- Adult hypothyroidism can lead to neuronal damage, particularly in the hippocampus.
- Thyroid hormones (THs) are crucial for brain development and function.
- The specific roles of different THs in adult hippocampal neuroprotection are not fully understood.
Purpose of the Study:
- To investigate the effects of hypothyroidism and thyroid hormone replacement on neuronal survival and molecular markers in the adult rat hippocampus.
- To compare the neuroprotective roles of thyroxine (T4) and triiodothyronine (T3) in a hypothyroid model.
Main Methods:
- Adult male rats were made hypothyroid using methimazole (MMI).
- Hormone replacement was achieved with T4 (MMI+T4) or T3 (MMI+T3).
- Hippocampal tissue was analyzed for neuronal damage, proliferation markers (Cyclin D1, PCNA), cell cycle arrest markers (p53, p21), and apoptosis (Bax/Bcl-2 index).
Main Results:
- Hypothyroidism induced significant neuronal damage and apoptosis in the hippocampus, with no change in proliferation.
- T4 replacement completely protected against neuronal damage and normalized molecular markers.
- T3 replacement offered partial protection, reducing apoptosis but also triggering proliferation markers.
Conclusions:
- Thyroid hormones are vital for maintaining adult hippocampal neuronal populations.
- T4 acts as a primary neuronal survival factor by preventing apoptosis.
- T3 plays a role in neuronal differentiation and proliferation, offering partial neuroprotection.
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