Hypothyroidism impairs late LTP in CA1 region but not in dentate gyrus of the intact rat hippocampus: MAPK involvement

Abstract

Thyroid hormone activates extracellular signal-regulated kinases (ERK1 and ERK2), which are important in late long-term potentiation (L-LTP). The aim of this study was to determine the possible mechanism underlying the impairment of L-LTP as a result of hypothyroidism. We investigated the effect of hypothyroidism on L-LTP of the two associative pathways in the hippocampus: the Schaffer collateral synapses and the perforant path synapses. We also examined the effect of hypothyroidism on ERK1 and ERK2 levels in both the CA1 and dentate gyrus (DG) regions of the hippocampus. Electrophysiological recordings from hippocampi of anesthetized rats show that hypothyroidism impairs L-LTP in CA1 region, but not in the DG. Western blot analysis of the CA1 region shows that hypothyroidism decreases phosphorylated ERK1 and ERK2 levels without affecting their total levels. In the DG of the hypothyroid rat, however, there was no significant change in the levels of phosphorylated or total ERKs. The correlation between the effect of hypothyroidism on L-LTP and enzyme levels suggests that hypothyroidism-induced impairment of L-LTP in CA1 may be due to decreased levels of phosphorylated ERK1 and ERK2.

Maternal marginal iodine deficiency affects the expression of relative proteins during brain development in rat offspring

“…The hippocampus is the part of the brain that is related to cognitive ability, including learning and memory ability (Gerges & Alkadhi 2004). The CA1 area in the hippocampus is important for spatial learning.…”

“…So maternal inadequate intake of iodine leads to insufficient production of thyroid hormones, which is potentially damaging for neurodevelopment of the fetus throughout pregnancy (Morreale et al 2004) and results in permanent and profound effects on neurological functions that contribute to cognitive and neurological impairments (Bernal et al 2003, Tremont et al 2003. The hippocampus is a brain region involved in cognitive skills such as learning and memory (Gerges & Alkadhi 2004) and the CA1 area in the hippocampus is the most important region for spatial learning (Huang et al 1995) where memory is encoded, consolidated, and stored (Vara et al 2003). The maturation and function of the hippocampus are dependent on thyroid hormone (Gerges & Alkadhi 2004).…”

“…The hippocampus is a brain region involved in cognitive skills such as learning and memory (Gerges & Alkadhi 2004) and the CA1 area in the hippocampus is the most important region for spatial learning (Huang et al 1995) where memory is encoded, consolidated, and stored (Vara et al 2003). The maturation and function of the hippocampus are dependent on thyroid hormone (Gerges & Alkadhi 2004). Congenital hypothyroidism can reduce the expression of many proteins in the hippocampus of neonatal rats (Dong et al 2005) and affect its function.…”

Novel two-dimensional morphometric maps and quantitative analysis reveal marked growth and structural recovery of the rat hippocampal regions from early hypothyroid retardation

“…A few previous studies investigated the deleterious effects of thyroid hormone deficiency on the developing hippocampus (HC) (Gould, et al 1991,Lauder & Mugnaini, 1977,1980Rabie et al, 1979;Rami & Rabie, 1988;Rami et al, 1986a,b). Recently several molecular and functional studies have also appeared (Alvarez- Dolado et al, 2001;Alzoubi et al, 2005;Ambrogini et al, 2005;Desouza et al, 2005;Dong et al, 2005;Gerges & Alkadhi, 2004,Gilbert, 2004Gilbert & Paczkowski, 2003;Martinez et al, 2001;Matos, et al 2002;Meaney et al, 2000;Roskoden et al, 1999;Sui & Gilbert, 2003;Uchida et al, 2005;Vaidya et al, 2001;Vara et al, 2002Vara et al, ,2003.…”

Tianeptine induces GluA1 phosphorylation and subsequent alteration of the firing properties of CA1 neurons

“…Stress is an important precipitating factor of major depressive state (Caspi et al, 2003;Kessler, 1997), and is used to induce mood disorder in animal models (Agid et , 2004), which mediate the activity of ion channels and ionotropic receptors (Adams and Sweatt, 2002). Thus, these pathways, in turn, may have negative impact on measures of synaptic plasticity (Gerges and Alkadhi, 2004;Sweatt, 2001). Interfering with the MAPK pathways and with the negative effects of stressors on synaptic plasticity may be beneficial for the treatment of depressive mood disorders (Agid et al, 2007).…”