Thyroid Hormone Regulation of <i>N</i>‐Methyl‐<scp>d</scp>‐Aspartic Acid Receptor Subunit mRNA Expression in Adult Brain

Lee, P. R.; Brady, Dana; Koenig, James I.

doi:10.1046/j.1365-2826.2003.00959.x

Cited by 64 publications

(59 citation statements)

References 42 publications

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“…The hippocampus is a highly sensitive neural structure that is known to be involved in learning and memory and it is a highly vulnerable brain area to the action of thyroid hormones (46), this may be related to the presence of the high content of thyroid receptors (27). Hippocampal synaptic plasticity is widely assumed to represent a mechanism, by which memory is encoded, consolidated and stored (21).…”

Section: Discussionmentioning

confidence: 99%

The effect of omega-3 on cognition in hypothyroid adult male rats

Allah¹,

Gomaa²,

Sayed³

2014

Acta Physiologica Hungarica

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Thyroid hormones and omega-3 are essential for normal brain functions. Recent studies have suggested that omega-3 may protect against the risk of dementia. The aim of this study was to investigate the effect of hypothyroidism on spatial learning and memory in adult male rats, the underlying mechanisms and the possible therapeutic value of omega-3 supplementation. Thirty male rats were divided into three groups; control, hypothyroid and omega-3 treated. Hypothyroidism induced significant deficits in working and reference memories in radial arm maze, retention deficits in passive avoidance test and impaired intermediate and long-term memories in novel object recognition test. Serum total antioxidant capacity (TAC) and hippocampal serotonin and γ-aminobutyric acid (GABA) levels were decreased in the hypothyroid group as compared to the control group. Moreover, the hippocampus of hypothyroid rats showed marked structural changes as diffuse vacuolar degeneration and distortion of the pyramidal cells. Immunohistochemistry showed that the expression of Cav1.2 (the voltage dependent LTCC alpha 1c subunit) protein was increased in the hypothyroid group as compared to the control group. Omega-3 supplementation ameliorated memory deficits, increased TAC, decreased the structural changes and decreased the expression of Cav1.2 protein. In conclusion omega-3 could be useful as a neuroprotective agent against hypothyroidism-induced cognitive impairment.Keywords: hypothyroidism, cognition, omega-3, Cav1.2, GABA and serotonin Thyroid hormones play an important role in the development and the normal function of CNS by different mechanisms. They regulate synaptic transmission (15), modulate the synthesis and turnover of neurotransmitters and modify the sensitivity of their receptors (42, 51). They modulate signal transduction pathways in the CNS through Ca 2+ channels. L-type voltagesensitive Ca 2+ (Cav) channel (L-VSCC) mediates long lasting Ca 2+ currents (55) that play important roles in neurotransmitters release, second messenger cascades and gene regulation (28). L-VSCCs localize prominently on neuronal cell bodies and proximal dendrites (24). They consist of five subunits: α1, α2, β, γ and δ (40); α1 subunit is the ion-conducting pore and contains the binding sites for dihydropyridine (9). There are two different L-VSCC α1 subunits: α1C (Cav1.2) and α1D (Cav1.3) (47). Growing evidence has suggested that excessive Ca 2+ influx through L-VSCCs may be detrimental to memory (55). Moreover, L-VSCC currents were reported to be increased in the hippocampus of aged rats and rabbits and thus, had been implicated in aged-related memory deficits (50). Omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions including neural growth (18), neuroprotection and modulation of

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Section: Discussionmentioning

confidence: 99%

The effect of omega-3 on cognition in hypothyroid adult male rats

Allah¹,

Gomaa²,

Sayed³

2014

Acta Physiologica Hungarica

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“…Thyroid hormone treatment failed to normalize these two neurophysiological abnormalities observed in hypothyroid animals [42], as expected from our finding that thyroxine treatment depressed electrical responses within the DG. Although neither the expression of NMDARs nor DG histology was examined in the present study, we believe that one possible mechanism by which the findings of impaired LTP and spatial learning may be explained is through the change in expression of different NMDAR subunits, including NR1 mRNA or NR2B mRNA [38,52,53]. Given that PTP was also affected by thyroxine application, it seems worth considering that some of the effects of thyroxine may involve presynaptic as well as postsynaptic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…It is surprising that even T3-treated rats showed impaired performance on a spatial task when compared to their matched controls [36], a finding that may be explained by the nongenomic effects of thyroid hormones. Several groups have shown that thyroid hormones inhibit L -[ 3 H]glutamate binding [37], regulate N-methyl- D -aspartate (NMDA) receptor subunit expression in the hippocampus [38], and decrease NMDA-evoked currents in rat hippocampal cultures [39]. It is also known that glutamate and glutamatergic receptors are involved in synaptic plasticity in hippocampal neurons [22,23,24].…”

Section: Introductionmentioning

confidence: 99%

Experimentally Induced Hyperthyroidism Disrupts Hippocampal Long-Term Potentiation in Adult Rats

Taşkın

Artis²,

Bitiktas³

et al. 2011

Neuroendocrinology

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Background: Manipulating thyroid hormones has been shown to influence learning and memory. Although a large body of literature is available on the effects of thyroid hormone deficiency on learning and memory functions during developmental or adult-onset hypothyroidism, electrophysiological findings are limited. This limitation is especially notable with respect to thyroxine administration in adult, normothyroid animals. Methods: Experiments were carried out on 12 adult male Wistar rats, each 9–10 months of age. Rats were randomly divided into hyperthyroid (0.2 mg/kg/day intraperitoneal thyroxine injection, for 21 days) and control groups (n = 6 animals in each group). Following spatial learning performance tests on hyperthyroid and control groups, rats were anesthetized with urethane and placed in a stereotaxic frame. A bipolar, tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted within the granule cell layer of the ipsilateral dentate gyrus to record field excitatory postsynaptic potentials (fEPSP). Following a 15-min baseline recording of fEPSPs, long-term potentiation (LTP) was induced by four sets of tetanic pulse trains. Results: Thyroxine-treated rats showed significantly worse performance in the spatial memory task and attenuated input-output relationships in the electrophysiological analyses. Treated rats also showed a lower efficacy of LTP induction when compared with controls. Conclusion: The present study provides clear in vivo evidence for the action of L-thyroxine in the impairment of synaptic plasticity and in inducing spatial memory task deficits in adult rats. These findings may explain the complaints of cognitive function reductions in hyperthyroid patients.

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“…It has been shown that hypothyroidism is associated with changes of gene expression in both central and peripheral nervous system (Kobayashi et al, 2005). Inability to produce LTP in rat hippocampus and impaired learning and memory in both rats and man are among functional consequences of adult-onset hypothyroidism (Lee et al, 2003). The other researchers believe that hypothyroidism affects behavioral conditions (Burmeister et al, 2001;Smith et al, 2002;Whybrow and Bauer, 2005) and is accompanied by emotional symptoms, including lethargy and dysphoria (Capet et al, 2000;Dugbartey, 1998;Haggerty et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze

et al. 2010

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Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.

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Thyroid Hormone Regulation of N‐Methyl‐d‐Aspartic Acid Receptor Subunit mRNA Expression in Adult Brain

Cited by 64 publications

References 42 publications

The effect of omega-3 on cognition in hypothyroid adult male rats

The effect of omega-3 on cognition in hypothyroid adult male rats

Experimentally Induced Hyperthyroidism Disrupts Hippocampal Long-Term Potentiation in Adult Rats

The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze

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