Thyroid hormone and γ-aminobutyric acid (GABA) interactions in neuroendocrine systems

Wiens, Susanna C.; Trudeau, Vance L.

doi:10.1016/j.cbpa.2006.01.033

Cited by 90 publications

(83 citation statements)

References 88 publications

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“…In agreement with our results, GABAergic processes and terminals have been shown to be reduced in developmental hypothyroidism (23). Moreover, hypothyroidism reduced the inhibitory GABAergic neurons in adult rats (58). In contrast, hypothyroidism increased whole brain (11), cortex and hypothalamus (52) GABA levels.…”

Section: Discussionsupporting

confidence: 80%

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: Discussionsupporting

confidence: 80%

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

Allah¹,

Gomaa²,

Sayed³

2014

Acta Physiologica Hungarica

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“…GABA appears to play a role in the homeostasis of the normal thyroid [13]. The thyroid gland has been shown to both actively take up and synthesize GABA [14,15].…”

Section: Introductionmentioning

confidence: 98%

GABA Receptor Expression in Benign and Malignant Thyroid Tumors

Roberts

Mendonca-Torres

Jensen

et al. 2009

Pathol. Oncol. Res.

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Neurotransmitter systems have recently been shown to be involved in multiple malignancies including breast, colon and prostate cancers. The role of neurotransmitters and neurotrophic factors has not yet been examined in thyroid cancer. To determine the possible involvement of neurotransmitter systems in thyroid carcinogenesis we characterized the patterns of gamma-aminobutyric acid (GABA) receptor expression in normal thyroid and thyroid tumors. We examined the expression patterns of the GABAergic system in 70 human thyroid tumor samples (13 follicular adenomas, 14 follicular carcinomas, 43 papillary carcinomas) and adjacent normal thyroid by immunohistochemistry. GABAergic system mRNA expression in thyroid cancer cell lines derived from primary (FTC133) and metastatic tumors (FTC236 and FTC238) was examined by real time PCR. Overall, GABA receptor expression is increased in tumors compared to normal thyroid tissue. Expression of GABAA receptor beta2 was detected in the vasculature of normal thyroid and thyroid tumors but not in thyroid cancer cells. GABAA alpha2 was detected in metastatic-derived but not in primary-tumor derived cell lines. Expression levels of GABAB R2 and GABA receptor associated protein (GABARAP) are increased in adenomas and thyroid cancer suggesting their role in early stages of thyroid tumorigenesis. This study represents the first demonstration of GABA receptor expression in human thyroid tissue and suggests that the GABAergic system is involved in thyroid carcinogenesis.

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“…At the same time, GABA inhibits thyroid stimulating hormone (TSH)-stimulated TH release from the thyroid gland and TSH secretion from the pituitary. 36 Additional research is required to determine the role of THs in pain production, transmission, and amplification.…”

Section: The Thyrotropin Group (Trh Tsh T3)mentioning

confidence: 99%

Hormones in pain modulation and their clinical implications for pain control: a critical review

Chen¹,

Zhang²,

Wang³

2016

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Recently, more and more studies have found that pain generation, transmission and modulation are under hormonal regulation. Indeed, hormonal dysregulation is a common component of chronic pain syndromes. Studies have attempted to determine whether the relationship between the pain and its perception and hormones is a causative relationship and how these processes interrelate. This review summarizes and analyzes the current experimental data and provides an overview of the studies addressing these questions. The relationship between pain perception and endocrine effects suggests that hormones can be used as important biomarkers of chronic pain syndromes and/or be developed into therapeutic agents in the fight against pain.

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Thyroid hormone and γ-aminobutyric acid (GABA) interactions in neuroendocrine systems

Cited by 90 publications

References 88 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

GABA Receptor Expression in Benign and Malignant Thyroid Tumors

Hormones in pain modulation and their clinical implications for pain control: a critical review

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