Monoamine concentrations changes in the PTU-induced hypothyroid rat brain and the ameliorating role of folic acid

Tousson, Ehab; Ibrahim, Wafaa; Arafa, Nadia M. S.; Akela, MA

doi:10.1177/0960327111405863

Cited by 38 publications

(39 citation statements)

References 37 publications

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“…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.…”

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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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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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“…Hypothyroidism has been reported to cause mild hyperhomocysteinaemia (increased homocysteine concentration in the blood) [4][5][6][7][8]. The mechanism by which hypothyroidism causes mild hyperhomocysteinaemia is not clear but altered remethylation is likely to be involved.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, complex changes in folic acid metabolism occur in thyroid dysfunction with increases in tetrahydrofolate and decreases in methyltetrahydrofolate in hypothyroid rat liver [9]. Alteration in thyroid hormone level is also known to modulate functions of several tissues in adult animals by modulating their antioxidant defenses [4][5][6][7][8][10][11][12][13]. Overt Thyroid dysfunctions are frequently associated with abnormalities of biochemical liver tests and in severe forms with histologically evident hepatocellular damage the activity of hepatic lipase is decreased [14].…”

Section: Introductionmentioning

confidence: 99%

Folic Acid Alleviates Oxidative Stress and Hyperhomocysteinemia Involved in Liver Dysfunction of Hypothyroid Rats

Tousson¹,

Ibrahim²,

Salama³

et al. 2014

AJBR

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Thyroid hormones are essential for growth and development of the liver. This study evaluated some biochemical alterations in post-pubertal hypothyroidism and its impact on liver functions. Additionally, the ameliorating role of folic acid supplementation was investigated. Fifty male albino rats were randomly divided into five groups (group I, control; group II, folic acid; group III, 0.05% propylthiouracil-induced hypothyroid rats; group IV, Co-treatment; group V post-treatment). There was a significant decrease in plasma T 3 , body weight, fluid and food intakes, folic acid, ALT, total thiol and tFRAP in hypothyroid rats as compared to control group. On the other hand, a significant increase in TSH, relative liver weight, plasma of total homocysteine, serum total protein, AST, total serum bilirubin, cholesterol and tMDA in hypothyroid rats as compared to control group. This reflects hyperhomocysteinemia and oxidative stress associated with hypothyroid state. Folic acid supplemented after restoration of the euthyroid state presented better amelioration over its concurrent supplementation. If confirmed in human beings, our results could propose that folic acid can be used as an adjuvant therapy in hypothyroidism disorders with thyroxin replacement therapy.

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“…The existence of sustained epigenetic mechanisms of gene regulation in neurons has been implicated in the regulation of complex behavior, including abnormalities in mental disorders (eg, autism and ADHD) (Colvis CM 2005;Tsankova N 2007). Recently, Tousson et al (Tousson E 2011) demonstrated that coadministration of folate ameliorated monoamine concentration changes in a PTUtreated model. Since folate participates in the enzymatic demethylation of histones, this micronutrient could play a role in the epigenetic control of gene expression.…”

Section: Introductionmentioning

confidence: 99%

“…In addition specific neuronal loss, the activation and/or proliferation of astrocytes per se might indirectly contribute to changes in hippocampal TR signaling. Thyroid hormones are known to modulate a number of neurotransmitter systems, including monoamines (Ahmed OM 2010;Tousson E 2011). Genetic studies imply that variants of both dopamine and serotonin systems may frequently occur in ADHD for neurotransmitter uptake, synthesis, and breakdown functions.…”

Section: Introductionmentioning

confidence: 99%