Overexpression of the Thyroid Hormone-Responsive (THRSP) Gene in the Striatum Leads to the Development of Inattentive-like Phenotype in Mice

Custodio, Raly James Perez; Botanas, Chrislean Jun; Peña, June Bryan de la; Peña, Irene Joy dela; Kim, Mi-Kyung; Sayson, Leandro Val; Abiero, Arvie; Ryoo, Zae Young; Kim, Boong Nyun; Kim, Hee Jin; Cheong, Jae Hoon

doi:10.1016/j.neuroscience.2018.08.008

Cited by 27 publications

(48 citation statements)

References 36 publications

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“…Thus, increased THRSP expression in the hippocampus of WKY rats could be connected with the disturbances in synaptic plasticity demonstrated in this rat strain (Aleksandrova et al, 2019). Animals with increased THRSP concentrations in the striatum exhibited inattention behavior, but the function of this protein in the hippocampus has not yet been studied (Custodio et al, 2018). However, it should be taken into account that both impaired synaptic plasticity, which is considered crucial in the pathogenesis of depression, and hypothyroidism-induced disturbances in mitochondrial function can be caused by many factors, e.g., elevated glucocorticoid levels or a high-fat diet (HFD).…”

Section: Discussionmentioning

confidence: 99%

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism

et al. 2020

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Although hypothyroidism appears to be an important factor in the pathogenesis of depression, the impact of thyroid hormones on the bioenergetics of the adult brain is still poorly known. Since metabolic changes are reported to be a key player in the manifestation of depressive disorder, we investigated whether there are differences in selected metabolic markers in the frontal cortex and hippocampus of Wistar Kyoto rats (WKY; an animal model of depression) compared to those of control Wistar rats and whether the induction of hypothyroidism by propylthiouracil (PTU) elicits similar effects in these animals or intensifies some parameters in the WKY rats. In our study, we used WKY rats as a model of depression since this strain exhibits lower levels of monoamines in the brain than control rats and exhibits behavioral and hormonal alterations resembling those of depression, including increased reactivity to stress. The findings indicate a decrease in glycolysis intensity in both brain structures in the WKY rats as well as in both strains under hypothyroidism conditions. Furthermore, hypothyroidism disrupted the connection between glycolysis and the Krebs cycle in the frontal cortex and hippocampus in the depression model used in this study. Decreased thyroid hormone action was also shown to attenuate oxidative phosphorylation, and this change was greater in the WKY rats. Our results suggest that both the depression and hypothyroidism models are characterized by similar impairments in brain energy metabolism and mitochondrial function and, additionally, that the co-occurrence of hypothyroidism and depression may exacerbate some of the metabolic changes observed in depression.

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Section: Discussionmentioning

confidence: 99%

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism

et al. 2020

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“…The OFT was used to evaluate the locomotor activity of mice. This test was performed as previously described, with modifications (Botanas et al, 2017; Custodio et al, 2018; Dela Peña et al, 2019; Kim et al, 2019a; Sayson et al, 2019). Mice ( n =8) were were gently placed in the center of the open-field arena and were allowed to explore the whole area for 30 min for 3 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

et al. 2020

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Background: Recently, the recreational use of substituted phenethylamines has grown rapidly. Among these are 2-(3,5-dimethoxy-4-((2-methylallyl)oxy)phenyl)ethanamine (MAL) and 2-(2,5-dimethoxy-4-methylphenyl)-2-methoxyethan-1-amine (BOD). However, studies characterizing their abuse potential are still lacking. Aim: The purpose of this study was to investigate the abuse potential of MAL and BOD. Methods: The psychostimulant, reinforcing, and rewarding properties of MAL and BOD were analyzed using locomotor sensitization, self-administration, and conditioned place preference tests. Dopamine antagonists (i.e. SCH23390, haloperidol) were administered during conditioned place preference to evaluate the involvement of the mesolimbic dopamine system. Furthermore, dopamine-related protein expression in the nucleus accumbens and the ventral tegmental area was measured along with dopamine concentrations in the nucleus accumbens. Electroencephalography was conducted to determine effects of MAL and BOD on brain wave activity. Results: MAL induced psychostimulant effects and sensitization, while BOD induced locomotor depression in mice. Only MAL was self-administered by rats. Both drugs induced conditioned place preference in mice at different doses; dopamine receptor antagonists blocked MAL- and BOD-induced conditioned place preference. Both the compounds altered the expression of dopamine receptor D1 and D2 proteins in the nucleus accumbens and tyrosine hydroxylase (TH) and dopamine transporter in the ventral tegmental area, enhanced dopamine levels in the nucleus accumbens, and increased delta and gamma wave activities in the brain. Conclusions: MAL may induce abuse potential via the mesolimbic dopaminergic system and possibly accompanied by alterations in brain wave activity. Moreover, the lack of rewarding and reinforcing effects in BOD suggest that this drug may have little to no capability to engender compulsive behavior, though having found to induce alterations in dopaminergic system and brain wave activities.

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“…RNA extraction was performed as previously described 29 . Briefly, 1 μg total RNA was reverse transcribed into cDNA using the AccuPower CycleScript RT Premix (Bioneer; Seoul, Korea).…”

Section: Methodsmentioning

confidence: 99%

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

et al. 2019

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An increasing number of N-2-methoxybenzyl-phenethylamine (NBOMe) derivatives are being misused worldwide, including the potent hallucinogen 2-(4-bromo-2,5dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe). However, the number of studies characterizing the abuse potential and psychopharmacological properties of 25B-NBOMe is limited; thus, we examined its rewarding and reinforcing effects using conditioned place preference (CPP) and self-administration (SA) tests. Pretreatment with SCH23390 (SCH), Haloperidol (HAL), and ketanserin (KS), antagonists of dopamine D1 (DRD 1), dopamine D2 (DRD 2), and serotonin 2A (5-HT 2A receptor) receptors, respectively, was utilized during a CPP test to investigate the involvement of the dopaminergic and serotonergic systems in 25B-NBOMemediated effects. We also examined the effects of 25B-NBOMe on the expression of dopamine-related proteins in the nucleus accumbens (NAcc) and ventral tegmental area (VTA). Then, we measured the dopamine level, phosphorylated CREB (p-CREB), deltaFosB (ΔFosB), and brain-derived neurotrophic factor (BDNF) in the NAcc. In addition, we explored the involvement of 5-HT 2A receptors in the 25B-NBOMeinduced head twitch response (HTR). We also examined the effects of 25B-NBOMe on brain wave activity using electroencephalography. 25B-NBOMe elicited CPP and SA. SCH and HAL blocked 25B-NBOMe-induced CPP, whereas KS did not. Moreover, 25B-NBOMe altered the DRD 1 , DRD 2 , and dopamine transporter expression and increased dopamine levels. It also induced changes in p-CREB, ΔFosB, and BDNF expression. 25B-NBOMe induced HTR and increased 5-HT 2A receptor mRNA levels, effects inhibited by KS. Furthermore, 25B-NBOMe altered delta and gamma wave activity, which was normalized by SCH and HAL. These findings show Raly James Perez Custodio and Leandro Val Sayson have contributed equally to this manuscript.

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Overexpression of the Thyroid Hormone-Responsive (THRSP) Gene in the Striatum Leads to the Development of Inattentive-like Phenotype in Mice

Cited by 27 publications

References 36 publications

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism

Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

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