Effects of a rat model of gestational hypothyroidism on forebrain dopaminergic, GABAergic, and serotonergic systems and related behaviors

Menezes, Edênia da Cunha; Santos, Patrícia Rabelo dos; Goes, Tiago Costa; Carvalho, Vanessa Cibelle Barboza de; Teixeira-Silva, Flávia; Stevens, Hanna E.; Júnior, Daniel Jr. Badauê-Passos

doi:10.1016/j.bbr.2019.03.027

Cited by 22 publications

(14 citation statements)

References 71 publications

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“…These findings significantly support the concept that appropriate thyroid hormones in early postnatal life are vital to the development of the central nervous system, which is required for emotion and motor control [27]. The relationship between thyroid hormone abnormalities, particularly early hypothyroidism, and alterations in anxiety-related behaviors is widely documented but not entirely understood [35]. The amygdala is an important area for anxiety-like behavior.…”

Section: Discussionsupporting

confidence: 61%

Ashwagandha Roots Extract Attenuate Some Anatomical and Behavioral Outcomes in Rat’ Pups After Early Postnatal Induction of Hypothyroidism

Alhahawachee

Taqa

Allaf

2023

Egyptian Journal of Veterinary Sciences

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B ACKGROUND : Thyroid hormones are essential for the growth and maintenance of the central nervous system. Those in charge how quickly brain and neural cells grow and change during development. Aims of the study: To explore the ameliorating effect of Ashwagandha Roots extract (Withania somnifera) in male rats after early postnatal hypothyroidism induced by propylthiouracil. Material and methods: Forty healthy Albino male rat pups were at postnatal day 3(PND3) divided into four groups (10 pups per group): Group 1: Control group, pups received distilled water (D.W.) for 21 days orally then continuous administration for further 21 days. The groups 2, 3, 4 were received Propylthiouracil (1mg/kg) from PND3 for 21 day to induce hypothyroidism state. Then group 2 received D.W. for 21 days from PND24 to PND45 to encounter the same conditions as other groups, while group 3 were received Levothyroxine (4µg/100g/day) orally for further 21days, finally group 4 received Ashwagandha Roots extract (200 mg/kg) orally for 21 day. Hormonal assay, developmental tests, and behavioral tests were done. Result: The present study showed that PTU cause significant decrease in total serum T4 hormone level in the hypothyroid pups in comparison to the control group, these deficiencies during development period in rat's life causes severely impairment in growth and development of the rat's brain as well impairing behavior. Conclusion: The oral administration of Ashwagandha Roots extract showed ameliorating effects compared to levothyroxine effects on Hypothyroidism and related damage in brain maturation.

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Section: Discussionsupporting

confidence: 61%

Ashwagandha Roots Extract Attenuate Some Anatomical and Behavioral Outcomes in Rat’ Pups After Early Postnatal Induction of Hypothyroidism

Alhahawachee

Taqa

Allaf

2023

Egyptian Journal of Veterinary Sciences

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“…From a neurochemical view, a recent study showed that offspring from dams treated with MMI increases GABA A -and dopamine type 2 (specifically D4)-receptor expression in amygdala without change the serotonin receptor expression followed by decrease in anxietylike behaviors (Menezes et al, 2019). Indeed, the same treatment evoked an anxiolytic-like pattern when pups were submitted to the open field, hole board, and elevated plus maze test (Darbra et al, 1995(Darbra et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

“…One of the outcomes of greatest interest has been rodent fear‐ and anxiety‐like behavior that has clinical relevance to mood and anxiety disorders (Hage & Azar, 2012; Mishra et al, 2022). In rodents, deficit of THs has been described to induce an anxiolytic pattern (Darbra et al, 1995, 2003); however, some studies showed that male and female offspring from dams treated with MMI did not shown neither anxious phenotype (Melancia et al, 2017) nor changes in fear conditioning (Menezes et al, 2019). Although adult humans with TH deficiency are more prone to and anxiety and depression (Kirkegaard & Faber, 1981, 1998), it remains unclear whether these outcomes also occur in rodents adulthood offspring.…”

Section: Introductionmentioning

confidence: 99%

Methimazole‐induced gestational hypothyroidism affects the offspring development and differently impairs the conditioned fear in male and female adulthood rodents

Hipólito

Batista

Anjos‐Garcia

et al. 2022

Intl J of Devlp Neuroscience

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Gestational hypothyroidism is a prevalent disorder in pregnant women and also impairs fetal development with relevant outcomes. One of the outcomes of greatest interest has been rodent fear‐ and anxiety‐like behavior. However, the relationship between maternal hypothyroidism and onset of conditioned fear‐related responses in offspring remains controversial. Here, we used a well‐validated methimazole‐induced gestational hypothyroidism to investigate the behavioral consequences in offspring. Dams were treated with methimazole at 0.02% in drinking water up to gestational Day 9. Maternal body weights and maternal behavior were evaluated, and the puppies ware analyzed for weight gain and physical/behavioral development and assigned for the open field and fear conditioning test. Methimazole‐induced gestational hypothyroidism induced loss in maternal and litter weight, increases in maternal behavior, and impairs in offspring developmental landmarks in both male and female rodents. Only male offspring enhanced responsiveness to conditioned fear‐like behavior in adulthood.

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“…In fact, in mammals including human, during the early period, the cerebellum suffers from several developmental processes including migration and differentiation (mainly the granular cells) which make this organ susceptible to injury (34,35). Hypothyroidism may cause long-term cognitive and behavioral shortfall especially during early stages of development including those related to motor function (36,37) and this may be via oxidative action on cerebellum (33). The majority of neurons of human brain is located in the cerebellum and mainly the granular cells (38,39).…”

Section: Discussionmentioning

confidence: 99%

Does Withania somnifera mitigate the structural alterations of the rat brain associated with propylthiouracil?

Khalel¹,

Al-Iraqi²

2022

IJVS

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The repercussion of propylthiouracil (PTU) use postnatally on brain histology have not yet been intensely scrutinized. To examine whether Withania somnifera mitigate the structural effects of propylthiouracil on rat brain, rats were distributed into group A enrolled ten pups that were received -orally-distilled water (D.W) daily from postnatal day (PND) 3 to PND 43. Group B: enrolled pups (n=8) subjected to oral doses of PTU (1 mg/kg/day) from PND 3 to PND 25. Then they were gavaged with D.W till PND 43. Group C: included pups (n=8) that were subjected orally to PTU (1mg/kg/day) PND 3 to PND 25 with receiving levothyroxine (four microgram /100g/day) from PND 25 to PND 43. Group D included pups (n=8) that were treated with oral PTU 1 mg/kg/day PND 3 to PND 25 with receiving Withania somnifera extract (200 mg/kg/day) from PND 25 to PND 43. Cerebellar sections of rats of group B exhibited disorganization of the cerebellar cortex with a falling off in the Purkinje cells' count and the appearance of degenerated cells. Hippocampal sections (of rats of group B) proclaimed a falling off in the breadth of the pyramidal zone of cornu Amonis. Sections of the cerebral cortex of rats in group B exhibited the presence of large degenerated neurons. Sections of rats' brains belonging to groups C and D showed improved cerebellar and cerebral cortex segments and hippocampal and cerebral cortical segments. Levothyroxine and Withania somnifera mitigates the structural changes in the peripubertal rat brain induced by postnatal PTU administration.

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Effects of a rat model of gestational hypothyroidism on forebrain dopaminergic, GABAergic, and serotonergic systems and related behaviors

Cited by 22 publications

References 71 publications

Ashwagandha Roots Extract Attenuate Some Anatomical and Behavioral Outcomes in Rat’ Pups After Early Postnatal Induction of Hypothyroidism

Ashwagandha Roots Extract Attenuate Some Anatomical and Behavioral Outcomes in Rat’ Pups After Early Postnatal Induction of Hypothyroidism

Methimazole‐induced gestational hypothyroidism affects the offspring development and differently impairs the conditioned fear in male and female adulthood rodents

Does Withania somnifera mitigate the structural alterations of the rat brain associated with propylthiouracil?

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