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1.
Lang Speech ; : 238309241270741, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39189455

ABSTRACT

We sought to examine the contribution of visual cues, such as lipreading, in the identification of familiar (words) and unfamiliar (phonemes) words in terms of percent accuracy. For that purpose, in this retrospective study, we presented lists of words and phonemes (adult female healthy voice) in auditory (A) and audiovisual (AV) modalities to 65 Spanish normal-hearing male and female listeners classified in four age groups. Our results showed a remarkable benefit of AV information in word and phoneme recognition. Regarding gender, women exhibited better performance than men in both A and AV modalities, although we only found significant differences for words but not for phonemes. Concerning age, significant differences were detected in word recognition in the A modality between the youngest (18-29 years old) and oldest (⩾50 years old) groups only. We conclude visual information enhances word and phoneme recognition and women are more influenced by visual signals than men in AV speech perception. On the contrary, it seems that, overall, age is not a limiting factor for word recognition, with no significant differences observed in the AV modality.

2.
Nutrients ; 16(2)2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38257082

ABSTRACT

BACKGROUND: In recent decades the number of endurance events has increased, as well as the number of athletes participating in them. Adequate nutritional and water planning is essential to maintain optimal sports performance and to reduce the incidence of gastrointestinal problems. The main objective of this study is to determine the dietary intake and compliance with nutritional recommendations of athletes in two endurance competitions, as well as to assess the incidence of gastrointestinal complaints. METHODS: An observational and cross-sectional study was carried out on the consumption of liquids, food, and supplements in 42 triathletes and mountain runners (MRs) participating in a Vi-Half-Gasteiz triathlon and the Ultra Sierra de Cazorla trail run. At the completion of the trials, participants completed a validated questionnaire (NIQEC). RESULTS: The mean caloric intake during the test of the participants in this study was 192.17 kcal/h, while the mean carbohydrate intake was 43.67 g/h, the mean sodium intake was 267.43 mg/h, and the mean caffeine intake was 15.53 mg/h, with no significant differences between the two sports. The amount of liquids consumed by the participants was 421.21 mL/h, with no significant differences between the triathletes and MRs. As for gastrointestinal problems, it was observed that the participants presented gastrointestinal discomfort in 61.9% of the cases. CONCLUSIONS: The intakes of energy, carbohydrates, water, sodium, and caffeine were lower than the current recommendations. There were no differences in the energy, carbohydrate, water, sodium, and caffeine intakes between the triathletes and mountain runners. Gastrointestinal problems showed a high prevalence in these athletes.


Subject(s)
Caffeine , Dietary Supplements , Humans , Cross-Sectional Studies , Carbohydrates , Sodium , Water
3.
Nutrients ; 15(8)2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37111186

ABSTRACT

BACKGROUND: In the last few years endurance sports have experienced a great increase in the number of competitions and participants. Dietary-nutritional planning is key for performing well during such competitions. To date, there is no questionnaire expressly developed to be able to analyze the consumption of liquids, foods, and supplements, as well as gastrointestinal problems in these events. This study describes the development of the Nutritional Intake Questionnaire for Endurance Competitions (NIQEC). METHODS: The study was composed in the following phases: (1) Bibliographic search for the most important nutrients, (2) focus groups (17 dietitian-nutritionists and 15 experienced athletes) and generation of items, (3) Delphi surveys, and (4) cognitive interviews. RESULTS: After an initial shaping of the questionnaire with the items that emerged in the focus groups, their relevance was evaluated by means of the Delphi survey, which showed more than 80% approval for most items. Finally, the cognitive interviews indicated that the questionnaire was simple and complete for its purpose. The final NIQEC (n = 50 items) was divided in 5 sections: Demographic data; sports data; consumption of liquids, food and supplements before, during, and after the competition; gastrointestinal complaints, and dietary-nutritional planning for the competition. CONCLUSIONS: The NICEQ is a useful tool that allows collecting information from participants on sociodemographic factors and gastrointestinal complaints, and estimating the intake of liquid, food, and supplements, for endurance competitions.


Subject(s)
Physical Endurance , Sports , Humans , Nutritional Status , Eating , Athletes
4.
Biomedicines ; 9(3)2021 Mar 12.
Article in English | MEDLINE | ID: mdl-33809319

ABSTRACT

Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician's direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes.

5.
Article in English | MEDLINE | ID: mdl-33477330

ABSTRACT

Weightlifting is a discipline where technique and anthropometric characteristics are essential to achieve the best results in competitions. This study aims to analyse the relationships between body composition, limb length and barbell kinematics in the performance of weightlifters. It consists of an observational and descriptive study of 19 athletes (12 men [28.50 ± 6.37 years old; 84.58 ± 14.11 kg; 176.18 ± 6.85 cm] and 7 women [27.71 ± 6.34 years old; 64.41 ± 7.63 kg; 166.94 ± 4.11 cm]) who met the inclusion criteria. A level I anthropometrist took anthropometric measures according to the methodology of the International Society for the Advancement of Kinanthropometry (ISAK), and the measurement of the barbell velocity was made with the software Kinovea. In terms of body composition, both genders are within the percentage range of fat mass recommended for this sport. In female weightlifters, there is a positive correlation between foot length, maximal velocity in the Snatch (ρ = 0.775, p = 0.041), and performance indicator in the Snatch and the Clean & Jerk (ρ = 0.964, p < 0.001; ρ = 0.883, p = 0.008, respectively). In male weightlifters, a positive correlation between tibial length and average velocity of the barbell in the Snatch is observed (ρ = 0.848, p < 0.001). Muscle mass percentage correlates positively with performance indicator in both techniques (ρ = 0.634, p = 0.027; ρ = 0.720, p = 0.008). Also, the relative length of the upper limb is negatively correlated with the performance indicator (ρ = -0.602, p = 0.038). Anthropometry and body composition may facilitate skill acquisition among this sport population, contributing to increase the limited body of scientific knowledge related to weightlifting.


Subject(s)
Athletic Performance , Body Composition , Foot/anatomy & histology , Weight Lifting/physiology , Adult , Biomechanical Phenomena , Exercise , Female , Humans , Male
6.
J Pers Med ; 10(3)2020 Sep 04.
Article in English | MEDLINE | ID: mdl-32899797

ABSTRACT

Alzheimer's disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and ß-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aß and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

7.
PLoS One ; 15(7): e0236113, 2020.
Article in English | MEDLINE | ID: mdl-32687511

ABSTRACT

Loss of function mutations in the gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe neurodevelopmental defects in humans associated with a specific thyroid hormone phenotype manifesting high serum 3,5,3'-triiodothyronine (T3) and low thyroxine (T4) levels. Patients present a paradoxical state of peripheral hyperthyroidism and brain hypothyroidism, this last one most likely arising from impaired thyroid hormone transport across the brain barriers. The administration of thyroid hormones by delivery pathways that bypass the brain barriers, such as the intranasal delivery route, offers the possibility to improve the neurological defects of MCT8-deficient patients. In this study, the thyroid hormones T4 and T3 were administrated intranasally in different mouse models of MCT8 deficiency. We have found that, under the present formulation, intranasal administration of thyroid hormones does not increase the content of thyroid hormones in the brain and further raises the peripheral thyroid hormone levels. Our data suggests intranasal delivery of thyroid hormones is not a suitable therapeutic strategy for MCT8 deficiency, although alternative formulations could be considered in the future to improve the nose-to-brain transport.


Subject(s)
Monocarboxylic Acid Transporters/deficiency , Symporters/deficiency , Thyroid Hormones/administration & dosage , Thyroid Hormones/pharmacology , Administration, Intranasal , Animals , Brain/cytology , Mice , Monocarboxylic Acid Transporters/genetics , Mutation , Signal Transduction/drug effects , Symporters/genetics , Thyroid Hormones/blood
8.
Thyroid ; 29(11): 1669-1682, 2019 11.
Article in English | MEDLINE | ID: mdl-31359845

ABSTRACT

Background: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) lead to peripheral hyperthyroidism and profound psychomotor alterations in humans. Mice lacking Mct8 present peripheral hyperthyroidism but no gross neurological abnormalities due to brain compensatory mechanisms involving the enzyme deiodinase type 2 (Dio2). Methods: Here we have analyzed the endocrine and neurologic phenotype of mice lacking both Mct8 and Dio2 at three and six months of age. Thyroxine (T4) and 3,5,3' triiodothyronine (T3) levels/content were measured by specific radioimmunoassays; motor skill performance was evaluated by the footprint, rotarod, four limb hanging wire, and balance beam tests; and brain histological analysis was performed by immunostaining for neurofilament and parvalbumin. Results: We have found that this mouse model presents peripheral hyperthyroidism and brain hypothyroidism. Interestingly, the severity of the brain hypothyroidism seems permanent and varies across regions, with the striatum being a particularly affected area. We have also found brain alterations at the histological level compatible with TH deficiency and impaired motor skills. Conclusions: These findings indicate the potential of Mct8/Dio2-deficient mice to represent a model for human MCT8 deficiency, to understand the mechanisms underlying its pathophysiology, and ultimately design therapeutic interventions for human patients.


Subject(s)
Brain Diseases/genetics , Iodide Peroxidase/genetics , Monocarboxylic Acid Transporters/genetics , Motor Skills , Nervous System Diseases/genetics , Symporters/genetics , Thyroid Hormones/metabolism , Animals , Brain Diseases/pathology , Brain Diseases/psychology , Disease Models, Animal , Female , Iodide Peroxidase/deficiency , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Monocarboxylic Acid Transporters/deficiency , Psychomotor Performance , Symporters/deficiency , Thyroid Gland/pathology , Thyroxine/blood , Triiodothyronine/blood , Iodothyronine Deiodinase Type II
9.
BMC Genomics ; 15: 938, 2014 Oct 26.
Article in English | MEDLINE | ID: mdl-25344729

ABSTRACT

BACKGROUND: Alteromonas macleodii is a ubiquitous gammaproteobacterium shown to play a biogeochemical role in marine environments. Two A. macleodii strains (AltDE and AltDE1) isolated from the same sample (i.e., the same place at the same time) show considerable genomic differences. In this study, we investigate the transcriptional response of these two strains to varying growth conditions in order to investigate differences in their ability to adapt to varying environmental parameters. RESULTS: RNA sequencing revealed transcriptional changes between all growth conditions examined (e.g., temperature and medium) as well as differences between the two A. macleodii strains within a given condition. The main inter-strain differences were more marked in the adaptation to grow on minimal medium with glucose and, even more so, under starvation. These differences suggested that AltDE1 may have an advantage over AltDE when glucose is the major carbon source, and co-culture experiments confirmed this advantage. Additional differences were observed between the two strains in the expression of ncRNAs and phage-related genes, as well as motility. CONCLUSIONS: This study shows that the genomic diversity observed in closely related strains of A. macleodii from a single environment result in different transcriptional responses to changing environmental parameters. This data provides additional support for the idea that greater diversity at the strain level of a microbial community could enhance the community's ability to adapt to environmental shifts.


Subject(s)
Alteromonas/genetics , Genome, Bacterial , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Cluster Analysis , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Genomic Islands , RNA, Untranslated/chemistry , RNA, Untranslated/metabolism , Seawater/microbiology , Sequence Analysis, RNA , Transcriptome
10.
PLoS One ; 8(9): e76021, 2013.
Article in English | MEDLINE | ID: mdl-24069455

ABSTRACT

Although numerous marine bacteria are known to produce antibiotics via hybrid NRPS-PKS gene clusters, none have been previously described in an Alteromonas species. In this study, we describe in detail a novel hybrid NRPS-PKS cluster identified in the plasmid of the Alteromonasmacleodii strain AltDE1 and analyze its relatedness to other similar gene clusters in a sequence-based characterization. This is a mobile cluster, flanked by transposase-like genes, that has even been found inserted into the chromosome of some Alteromonasmacleodii strains. The cluster contains separate genes for NRPS and PKS activity. The sole PKS gene appears to carry a novel acyltransferase domain, quite divergent from those currently characterized. The predicted specificities of the adenylation domains of the NRPS genes suggest that the final compound has a backbone very similar to bleomycin related compounds. However, the lack of genes involved in sugar biosynthesis indicates that the final product is not a glycopeptide. Even in the absence of these genes, the presence of the cluster appears to confer complete or partial resistance to phleomycin, which may be attributed to a bleomycin-resistance-like protein identified within the cluster. This also suggests that the compound still shares significant structural similarity to bleomycin. Moreover, transcriptomic evidence indicates that the NRPS-PKS cluster is expressed. Such sequence-based approaches will be crucial to fully explore and analyze the diversity and potential of secondary metabolite production, especially from increasingly important sources like marine microbes.


Subject(s)
Alteromonas/genetics , Alteromonas/metabolism , Antibiotics, Antineoplastic/biosynthesis , Bleomycin/biosynthesis , Multigene Family , Peptide Synthases/genetics , Polyketide Synthases/genetics , Alteromonas/classification , Amino Acids/chemistry , Antibiotics, Antineoplastic/pharmacology , Bleomycin/pharmacology , Drug Resistance, Bacterial/genetics , Gene Expression Regulation, Bacterial , Gene Order , Peptide Synthases/chemistry , Peptide Synthases/metabolism , Phylogeny , Polyketide Synthases/chemistry , Polyketide Synthases/metabolism , Protein Interaction Domains and Motifs
11.
Endocrinology ; 151(2): 810-20, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20056827

ABSTRACT

Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the second trimester, a period of high sensitivity of the brain to thyroid hormones. In the rat, the equivalent period is the last quarter of pregnancy. However, little is known about thyroid hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated genes have been identified during the postnatal period. To identify potential targets of thyroid hormone in the fetal brain, we induced maternal and fetal hypothyroidism by maternal thyroidectomy followed by antithyroid drug (2-mercapto-1-methylimidazole) treatment. Microarray analysis identified differentially expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after conception. Gene function analysis revealed genes involved in the biogenesis of the cytoskeleton, neuronal migration and growth, and branching of neurites. Twenty percent of the differentially expressed genes were related to each other centered on the Ca(2+) and calmodulin-activated kinase (Camk4) pathway. Camk4 was regulated directly by T(3) in primary cultured neurons from fetal cortex, and the Camk4 protein was also induced by thyroid hormone. No differentially expressed genes were recovered when euthyroid fetuses from hypothyroid mothers were compared with fetuses from normal mothers. Although the results do not rule out a specific contribution from the mother, especially at earlier stages of pregnancy, they indicate that the main regulators of thyroid hormone-dependent, fetal brain gene expression near term are the fetal thyroid hormones.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 4/genetics , Cerebral Cortex/embryology , Gene Expression Regulation , Hypothyroidism/genetics , Animals , Cells, Cultured , Cerebral Cortex/drug effects , Cerebral Cortex/enzymology , DNA Primers , Female , Gene Expression Regulation/drug effects , Humans , Hypothyroidism/embryology , Imidazoles/pharmacology , Neurons/cytology , Neurons/drug effects , Neurons/enzymology , Nucleic Acid Hybridization , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , RNA/genetics , RNA/isolation & purification , Rats , Rats, Wistar , Sex-Determining Region Y Protein/genetics , Thyroidectomy , Thyrotropin/blood , Triiodothyronine/pharmacology
12.
Hepatology ; 43(6): 1257-66, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16729306

ABSTRACT

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.


Subject(s)
Brain Edema/pathology , Hepatic Encephalopathy/pathology , Hyperammonemia/physiopathology , Inflammation Mediators/analysis , Liver Cirrhosis, Experimental/pathology , Analysis of Variance , Animals , Behavior, Animal , Bile Ducts/physiopathology , Brain Edema/physiopathology , Diet , Disease Models, Animal , Hepatic Encephalopathy/physiopathology , Ligation , Liver Cirrhosis, Experimental/physiopathology , Male , Motor Activity/physiology , Random Allocation , Rats , Rats, Wistar , Risk Factors , Statistics, Nonparametric
13.
Eur J Neurosci ; 22(3): 541-51, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16101736

ABSTRACT

Correct positioning of cortical neurons during development depends on the radial migration of the projection neurons and on the coordinated tangential and radial migrations of the subcortically generated interneurons. As previously shown, a transient and moderate maternal deficiency in thyroxin during early corticogenesis alters the radial migration of projection neurons. To determine if a similar effect might also affect tangential migration of medial ganglionic eminence (MGE)-derived neurons at the origin of cortical interneurons, explants of MGE from green fluorescent protein (GFP)-transgenic embryos were implanted into flat cortical mounts from wild-type embryos. The distances covered and the preferential migration (medially) of GFP-MGE neurons from embryos of hypothyroxinemic dams are not affected in their tangential migration into wild-type control cortices. In contrast, when GFP-MGE neurons from embryos of control or hypothyroxinemic dams migrate within cortices from embryos of hypothyroxinemic dams, the GFP-MGE-derived neurons lose their preferential direction of migration, although they still migrate for long distances throughout the cortex. Our results show that maternal hypothyroxinemia alters the tangential migration of GFP-MGE-derived neurons in the neocortex of the progeny and suggest that this alteration is not derived from the migratory neurons themselves but through undefined short- and long-range cues responsible for the guidance of their migration.


Subject(s)
Cell Movement/physiology , Cerebral Cortex/physiology , Hypothyroidism/physiopathology , Median Eminence/cytology , Neurons/physiology , Prenatal Exposure Delayed Effects , Animals , Brain Mapping , Calbindins , Cell Count , Cells, Cultured , Embryo, Mammalian , Female , Green Fluorescent Proteins/biosynthesis , Green Fluorescent Proteins/metabolism , Hypothyroidism/chemically induced , Imidazoles , Immunohistochemistry/methods , Male , Mice , Mice, Inbred ICR , Mice, Transgenic , Pregnancy/blood , Radioimmunoassay/methods , S100 Calcium Binding Protein G/metabolism , Thyroid Hormones/blood , Transplants , Tubulin/metabolism , gamma-Aminobutyric Acid/metabolism
14.
Endocrinology ; 145(9): 4037-47, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15087434

ABSTRACT

Epidemiological studies and case reports show that even a relatively minor degree of maternal hypothyroxinemia during the first half of gestation is potentially dangerous for optimal fetal neurodevelopment. Our experimental approach was designed to result in a mild and transient period of maternal hypothyroxinemia at the beginning of corticogenesis. Normal rat dams received the goitrogen 2-mercapto-1-methyl-imidazole for only 3 d, from embryonic d 12 (E12) to E15. Maternal thyroid hormones decreased transiently to 70% of normal serum values, without clinical signs of hypothyroidism. Dams were injected daily with 5-bromo-2'-deoxyuridine (BrdU) during 3 d, from E14-E16 or E17-E19. Their pups were tested for audiogenic seizure susceptibility 39 d after birth (P39) and killed at P40. Cells that had incorporated BrdU were identified by immunocytochemistry, and quantified: numerous heterotopic cells were found, whether labeled at E14-E16 or E17-E19, that were identified as neurons. The cytoarchitecture and the radial distribution of BrdU-labeled neurons was significantly affected in the somatosensory cortex and hippocampus of 83% of the pups. The radial distribution of gamma-aminobutyric acidergic neurons was, however, normal. The infusion of dams with T4 between E13 and E15 avoided these alterations, which were not prevented when the T4 infusion was delayed to E15-E18. In total, 52% of the pups born to the goitrogen-treated dams responded to an acoustic stimulus with wild runs, followed in some by seizures. When extrapolated to man, these results stress the need for prevention of hypothyroxinemia before midpregnancy, however moderate, and whichever the underlying cause.


Subject(s)
Cell Movement/physiology , Neocortex/abnormalities , Neurons/pathology , Thyroid Gland/embryology , Thyroid Gland/physiology , Animals , Antithyroid Agents/pharmacology , Bromodeoxyuridine/analysis , Epilepsy, Reflex/pathology , Female , Male , Neocortex/pathology , Neocortex/physiology , Pregnancy , Rats , Rats, Wistar , Thyroxine/blood , Triiodothyronine/blood
15.
J Clin Invest ; 111(7): 1073-82, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12671057

ABSTRACT

Epidemiological studies from both iodine-sufficient and -deficient human populations strongly suggest that early maternal hypothyroxinemia (i.e., low circulating free thyroxine before onset of fetal thyroid function at midgestation) increases the risk of neurodevelopmental deficits of the fetus, whether or not the mother is clinically hypothyroid. Rat dams on a low iodine intake are hypothyroxinemic without being clinically hypothyroid because, as occurs in pregnant women, their circulating 3,5,3'-triiodothyronine level is usually normal. We studied cell migration and cytoarchitecture in the somatosensory cortex and hippocampus of the 40-day-old progeny of the iodine-deficient dams and found a significant proportion of cells at locations that were aberrant or inappropriate with respect to their birth date. Most of these cells were neurons, as assessed by single- and double-label immunostaining. The cytoarchitecture of the somatosensory cortex and hippocampus was also affected, layering was blurred, and, in the cortex, normal barrels were not formed. We believe that this is the first direct evidence of an alteration in fetal brain histogenesis and cytoarchitecture that could only be related to early maternal hypothyroxinemia. This condition may be 150-200 times more common than congenital hypothyroidism and ought to be prevented both by mass screening of free thyroxine in early pregnancy and by early iodine supplementation to avoid iodine deficiency, however mild.


Subject(s)
Brain/embryology , Cerebral Cortex/pathology , Hypothyroidism/metabolism , Maternal-Fetal Exchange , Pregnancy Complications/blood , Thyroid Hormones/metabolism , Thyroxine/blood , Thyroxine/metabolism , Animals , Body Weight , Brain/metabolism , Cell Movement , Cerebral Cortex/metabolism , Female , Fetal Diseases/blood , Fetal Diseases/etiology , Hippocampus/embryology , Hippocampus/metabolism , Hypothyroidism/etiology , Immunohistochemistry , Iodine/deficiency , Iodine/pharmacology , Neurons/metabolism , Pregnancy , Rats , Rats, Wistar , Thyroid Gland/embryology , Thyroid Gland/metabolism , Thyroxine/physiology , Time Factors
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