Distribution of parvalbumin immunoreactivity in the neocortex of hypothyroid adult rats

Berbel, Pere; Marco, Pilar; Cerezo, J R; DeFelipe, Javier

doi:10.1016/0304-3940(96)12318-1

Cited by 73 publications

(60 citation statements)

References 14 publications

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“…In addition, two highly specific cell types, PV and CR subtypes of GABAergic interneurons, important for motor control, are shown to misdevelop as a consequence of TH deficiency. Although TH has been implicated previously in the development of the GABAergic system (Berbel et al, 1996;Guadano-Ferraz et al, 2003;Venero et al, 2005;Gilbert et al, 2007), we show here that this property is specific for the PV and CR subtypes, and that the unliganded TR␣1 exerts distinct effects on these two cell types with a developmental delay affecting PV-IR cells and an increase in the number of CR-IR cells in the adult mouse. In contrast to this, in the cerebellum, the development of both PV-, CB-, and CR-IR cells were equally delayed, which reflects the general effect of the TR␣1 aporeceptor to retard development.…”

Section: Discussioncontrasting

confidence: 47%

Locomotor Deficiencies and Aberrant Development of Subtype-Specific GABAergic Interneurons Caused by an Unliganded Thyroid Hormone Receptor α1

Wallis¹,

Sjögren²,

Hogerlinden³

et al. 2008

J. Neurosci.

110

102

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Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor ␣1 (TR␣1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TR␣1 as the receptor isoform mediating these effects.

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Section: Discussioncontrasting

confidence: 47%

Locomotor Deficiencies and Aberrant Development of Subtype-Specific GABAergic Interneurons Caused by an Unliganded Thyroid Hormone Receptor α1

Wallis¹,

Sjögren²,

Hogerlinden³

et al. 2008

J. Neurosci.

110

102

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“…These changes were not restricted to the somatosensory area, but were also observed in other cortical regions, such as the motor and the retrosplenial cortex. In previous studies, TH insufficiency during brain development has been demonstrated to reduce PV immunoreactivity in the cerebral cortex of rats (28,29), which suggests that only a subgroup of inhibitory interneurons characterized by PV expression -so-called basket and chandelier cells -is sensitive to TH deprivation. Likewise, mouse mutants expressing a dominant-negative TRα1 protein show only a transient reduction in cortical PV immunoreactivity that normalizes after weaning (30).…”

Section: Discussionmentioning

confidence: 91%

“…ebellar cortex, but also the cerebral cortex, depends on proper TH supply during pre-and postnatal stages. In particular, the differentiation of GABAergic interneurons has been shown to be delayed in hypothyroid rats, as evidenced by reduced parvalbumin (PV) immunoreactivity (28,29). We therefore wondered whether similar alterations also occur in Mct8/Oatp1c1 DKO mice and performed immunohistochemical staining for the calcium-binding proteins PV, calretinin (CR), and CB, which serve as distinct markers for specific subgroups of cortical interneurons.…”

Section: Figurementioning

confidence: 99%

Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis

Mayerl¹,

Müller²,

Bauer³

et al. 2014

J. Clin. Invest.

243

242

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Allan-Herndon-Dudley syndrome (AHDS), a severe form of psychomotor retardation with abnormal thyroid hormone (TH) parameters, is linked to mutations in the TH-specific monocarboxylate transporter MCT8. In mice, deletion of Mct8 (Mct8 KO) faithfully replicates AHDS-associated endocrine abnormalities; however, unlike patients, these animals do not exhibit neurological impairments. While transport of the active form of TH (T3) across the blood-brain barrier is strongly diminished in Mct8 KO animals, prohormone (T4) can still enter the brain, possibly due to the presence of T4-selective organic anion transporting polypeptide (OATP1C1). Here, we characterized mice deficient for both TH transporters, MCT8 and OATP1C1 (Mct8/Oatp1c1 DKO). Mct8/Oatp1c1 DKO mice exhibited alterations in peripheral TH homeostasis that were similar to those in Mct8 KO mice; however, uptake of both T3 and T4 into the brains of Mct8/Oatp1c1 DKO mice was strongly reduced. Evidence of TH deprivation in the CNS of Mct8/Oatp1c1 DKO mice included highly decreased brain TH content as well as altered deiodinase activities and TH target gene expression. Consistent with delayed cerebellar development and reduced myelination, Mct8/Oatp1c1 DKO mice displayed pronounced locomotor abnormalities. Intriguingly, differentiation of GABAergic interneurons in the cerebral cortex was highly compromised. Our findings underscore the importance of TH transporters for proper brain development and provide a basis to study the pathogenic mechanisms underlying AHDS. IntroductionMonocarboxylate transporter 8 (MCT8) is a specific thyroid hormone (TH) transporter that facilitates the passage of the prohormone 3,3′,5,5′-tetraiodothyronine (T4; also known as thyroxine) and the receptor active form, 3,3′,5-triiodothyronine (T3), across the plasma membrane (1). MCT8 is encoded by SLC16A2 (hereafter MCT8) located on human chromosome Xq13.2. Inactivating mutations and deletions in MCT8 result in a distinct clinical picture known as Allan-Herndon-Dudley syndrome (AHDS) (2-5).All affected patients manifest a severe form of psychomotor retardation composed of central hypotonia, spastic tetraplegia, lack of speech development, severe intellectual deficits, and global developmental delays. In addition to the pronounced neurological symptoms, patients exhibit characteristic changes in the serum TH profile, with highly elevated T3 and lowered T4 concentrations. Since 2004, more than 45 families with 125 affected individuals have been reported in the literature, and 1% of cases with the diagnosis of X-linked mental retardation have been estimated to be associated with mutations in MCT8 (6). However, by which pathogenic mechanisms MCT8 deficiency causes AHDS remains largely unknown.MCT8 is present in many organs, such as liver, kidneys, pituitary, and thyroid gland, and is also widely expressed in the CNS. Studies in mouse and human brain tissues revealed MCT8 expression in distinct neuronal populations, with the highest mRNA levels in neo-and allocortical structures (e.g., cerebral cor...

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“…We counted the number of immunoreactive cells found in 500-lm-wide strips (20 strips per group) running perpendicular to the pial surface including all the layers of the primary somatosensory cortex. Also we considered number of cells in every layer (Berbel et al 1996). After measuring the extension of the different layers, we calculated the cellular density in every layer and in the total somatosensory cortex.…”

Section: Density Of Inhibitory Neurons In Ts65dnmentioning

confidence: 99%

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

et al. 2010

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Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4-5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients.

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Distribution of parvalbumin immunoreactivity in the neocortex of hypothyroid adult rats

Cited by 73 publications

References 14 publications

Locomotor Deficiencies and Aberrant Development of Subtype-Specific GABAergic Interneurons Caused by an Unliganded Thyroid Hormone Receptor α1

Locomotor Deficiencies and Aberrant Development of Subtype-Specific GABAergic Interneurons Caused by an Unliganded Thyroid Hormone Receptor α1

Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

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