Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

Asúa, Teresa; Bilbao, Ainhoa; Gorriti, Miguel Ángel; López-Moreno, J. A.; Álvarez, M.; Navarro, Miguel; Fonseca, Fernando Rodrı́guez de; Pérez-Castillo, Ana

doi:10.1210/en.2007-1586

Cited by 12 publications

(5 citation statements)

References 59 publications

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“…In the QA model, we also found increased [ 18 F]MK-9470 tracer activity in the cerebellum, which inversely correlates to the number of ipsiversive turnings, suggesting that animals with the highest binding were related to a better functional outcome. In agreement with this finding, reduced CB 1 receptor levels in the cerebellum have been shown to be associated with locomotor hyperactivity in congenitally hypothyroid rats [53]. Motor hyperactivity is also a wellcharacterized feature observed in QA-treated animals, which appears already 2 weeks post-lesioning and lasts up to 6 months [54].…”

Section: Discussionsupporting

confidence: 56%

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

Casteels

Martı́nez

Bormans

et al. 2010

Eur J Nucl Med Mol Imaging

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Purpose Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD) receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p<2.10 −5 ), while an increase for these markers was observed on the contralateral side (>5%, all p<7.10 −4 ).[ 18 F]MK-9470 binding was also increased in the cerebellum (p=2.10 −5 ), where it was inversely correlated to the number of ipsiversive turnings (p=7.10 −6 ), suggesting that CB 1 receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p=1.10 −6 ). Conclusion These data point to in vivo changes in endocannabinoid transmission, specifically for CB 1 receptors in the QA model, with involvement of the caudateputamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D 2 and CB 1 neurotransmission in the contralateral hemisphere.

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Section: Discussionsupporting

confidence: 56%

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

Casteels

Martı́nez

Bormans

et al. 2010

Eur J Nucl Med Mol Imaging

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“…For instance, congenital hypothyroidism is associated with impaired expression of the cannabinoid CB 1 receptor in the striatum, resulting in hyperactivity. Administration of thyroid hormone to hypothyroid pups returns both spontaneous activity and CB 1 expression to normal levels (Asu´a et al, 2008). As described in multiple observations, early life stress affects the ECS leading to alterations in emotional processing, stress responses, dopaminergic function, and so on (del Arco et al, 2000;Moreno et al, 2005;Rubio et al, 1995).…”

Section: Impact Of Early Stressmentioning

confidence: 91%

“…Loss or inappropriate secretion of these hormones often results in profound alterations in brain circuitry, affecting motor development, sexual differentiation of the brain or cortical patterning (see McCarthy, 2008 for a review on oestradiol actions on neurodevelopment). Glucocorticoids, thyroid hormones and sex steroids are among the hormones found to regulate brain development, and all clearly affect the ECS (Asu´a et al, 2008;Mailleux and Vanderhaeghen, 1993;Rodriguez de Fonseca et al, 1994). For instance, congenital hypothyroidism is associated with impaired expression of the cannabinoid CB 1 receptor in the striatum, resulting in hyperactivity.…”

Section: Impact Of Early Stressmentioning

confidence: 99%

The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications

Viveros

Llorente

Suárez³

et al. 2011

J Psychopharmacol

114

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This review focuses on the endocannabinoid system as a crucial player during critical periods of brain development, and how its disturbance either by early life stressful events or cannabis consumption may lead to important neuropsychiatric signs and symptoms. First we discuss the advantages and limitations of animal models within the framework of neuropsychiatric research and the crucial role of genetic and environmental factors for the establishment of vulnerable phenotypes. We are becoming aware of important sex differences that have emerged in relation to the psychobiology of cannabinoids. We will discuss sexual dimorphisms observed within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB(1) receptors is regulated throughout development. Then, we discuss recent results showing how an experimental model of early maternal deprivation, which induces long-term neuropsychiatric symptoms, interacts in a sex-dependent manner with the brain endocannabinoid system during development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse. Finally, we discuss the potential implications that organizational and activational actions of gonadal steroids may have in establishing and maintaining sex dependence in the neurobiological actions of cannabinoids and their interaction with stress.

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“…Cycle threshold (dilution 1:10) was around 25. Amplification of the 18S rRNA was used for normalization of cDNA loading in the PCR as previously described [ 56 ]. The relative mRNA content was determined with the 2-ΔΔCt method [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ

Hernández-Encinas

Aguilar-Morante

Morales-García

et al. 2016

J Neuroinflammation

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BackgroundThe CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; although more recent results have revealed an important role for this transcription factor in the brain. Previous studies from our laboratory indicated that CCAAT/enhancer-binding protein β is implicated in inflammatory process and brain injury, since mice lacking this gene were less susceptible to kainic acid-induced injury. More recently, we have shown that the complement component 3 gene (C3) is a downstream target of CCAAT/enhancer-binding protein β and it could be a mediator of the proinflammatory effects of this transcription factor in neural cells.MethodsAdult male Wistar rats (8–12 weeks old) were used throughout the study. C/EBPβ+/+ and C/EBPβ–/– mice were generated from heterozygous breeding pairs. Animals were injected or not with kainic acid, brains removed, and brain slices containing the hippocampus analyzed for the expression of both CCAAT/enhancer-binding protein β and C3.ResultsIn the present work, we have further extended these studies and show that CCAAT/enhancer-binding protein β and C3 co-express in the CA1 and CA3 regions of the hippocampus after an excitotoxic injury. Studies using CCAAT/enhancer-binding protein β knockout mice demonstrate a marked reduction in C3 expression after kainic acid injection in these animals, suggesting that indeed this protein is regulated by C/EBPβ in the hippocampus in vivo.ConclusionsAltogether these results suggest that CCAAT/enhancer-binding protein β could regulate brain disorders, in which excitotoxic and inflammatory processes are involved, at least in part through the direct regulation of C3.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0742-0) contains supplementary material, which is available to authorized users.

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Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

Cited by 12 publications

References 59 publications

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications

Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ

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