Antagonist‐induced increase in 5‐HT1A‐receptor expression in adult rat hippocampus and cortex

Abbas, Syed Y.; Nogueira, Maria Inês; Azmitia, Efrain C.

doi:10.1002/syn.20399

Cited by 22 publications

(15 citation statements)

References 40 publications

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“…1996), and thus the lack of 5‐HT in the Pet‐1 knockout mice may also result in up‐regulation of these post‐synaptic 5‐HT1A receptors. In agreement with this, acute treatment with 5‐HT1A antagonist WAY100,635 was also shown to up‐regulate 5‐HT1A receptor number in cortex and hippocampus (Abbas et al. 2007).…”

Section: Discussionsupporting

confidence: 60%

“…Lesion of 5-HT projections to the hippocampus using the 5-HT neurotoxin, 5,7-dihydroxytryptamine, results in increased levels of 5-HT1A protein in the hippocampus (Patel et al 1996), and thus the lack of 5-HT in the Pet-1 knockout mice may also result in up-regulation of these post-synaptic 5-HT1A receptors. In agreement with this, acute treatment with 5-HT1A antagonist WAY100,635 was also shown to upregulate 5-HT1A receptor number in cortex and hippocampus (Abbas et al 2007). The reduction in 5-HT1A RNA levels in the cortex agrees with pharmacological studies demonstrating that reduced 5-HT signalling delays expression of cortical 5-HT type-1 receptors (Whitaker-Azmitia et al 1996;Lauder et al 2000).…”

Section: Regulation Of Tph2 and 5-ht1a Receptor Expression By Pet-1 Isupporting

confidence: 64%

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Region‐specific regulation of 5‐HT1A receptor expression by Pet‐1‐dependent mechanisms in vivo

Jacobsen

Czesak

Deria

et al. 2011

Journal of Neurochemistry

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J. Neurochem. (2011) 116, 1066–1076. Abstract Serotonin (5‐hydroxytryptamine, 5‐HT) neurotransmission is negatively regulated by 5‐HT1A autoreceptors on raphe neurons, and is implicated in mood disorders. Pet‐1/FEV is an ETS transcription factor expressed exclusively in serotonergic neurons and is essential for serotonergic differentiation, although its regulation of 5‐HT receptors has not yet been studied. Here, we show by electrophoretic mobility shift assay that recombinant human Pet‐1/FEV binds directly to multiple Pet‐1 elements of the human 5‐HT1A receptor promoter to enhance its transcriptional activity. In luciferase reporter assays, mutational analysis indicated that while several sites contribute, the Pet‐1 site at ‐1406 bp had the greatest effect on 5‐HT1A promoter activity. To address the effect of Pet‐1 on 5‐HT1A receptor regulation in vivo, we compared the expression of 5‐HT1A receptor RNA and protein in Pet‐1 null and wild‐type littermate mice. In the raphe nuclei of Pet‐1−/− mice tryptophan hydroxylase 2 (TPH2) RNA, and 5‐HT and TPH immunostaining were greatly reduced, indicating a deficit in 5‐HT production. Raphe 5‐HT1A RNA and protein levels were also reduced in Pet‐1‐deficient mice, consistent with an absence of Pet‐1‐mediated transcriptional enhancement of 5‐HT1A autoreceptors in serotonergic neurons. Interestingly, 5‐HT1A receptor expression was up‐regulated in the hippocampus, but down‐regulated in the striatum and cortex. These data indicate that, in addition to transcriptional regulation by Pet‐1 in raphe neurons, 5‐HT1A receptor expression is regulated indirectly by alterations in 5‐HT neurotransmission in a region‐specific manner that together may contribute to the aggressive/anxiety phenotype observed in Pet‐1 null mice.

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Section: Discussionsupporting

confidence: 60%

Section: Regulation Of Tph2 and 5-ht1a Receptor Expression By Pet-1 Isupporting

confidence: 64%

Region‐specific regulation of 5‐HT1A receptor expression by Pet‐1‐dependent mechanisms in vivo

Jacobsen

Czesak

Deria

et al. 2011

Journal of Neurochemistry

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“…However, the effect of the G/G genotype on postsynaptic 5-HT1A receptors is less clear. The G/G genotype in depressed subjects was associated with no change or increased 5-HT1A receptors in some regions such as the hippocampus (21,22,50), which could reflect a compensatory up-regulation due to lower serotonergic neurotransmission in these subjects (52) or a decrease in forebrain Deaf-1 levels, leading to reduced transcription of the 5-HT1A heteroreceptors (53). Several studies report reduced 5-HT1A RNA or binding in the prefrontal cortex of subjects with major depression (24,(53)(54)(55)(56), consistent with reduced transcription of the 5-HT1A receptor.…”

Section: Altered 5-ht1a Receptor Expression In Deaf-1 Knock-outmentioning

confidence: 93%

Increased Serotonin-1A (5-HT1A) Autoreceptor Expression and Reduced Raphe Serotonin Levels in Deformed Epidermal Autoregulatory Factor-1 (Deaf-1) Gene Knock-out Mice

Czesak

François

Millar

et al. 2012

Journal of Biological Chemistry

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Background: Dysregulation of 5-HT1A receptors is associated with depression, but the transcriptional mechanisms are unclear. Results: Deaf-1 binds the 5-HT1A promoter, and loss of Deaf-1 results in altered expression of 5-HT1A receptors and reduced serotonin levels. Conclusion: Deaf-1 is a key regulator of 5-HT1A expression in vivo that is affected by a promoter polymorphism prevalent in human depression. Significance: Understanding transcriptional regulators of serotonin could lead to improved antidepressant strategies.

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“…Immunohistochemical and in situ hybridization studies have revealed the presence of 5-HT 1A receptor protein and mRNA in external PFC layers in rat (Abbas et al 2007;Kia et al 1996;Pompeiano et al 1992;Santana et al 2004) and in monkey and human brain (Burnet et al 1995;Cruz et al 2004;DeFelipe et al 2001;Marazziti et al 1994;Mengod et al 1996;Pasqualetti et al 1996).…”

Section: Cellular Localization Of 5-ht 1a In Pfcmentioning

confidence: 99%

Distribution of 5-HT and DA receptors in primate prefrontal cortex: implications for pathophysiology and treatment

Almeida

Palacios

Mengod

2008

Progress in Brain Research

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The prefrontal cortex (PFC) has attracted great research interest because of its involvement in the control of executive functions in both health and disease, and particularly in cognitive functions such as working memory. In schizophrenia, alterations in the PFC are documented at many different levels: molecular, cellular and functional. Furthermore, deficits in cognitive abilities are considered a core feature of schizophrenia and remain a major unmet medical need with respect to this disorder. In order to understand the sites of action of currently-used drugs, as well as of the new experimental treatments being developed and acting in this brain region, it is important to have detailed knowledge of the corresponding chemical Fallon et al. 2003). The PFC is described as a six-layered structure, as other neocortical regions, and it is distinguished by a granular layer IV (see Figure 1).In primates the PFC orchestrates thoughts and actions, as well as the planning of complex cognitive and affective functions, and it is therefore implicated in mood disorders (Ebert and Ebmeier 1996). The orbital and medial regions are involved in the control of emotional behavior, whereas the lateral regions, which are highly developed in humans, provide cognitive support to the temporal organization of behavior, speech, reasoning and the execution of complex behaviors that require working memory, as already mentioned; for reviews see (Cavada et al. 2000;Elston 2003;Fuster 1997; Goldman-Rakic et al. 1984).The PFC receives projections from the amygdala (Barbas and de Olmos 1990), the ventral striatum (Kunishio and Haber 1994) and thalamus (Barbas et al. 1991).Specifically, it receives dopaminergic efferents from the ventral tegmental area (VTA) (Berger et al. 1988; Conde et al. 1995;Lindvall et al. 1978) and serotonergic innervation from the median and dorsal raphe nuclei (Berger et al. 1988;Smiley and Goldman-Rakic 1996b), while it sends glutamatergic projections to both the VTA and the nucleus accumbens (Sesack and Pickel 1992;Taber et al. 1995), as well as to the raphe nuclei (Sesack et al. 1989). The PFC is connected with other association cortices but not with primary sensory or motor cortices. There is an important internal network of connectivity between the different divisions of the PFC; indeed, each of the three major prefrontal regions (orbital, medial and lateral) is connected with itself and with the other two. Some of the cortico-cortical connectivity of the PFC is interhemispheric and the majority is organized in a reciprocal and topographical 4 manner (Cavada and Goldman-Rakic 1989a; 1989b). These cortico-cortical connections originate and terminate in upper cortical layers II and III (Andersen et al. 1985).As in other cortical regions, there are two main cell types in the PFC. One is the pyramidal and spiny stellate cells characterized by the excitatory asymmetric synapses which they form (glutamatergic). The majority of cortical neurons are pyramidal output neurons, found mainly in layers II-VI. The othe...

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Antagonist‐induced increase in 5‐HT1A‐receptor expression in adult rat hippocampus and cortex

Cited by 22 publications

References 40 publications

Region‐specific regulation of 5‐HT1A receptor expression by Pet‐1‐dependent mechanisms in vivo

Region‐specific regulation of 5‐HT1A receptor expression by Pet‐1‐dependent mechanisms in vivo

Increased Serotonin-1A (5-HT1A) Autoreceptor Expression and Reduced Raphe Serotonin Levels in Deformed Epidermal Autoregulatory Factor-1 (Deaf-1) Gene Knock-out Mice

Distribution of 5-HT and DA receptors in primate prefrontal cortex: implications for pathophysiology and treatment

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