Neuronal localization of 5-HTIA receptor mRNA and protein in rat embryonic brain stem cultures

Hillion, Joëlle; Catelon, J.; Riad, Mustapha; Hamon, Michel; Vitry, F. De

doi:10.1016/0165-3806(94)90124-4

Cited by 37 publications

(19 citation statements)

References 38 publications

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“…180 5-HT 1A is mainly expressed in the hippocampus and raphe nucleus during embryonic development. 181 Depletion of 5-HT during the early postnatal period leads to the reduction of number and length of dendritic spines in the hippocampus in an 5-HT 1A -dependent fashion. 182 This receptor is also responsible for hippocampal neurogenesis and dendritic maturation in the adult.…”

Section: Autism Candidate Genes and Synaptic Functionmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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Section: Autism Candidate Genes and Synaptic Functionmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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“…However, previously reported antibodies against 5-HT receptors are limited in numbers. These antibodies include anti-peptide rabbit polyclonal antibodies recognizing 5-HT 2A R Morilak et al 1993Morilak et al ,1994, 5-HT 2B R (Choi and Maroteaux 1996), 5-HT 2C R (Abramowski et al 1995;Backstrom et al 1995), 5-HT 1A R (el Mestikawy et al 1990;Azmitia et al 1992;Miquel et al 1992;Matthiessen et al 1993;Raymond et al 1993;Gerard et al 1994;Hillion et al 1994;Sundaram and Strange 1994;Verdot et al 1994Verdot et al ,1995Kia et al 1996a,b), 5-HT 1B R (Grimaldi et al 1995), 5-HT 1D R (Langlois et al 1995), 5-HT 3 R (Kia et al 1995;Morales et al 1996;Mukerji et al 1996), and 5-HT 6 R (Gerard et al 1997) as well as an anti-idiotypic antibody (TH8, generated by immunizing rabbits with affinity-purified antibodies to serotonin) that recognizes 5-HT 1B , 5-HT 2A , and 5-HT 2C receptor subtypes (Tamir et al 1991;Ridet et al 1994). In the present article we have described the development and characterization of an MAb that reacts specifically with the 5-HT 2A receptor.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor

Yoder

Shih

et al. 1998

J Histochem Cytochem.

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SUMMARY Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT 2A receptor. To generate MAbs against 5-HT 2A R, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT 2A R recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT 2A R, rat and human brain lysate, and lysate from cell lines transfected with 5-HT 2A R cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT 2A R N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT 2A R in lysates from rat brain and a 5-HT 2A R-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT 2A R but not with recombinant 5-HT 2B R and 5-HT 2C R. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies. (J Histochem Cytochem 46:811-824, 1998)

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“…For example, 5-HT induces neurogenesis and neuronal differentiation (1-4), affects migration of cranial neural crest cells from the vicinity of the early hindbrain (5), and inhibits growth cone mobility in both mammals and invertebrates (6,7). It has also been shown that 5-HT and many of its receptors are present in the embryo CNS during development (4,(8)(9)(10)(11)(12) In the adult brain, the 5-HT transporter protein (5-HTT) limits the action of 5-HT on its receptors by acting as a sodium-dependent plasma membrane transporter recycling 5-HT into the presynaptic terminal (13). 5-HTT seems to be the major determinant in regulating extracellular 5-HT levels, and as a result, several studies have also suggested that 5-HTT may also play a role in morphogenesis (10,11).…”

mentioning

confidence: 99%

“…Consequently, the association of polymorphic regions to susceptibility to these problems has recently come under scrutiny. Linkage studies of polymorphisms within the 5-HTT gene have indicated that a possible relationship exists between certain polymorphisms and susceptibility to depressive disorders (12,(16)(17)(18)(19)(20)(21)(22)(23)(24). Much interest has focused on a polymorphism within intron 2, which consists of a variable number of tandem repeats (VNTR) containing between 9 (Stin2.9), 10 (Stin2.10), and 12 (Stin2.12) copies of a 17-bp element (16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo

MacKenzie

Quinn

1999

Proc. Natl. Acad. Sci. U.S.A.

339

236

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Polymorphic regions consisting of a variable number of tandem repeats within intron 2 of the gene coding for the serotonin transporter protein 5-HTT have been associated with susceptibility to affective disorders. We have cloned two of these intronic polymorphisms, Stin2.10 and Stin2.12, into an expression vector containing a heterologous minimal promoter and the bacterial LacZ reporter gene. These constructs were then used to produce transgenic mice. In embryonic day 10.5 embryos, both Stin2.10 and Stin2.12 produced consistent ␤-galactosidase expression in the embryonic midbrain, hindbrain, and spinal cord floor plate. However, we observed that the levels of ␤-galactosidase expression produced by both the Stin2.10 and Stin2.12 within the rostral hindbrain differed significantly at embryonic day 10.5. Our data suggest that these polymorphic variable number of tandem repeats regions act as transcriptional regulators and have alleledependent differential enhancer-like properties within an area of the hindbrain where the 5-HTT gene is known to be transcribed at this stage of development.transcriptional regulation ͉ promoter ͉ transgenic mice ͉ LacZ gene ͉ rostral hindbrain

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Neuronal localization of 5-HTIA receptor mRNA and protein in rat embryonic brain stem cultures

Cited by 37 publications

References 38 publications

Advances in behavioral genetics: mouse models of autism

Advances in behavioral genetics: mouse models of autism

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor

A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo

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Neuronal localization of 5-HTIA receptor mRNA and protein in rat embryonic brain stem cultures

Cited by 37 publications

References 38 publications

Advances in behavioral genetics: mouse models of autism

Advances in behavioral genetics: mouse models of autism

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT2AReceptor

A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo

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Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor