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Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

Popp A, Urbach A, Witte OW, Frahm C - PLoS ONE (2009)

Bottom Line: Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream.Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity.Therefore a functional role in processes like proliferation, migration or synaptogenesis is suggested.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Friedrich-Schiller-University, Jena, Germany.

ABSTRACT

Background: GABA (gamma-aminobutyric acid), the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD). GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods.

Methodology/principal findings: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream.

Conclusions/significance: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or synaptogenesis is suggested.

Show MeSH
Expression of GAD65 and GAD67 in rat cortex (Ctx), hippocampus (HC), cerebellum (Cbl), and olfactory bulb (OB) at different postnatal ages.Probes were examined for GAD transcript expression by qPCR. Numbers of transcripts were calculated per 1000 transcripts of GAPDH. Data represent mean±SEM of five individual animals. #P≤0.05, compared with expression of GAD67 within the same region and at the same postnatal day and as evaluated by Mann-Whitney U test. *P≤0.05, the comparison of regions at each analyzed postnatal day (upper tables) and the comparison of ages within each region (lower tables) as analysed by one-way ANOVA followed by Tukey's post hoc test.
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pone-0004371-g001: Expression of GAD65 and GAD67 in rat cortex (Ctx), hippocampus (HC), cerebellum (Cbl), and olfactory bulb (OB) at different postnatal ages.Probes were examined for GAD transcript expression by qPCR. Numbers of transcripts were calculated per 1000 transcripts of GAPDH. Data represent mean±SEM of five individual animals. #P≤0.05, compared with expression of GAD67 within the same region and at the same postnatal day and as evaluated by Mann-Whitney U test. *P≤0.05, the comparison of regions at each analyzed postnatal day (upper tables) and the comparison of ages within each region (lower tables) as analysed by one-way ANOVA followed by Tukey's post hoc test.

Mentions: GAD65 messages showed a similar expression in cortex, hippocampus, and cerebellum, except of P7 when expression in the hippocampus exceeded that of the cortex. The OB significantly displayed the highest expression of GAD65 from P7 on (Fig. 1). No changes in expression were seen from P1 to P7 and from P21 to P90. Adult levels of GAD65 messages were reached in all regions between P7 and P21 (Fig. 1).


Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

Popp A, Urbach A, Witte OW, Frahm C - PLoS ONE (2009)

Expression of GAD65 and GAD67 in rat cortex (Ctx), hippocampus (HC), cerebellum (Cbl), and olfactory bulb (OB) at different postnatal ages.Probes were examined for GAD transcript expression by qPCR. Numbers of transcripts were calculated per 1000 transcripts of GAPDH. Data represent mean±SEM of five individual animals. #P≤0.05, compared with expression of GAD67 within the same region and at the same postnatal day and as evaluated by Mann-Whitney U test. *P≤0.05, the comparison of regions at each analyzed postnatal day (upper tables) and the comparison of ages within each region (lower tables) as analysed by one-way ANOVA followed by Tukey's post hoc test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2629816&req=5

pone-0004371-g001: Expression of GAD65 and GAD67 in rat cortex (Ctx), hippocampus (HC), cerebellum (Cbl), and olfactory bulb (OB) at different postnatal ages.Probes were examined for GAD transcript expression by qPCR. Numbers of transcripts were calculated per 1000 transcripts of GAPDH. Data represent mean±SEM of five individual animals. #P≤0.05, compared with expression of GAD67 within the same region and at the same postnatal day and as evaluated by Mann-Whitney U test. *P≤0.05, the comparison of regions at each analyzed postnatal day (upper tables) and the comparison of ages within each region (lower tables) as analysed by one-way ANOVA followed by Tukey's post hoc test.
Mentions: GAD65 messages showed a similar expression in cortex, hippocampus, and cerebellum, except of P7 when expression in the hippocampus exceeded that of the cortex. The OB significantly displayed the highest expression of GAD65 from P7 on (Fig. 1). No changes in expression were seen from P1 to P7 and from P21 to P90. Adult levels of GAD65 messages were reached in all regions between P7 and P21 (Fig. 1).

Bottom Line: Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream.Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity.Therefore a functional role in processes like proliferation, migration or synaptogenesis is suggested.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Friedrich-Schiller-University, Jena, Germany.

ABSTRACT

Background: GABA (gamma-aminobutyric acid), the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD). GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods.

Methodology/principal findings: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream.

Conclusions/significance: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or synaptogenesis is suggested.

Show MeSH