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The role of dopaminergic and serotonergic systems in neurodevelopmental disorders: a focus on epilepsy and seizure susceptibility.

Tripathi PP, Bozzi Y - Bioimpacts (2015)

Bottom Line: Among these transcription factors, homeobox-containing proteins play a crucial role, and altered expression of these factors can impact the embryonic as well as adult CNS functions.Understanding the embryonic development of these neuronal populations is crucial to elucidate their physiological function including brain excitability in the adult brain.Our results demonstrated that altered development of dopamine (DA) neurons does not interfere with KA seizure susceptibility, while increased serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation leads to resistance to KA-induced seizure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Neuropathology, Center for Integrative Biology (CIBIO), University of Trento, Trento, Italy.

ABSTRACT

Introduction: The embryonic development of the vertebrate Central Nervous System (CNS) requires the induction of transcription factors regulating the expression of specific subsets of genes in restricted CNS regions. Among these transcription factors, homeobox-containing proteins play a crucial role, and altered expression of these factors can impact the embryonic as well as adult CNS functions. Importantly, the homeobox-containing genes Otx2, Engrailed-1 (En1), and Engrailed-2 (En2) have been described to crucially regulate differentiation of dopaminergic and serotonergic neurons during vertebrate CNS development. Dopaminergic and serotonergic neurons, located in midbrain and hindbrain regions respectively, diffusely innervate several forebrain areas including limbic system, contributing in regulating several physiological functions. Understanding the embryonic development of these neuronal populations is crucial to elucidate their physiological function including brain excitability in the adult brain. New evidence is emerging about the impact of an altered embryonic development of dopamine and serotonin neurons onto seizure susceptibility in the adult life.

Methods: In this mini-review, we summarized our kainic acid (KA) induced seizure susceptibility in adult mutant mouse lines with targeted manipulation of Otx2, En1, and En2 genes.

Results: Our results demonstrated that altered development of dopamine (DA) neurons does not interfere with KA seizure susceptibility, while increased serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation leads to resistance to KA-induced seizure.

Conclusion: We propose that developmental alterations of serotonergic but not dopaminergic circuits play a crucial role in controlling seizure susceptibility in the adult life.

No MeSH data available.


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Mentions: We also investigated KA induced seizure susceptibility in En2-/- mice, which showed no alteration in the number of DA and 5-HT neurons at all ages. Surprisingly, En2-/- mice showed increased KA-induced seizures susceptibility. We further investigated the possible reason and consequence for this increased susceptibility, discovering a reduced number of inhibitory interneurons in the hippocampus and cerebral cortex of En2-/- mice.42,43Fig. 2 summarizes KA seizure susceptibility in the different En1/2 and Otx2 mutant mouse strains analyzed in our experiments.


The role of dopaminergic and serotonergic systems in neurodevelopmental disorders: a focus on epilepsy and seizure susceptibility.

Tripathi PP, Bozzi Y - Bioimpacts (2015)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492191&req=5

Mentions: We also investigated KA induced seizure susceptibility in En2-/- mice, which showed no alteration in the number of DA and 5-HT neurons at all ages. Surprisingly, En2-/- mice showed increased KA-induced seizures susceptibility. We further investigated the possible reason and consequence for this increased susceptibility, discovering a reduced number of inhibitory interneurons in the hippocampus and cerebral cortex of En2-/- mice.42,43Fig. 2 summarizes KA seizure susceptibility in the different En1/2 and Otx2 mutant mouse strains analyzed in our experiments.

Bottom Line: Among these transcription factors, homeobox-containing proteins play a crucial role, and altered expression of these factors can impact the embryonic as well as adult CNS functions.Understanding the embryonic development of these neuronal populations is crucial to elucidate their physiological function including brain excitability in the adult brain.Our results demonstrated that altered development of dopamine (DA) neurons does not interfere with KA seizure susceptibility, while increased serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation leads to resistance to KA-induced seizure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Neuropathology, Center for Integrative Biology (CIBIO), University of Trento, Trento, Italy.

ABSTRACT

Introduction: The embryonic development of the vertebrate Central Nervous System (CNS) requires the induction of transcription factors regulating the expression of specific subsets of genes in restricted CNS regions. Among these transcription factors, homeobox-containing proteins play a crucial role, and altered expression of these factors can impact the embryonic as well as adult CNS functions. Importantly, the homeobox-containing genes Otx2, Engrailed-1 (En1), and Engrailed-2 (En2) have been described to crucially regulate differentiation of dopaminergic and serotonergic neurons during vertebrate CNS development. Dopaminergic and serotonergic neurons, located in midbrain and hindbrain regions respectively, diffusely innervate several forebrain areas including limbic system, contributing in regulating several physiological functions. Understanding the embryonic development of these neuronal populations is crucial to elucidate their physiological function including brain excitability in the adult brain. New evidence is emerging about the impact of an altered embryonic development of dopamine and serotonin neurons onto seizure susceptibility in the adult life.

Methods: In this mini-review, we summarized our kainic acid (KA) induced seizure susceptibility in adult mutant mouse lines with targeted manipulation of Otx2, En1, and En2 genes.

Results: Our results demonstrated that altered development of dopamine (DA) neurons does not interfere with KA seizure susceptibility, while increased serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation leads to resistance to KA-induced seizure.

Conclusion: We propose that developmental alterations of serotonergic but not dopaminergic circuits play a crucial role in controlling seizure susceptibility in the adult life.

No MeSH data available.


Related in: MedlinePlus