Prem Prakash Tripathi
1*, Yuri Bozzi
21 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, USA
2 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
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.