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[P2.63]: Hyperhomocysteinemia decreases NA + ,K + ‐ atpase activity and glutamate uptake in hippocampus of rats: Prevention of vitamin C
Author(s) -
Machado F.R.,
Ferreira A.G.K.,
Cunha A.A.,
Schimitz F.,
Tagliari B.,
Wyse A.T.S.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.193
Subject(s) - citation , art , library science , computer science
CB1 cannabinoid receptors exert a crucial neuromodulatory role upon engagement by the retrograde agonists anandamide and 2arachidonoylglycerol in different brain areas. In addition, owing to their ability to activate pro-survival signaling mechanisms, CB1 receptors are protective against neuronal degeneration and control neural cell generation and survival. Recent studies have unraveled a previously unknown role of CB1 receptor signalling during cortical development. CB1 receptors regulate pyramidal neuronal specification, together with a role in inhibitory GABAergic interneuron migration and morphogenesis. Thus, CB1 deficient mice at early postnatal stages show aberrant corticofugal connectivity. In the present study we aim to investigate the signaling mechanism by which CB1 receptors participate in pyramidal cell specification and to analyze in detail the different projecting neuronal subtypes regulated by endocannabinoid signaling. Immunofluorescence studies showed reduced cell number of apical and basal progenitors resident in the ventricular zone and subventricular zone of CB1-deficient mouse embryos as compared to wild-type littermates. In agreement, CB1 receptor knockout or electroporated siRNA mediated-CB1 knockdown in wild-type mice, decreased the expression of the pyramidal progenitor markers paired box gene 6 (pax6) and T-box-brain 2 (tbr2, eomes). At more advanced stages and using conditional CB1-deficient mice in the pyramidal lineage (using Nex/Math2-Cre recombinase expression) we analyzed the development of deep and upper cortical neurons with selective layer markers. CB1 receptor knock-out mice show, among others, altered expression of the Tbr2, Tbr1, CTIP2 and SATB2 transcription regulators, and this results in deregulated generation of deep and upper layer cortical neurons. A predominant role of CB1 receptor deficiency in the generation or commitment of layer V neurons is observed, indicating the involvement of CB1 receptors in corticofugal projecting neuronal generation. In summary, our results identify CB1 receptor signalling as critical regulator of the molecular transcription regulatory network involved in the specification of cortical projecting neuron subpopulations.