title: Neonatal allopregnanolone or finasteride administration modifies hippocampal K(+) Cl(-) co-transporter expression during early development in male rats.
abstract: The maintenance of levels of endogenous neurosteroids (NS) across early postnatal development of the brain, particularly to the hippocampus, is crucial for their maturation. Allopregnanolone (Allop) is a NS that exerts its effect mainly through the modulation of the GABAA receptor (GABAAR). During early development, GABA, acting through GABAAR, that predominantly produces depolarization shifts to hyperpolarization in mature neurons, around the second postnatal week in rats. Several factors contribute to this change including the progressive increase of the neuron-specific K(+)/Cl(-) co-transporter 2 (KCC2) (a chloride exporter) levels. Thus, we aimed to analyze whether a different profile of NS levels during development is critical and can alter this natural progression of KCC2 stages. We administrated sustained Allop (20mg/kg) or Finasteride (5α-reductase inhibitor, 50mg/kg) from the 5th postnatal day (PD5) to PD9 and assessed changes in the hippocampal expression of KCC2 at transcript and protein levels as well as its active phosphorylated state in male rats. Taken together data indicated that manipulation of NS levels during early development influence KCC2 levels and point out the importance of neonatal NS levels for the hippocampal development.
authors.affiliation: Group of Neurosteroids and Behaviour, Institut de Neurociències, Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mòdol
authors.affiliation: Group of Neuroplasticity and Regeneration, Institut de Neurociències and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 08193 Bellaterra, Barcelona, Spain.
authors.forename: Caty
authors.initials: C
authors.lastname: Casas
authors.affiliation: Group of Neurosteroids and Behaviour, Institut de Neurociències, Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Llidó
authors.affiliation: Group of Neuroplasticity and Regeneration, Institut de Neurociències and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 08193 Bellaterra, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.affiliation: Group of Neurosteroids and Behaviour, Institut de Neurociències, Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallarès
authors.affiliation: Group of Neurosteroids and Behaviour, Institut de Neurociències, Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. Electronic address: sonia.darbra@uab.cat.
authors.forename: Sònia
authors.initials: S
authors.lastname: Darbra
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018120:Finasteride / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011280:Pregnanolone / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D058891:5-alpha Reductase Inhibitors; D000777:Anesthetics; D018120:Finasteride; D011280:Pregnanolone; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D027981:Symporters; D000096922:K Cl- Cotransporters
keywords: Development; GABAA receptor; Hippocampus; Intra cellular chloride; Neurosteroids; Rat