title: Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation.
abstract: The hippocampal interneurons are very diverse by chemical profiles and rather inconsistent by sensitivity to CI. Some hippocampal GABAergic interneurons survive certain time after ischemia while ischemia-sensitive interneurons and pyramidal neurons are damaged. GABAergic signaling, nicotinic receptors expressing α7-subunit (α7nAChRs(+)) and connexin-36 (Cx36(+), electrotonic gapjunctions protein) contradictory modulate post-ischemic environment. We hypothesized that hippocampal ischemia-resistant GABAergic interneurons coexpressing glutamate decarboxylase-67 isoform (GAD67(+)), α7nAChRs(+), Cx36(+) are able to enhance neuronal viability. To check this hypothesis the histochemical and electrophysiological investigations have been performed using rat hippocampal organotypic culture in the condition of 30-min oxygen-glucose deprivation (OGD). Post-OGD reoxygenation (4h) revealed in CA1 pyramidal layer numerous damaged cells, decreased population spike amplitude and increased pair-pulse depression. In these conditions GAD67(+) interneurons displayed the OGD-resistance and significant increase of GABA synthesis/metabolism (GAD67-immunofluorescence, mitochondrial activity). The α7nAChRs(+) and Cx36(+) co-localizations were revealed in resistant GAD67(+) interneurons. Under OGD: GABAA-receptors (GABAARs) blockade increased cell damage and exacerbated the pair-pulse depression in CA1 pyramidal layer; α7nAChRs and Cx36-channels separate blockades sufficiently decreased cell damage while interneuronal GAD67-immunofluorescence and mitochondrial activity were similar to the control. Thus, hippocampal GABAergic interneurons co-expressing α7nAChRs and Cx36 remained resistant certain time after OGD and were able to modulate CA1 neuron survival through GABAARs, α7nAChRs and Cx36-channels activity. The enhancements of the neuronal viability together with GABA synthesis/metabolism normalization suggest cooperative neuroprotective mechanism that could be used for increase in efficiency of therapeutic strategies against post-ischemic pathology.
authors.affiliation: Department of Cytology, Bogomoletz Institute of Physiology, Kiev, Ukraine. Electronic address: larysa.voytenko@gmail.com.
authors.forename: L P
authors.initials: LP
authors.lastname: Voytenko
authors.affiliation: Department of Cytology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: I V
authors.initials: IV
authors.lastname: Lushnikova
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Ukraine.
authors.forename: A V
authors.initials: AV
authors.lastname: Savotchenko
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Ukraine.
authors.forename: E V
authors.initials: EV
authors.lastname: Isaeva
authors.affiliation: Palladin Institute of Biochemistry, Kiev, Ukraine.
authors.forename: M V
authors.initials: MV
authors.lastname: Skok
authors.affiliation: Palladin Institute of Biochemistry, Kiev, Ukraine.
authors.forename: O Yu
authors.initials: OY
authors.lastname: Lykhmus
authors.affiliation: Department of Cytology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: M A
authors.initials: MA
authors.lastname: Patseva
authors.affiliation: Department of Cytology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: G G
authors.initials: GG
authors.lastname: Skibo
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002229:Carbenoxolone / Q000494:pharmacology; D017630:Connexins / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D000860:Hypoxia / Q000473:pathology; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D015767:Mefloquine / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000097004:Gap Junction delta-2 Protein
chemical_list: D000157:Aconitine; D002229:Carbenoxolone; D017630:Connexins; D018756:GABA Antagonists; D005947:Glucose; D005968:Glutamate Decarboxylase; D015767:Mefloquine; D018733:Nicotinic Antagonists; D011724:Pyridazines; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid; D000097004:Gap Junction delta-2 Protein; C054634:methyllycaconitine; C049853:gabazine; C402565:glutamate decarboxylase 1
keywords: Alpha7-subunit of the nicotinic receptors; Connexin-36; GABAA receptors; GAD67; Neuronal ischemic damage; Neuroprotection