Schmalbach, Barbara, Lepsveridze, Eka, Djogo, Nevena, Papashvili, Giorgi, Kuang, Fang, Leshchyns'ka, Iryna ORCID: 0000-0002-2025-5831, Sytnyk, Vladimir ORCID: 0000-0003-1927-2199, Nikonenko, Alexander G., Dityatev, Alexander ORCID: 0000-0002-0472-0553, Jakovcevski, Igor ORCID: 0000-0001-7673-9600 and Schachner, Melitta (2015). Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene. J. Neurochem., 135 (4). S. 830 - 845. HOBOKEN: WILEY. ISSN 1471-4159

Full text not available from this repository.

Abstract

In humans, deletions/mutations in the CHL1/CALL gene are associated with mental retardation and schizophrenia. Juvenile CHL1-deficient (CHL1(-/-)) mice have been shown to display abnormally high numbers of parvalbumin-expressing (PV+) hippocampal interneurons and, as adults, display behavioral traits observed in neuropsychiatric disorders. Here, we addressed the question whether inhibitory interneurons and synaptic plasticity in the CHL1(-/-) mouse are affected during brain maturation and in adulthood. We found that hippocampal, but not neocortical, PV+ interneurons were reduced with age in CHL1(-/-) mice, from a surplus of +27% at 1month to a deficit of -20% in adulthood compared with wild-type littermates. This loss occurred during brain maturation, correlating with microgliosis and enhanced interleukin-6 expression. In parallel with the loss of PV+ interneurons, the inhibitory input to adult CA1 pyramidal cells was reduced and a deficit in short- and long-term potentiation developed at CA3-CA1 excitatory synapses between 2 and 9months of age in CHL1(-/-) mice. This deficit could be abrogated by a GABA(A) receptor agonist. We propose that region-specific aberrant GABAergic synaptic connectivity resulting from the mutation and a subsequently enhanced synaptic elimination during brain maturation lead to microgliosis, increase in pro-inflammatory cytokine levels, loss of interneurons, and impaired synaptic plasticity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schmalbach, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lepsveridze, EkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Djogo, NevenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papashvili, GiorgiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuang, FangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leshchyns'ka, IrynaUNSPECIFIEDorcid.org/0000-0002-2025-5831UNSPECIFIED
Sytnyk, VladimirUNSPECIFIEDorcid.org/0000-0003-1927-2199UNSPECIFIED
Nikonenko, Alexander G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dityatev, AlexanderUNSPECIFIEDorcid.org/0000-0002-0472-0553UNSPECIFIED
Jakovcevski, IgorUNSPECIFIEDorcid.org/0000-0001-7673-9600UNSPECIFIED
Schachner, MelittaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-388848
DOI: 10.1111/jnc.13284
Journal or Publication Title: J. Neurochem.
Volume: 135
Number: 4
Page Range: S. 830 - 845
Date: 2015
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1471-4159
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ADHESION MOLECULE L1; GLYCOPROTEIN TENASCIN-R; LONG-TERM POTENTIATION; CLOSE HOMOLOG; EXTRACELLULAR-MATRIX; NEURITE OUTGROWTH; PREFRONTAL CORTEX; PERINEURONAL NETS; PERISOMATIC INHIBITION; GABAERGIC INTERNEURONSMultiple languages
Biochemistry & Molecular Biology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38884

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item