Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene.
Standard
Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene. / Schmalbach, Barbara ; Lepsveridze, Eka; Djogo, Nevena; Papashvili, Giorgi ; Kuang, Fang; Leshchyns´ka, Iryna; Sytnyk, Vladimir; Nikonenko, Alexander; Dityatev, Alexander; Jakovcevski, Igor; Schachner, Melitta.
In: J NEUROCHEM, Vol. 135, No. 4, 08.09.2015, p. 830-844.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene.
AU - Schmalbach, Barbara
AU - Lepsveridze, Eka
AU - Djogo, Nevena
AU - Papashvili, Giorgi
AU - Kuang, Fang
AU - Leshchyns´ka, Iryna
AU - Sytnyk, Vladimir
AU - Nikonenko, Alexander
AU - Dityatev, Alexander
AU - Jakovcevski, Igor
AU - Schachner, Melitta
PY - 2015/9/8
Y1 - 2015/9/8
N2 - 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 1 month 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 9 months of age in CHL1(-/-) mice. This deficit could be abrogated by a GABAA 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. Close homolog of L1-deficient (CHL1(-/-) ) mice have abnormally high numbers of parvalbumin (PV)-expressing hippocampal interneurons in juvenile animals, but in adult animals a loss of these cells is observed. This loss correlates with an increased density of microglia (M), enhanced interleukin-6 (IL6) production and a deficit in short- and long-term potentiation at CA3-CA1 excitatory synapses. Furthermore, adult CHL1(-/-) mice display behavioral traits similar to those observed in neuropsychiatric disorders of humans.
AB - 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 1 month 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 9 months of age in CHL1(-/-) mice. This deficit could be abrogated by a GABAA 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. Close homolog of L1-deficient (CHL1(-/-) ) mice have abnormally high numbers of parvalbumin (PV)-expressing hippocampal interneurons in juvenile animals, but in adult animals a loss of these cells is observed. This loss correlates with an increased density of microglia (M), enhanced interleukin-6 (IL6) production and a deficit in short- and long-term potentiation at CA3-CA1 excitatory synapses. Furthermore, adult CHL1(-/-) mice display behavioral traits similar to those observed in neuropsychiatric disorders of humans.
M3 - SCORING: Journal article
VL - 135
SP - 830
EP - 844
JO - J NEUROCHEM
JF - J NEUROCHEM
SN - 0022-3042
IS - 4
ER -