IRIS publication 43334425
A Sensitive Period of Mice Inhibitory System to Neonatal GABA Enhancement by Vigabatrin is Brain Region Dependent
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TY - JOUR - Levav-Rabkin, T; Melamed, O; Clarke, G; Farber, M; Cryan, JF; Dinan, TG; Grossman, Y; Golan, HM - 2010 - January - Neuropsychopharmacology - A Sensitive Period of Mice Inhibitory System to Neonatal GABA Enhancement by Vigabatrin is Brain Region Dependent - Validated - () - hippocampus glutamate decarboxylase NKCC1 KCC2 calbindin parvalbumin GLUTAMIC-ACID DECARBOXYLASE CATION-CHLORIDE COTRANSPORTERS THALAMIC RETICULAR NUCLEUS SUBUNIT MESSENGER-RNAS RAT CEREBRAL-CORTEX SYNAPTIC VESICLES NEURODEVELOPMENTAL DISORDERS MYOINOSITOL MONOPHOSPHATASE HIPPOCAMPAL-FORMATION POSTNATAL-DEVELOPMENT - 35 - 1138 - 1154 - Neurodevelopmental disorders, such as schizophrenia and autism, have been associated with disturbances of the GABAergic system in the brain. We examined immediate and long-lasting influences of exposure to the GABA-potentiating drug vigabatrin (GVG) on the GABAergic system in the hippocampus and cerebral cortex, before and during the developmental switch in GABA function (postnatal days P1-7 and P4-14). GVG induced a transient elevation of GABA levels. A feedback response to GABA enhancement was evident by a short-term decrease in glutamate decarboxylase (GAD) 65 and 67 levels. However, the number of GAD65/67-immunoreactive (IR) cells was greater in 2-week-old GVG-treated mice. A long-term increase in GAD65 and GAD67 levels was dependent on brain region and treatment period. Vesicular GABA transporter was insensitive to GVG. The overall effect of GVG on the Cl- co-transporters NKCC1 and KCC2 was an enhancement of their synthesis, which was dependent on the treatment period and brain region studied. In addition, a short-term increase was followed by a long-term decrease in KCC2 oligomerization in the cell membrane of P4-14 hippocampi and cerebral cortices. Analysis of the Ca2+ binding proteins expressed in subpopulations of GABAergic cells, parvalbumin and calbindin, showed region-specific effects of GVG during P4-14 on parvalbumin-IR cell density. Moreover, calbindin levels were elevated in GVG mice compared to controls during this period. Cumulatively, these results suggest a particular susceptibility of the hippocampus to GVG when exposed during days P4-14. In conclusion, our studies have identified modifications of key components in the inhibitory system during a critical developmental period. These findings provide novel insights into the deleterious consequences observed in children following prenatal and neonatal exposure to GABA-potentiating drugs. Neuropsychopharmacology (2010) 35, 1138-1154; doi: 10.1038/npp.2009.219; published online 30 December 2009 - DOI 10.1038/npp.2009.219 DA - 2010/01 ER -
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@article{V43334425, = {Levav-Rabkin, T and Melamed, O and Clarke, G and Farber, M and Cryan, JF and Dinan, TG and Grossman, Y and Golan, HM}, = {2010}, = {January}, = {Neuropsychopharmacology}, = {A Sensitive Period of Mice Inhibitory System to Neonatal GABA Enhancement by Vigabatrin is Brain Region Dependent}, = {Validated}, = {()}, = {hippocampus glutamate decarboxylase NKCC1 KCC2 calbindin parvalbumin GLUTAMIC-ACID DECARBOXYLASE CATION-CHLORIDE COTRANSPORTERS THALAMIC RETICULAR NUCLEUS SUBUNIT MESSENGER-RNAS RAT CEREBRAL-CORTEX SYNAPTIC VESICLES NEURODEVELOPMENTAL DISORDERS MYOINOSITOL MONOPHOSPHATASE HIPPOCAMPAL-FORMATION POSTNATAL-DEVELOPMENT}, = {35}, pages = {1138--1154}, = {{Neurodevelopmental disorders, such as schizophrenia and autism, have been associated with disturbances of the GABAergic system in the brain. We examined immediate and long-lasting influences of exposure to the GABA-potentiating drug vigabatrin (GVG) on the GABAergic system in the hippocampus and cerebral cortex, before and during the developmental switch in GABA function (postnatal days P1-7 and P4-14). GVG induced a transient elevation of GABA levels. A feedback response to GABA enhancement was evident by a short-term decrease in glutamate decarboxylase (GAD) 65 and 67 levels. However, the number of GAD65/67-immunoreactive (IR) cells was greater in 2-week-old GVG-treated mice. A long-term increase in GAD65 and GAD67 levels was dependent on brain region and treatment period. Vesicular GABA transporter was insensitive to GVG. The overall effect of GVG on the Cl- co-transporters NKCC1 and KCC2 was an enhancement of their synthesis, which was dependent on the treatment period and brain region studied. In addition, a short-term increase was followed by a long-term decrease in KCC2 oligomerization in the cell membrane of P4-14 hippocampi and cerebral cortices. Analysis of the Ca2+ binding proteins expressed in subpopulations of GABAergic cells, parvalbumin and calbindin, showed region-specific effects of GVG during P4-14 on parvalbumin-IR cell density. Moreover, calbindin levels were elevated in GVG mice compared to controls during this period. Cumulatively, these results suggest a particular susceptibility of the hippocampus to GVG when exposed during days P4-14. In conclusion, our studies have identified modifications of key components in the inhibitory system during a critical developmental period. These findings provide novel insights into the deleterious consequences observed in children following prenatal and neonatal exposure to GABA-potentiating drugs. Neuropsychopharmacology (2010) 35, 1138-1154; doi: 10.1038/npp.2009.219; published online 30 December 2009}}, = {DOI 10.1038/npp.2009.219}, source = {IRIS} }
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AUTHORS | Levav-Rabkin, T; Melamed, O; Clarke, G; Farber, M; Cryan, JF; Dinan, TG; Grossman, Y; Golan, HM | ||
YEAR | 2010 | ||
MONTH | January | ||
JOURNAL_CODE | Neuropsychopharmacology | ||
TITLE | A Sensitive Period of Mice Inhibitory System to Neonatal GABA Enhancement by Vigabatrin is Brain Region Dependent | ||
STATUS | Validated | ||
TIMES_CITED | () | ||
SEARCH_KEYWORD | hippocampus glutamate decarboxylase NKCC1 KCC2 calbindin parvalbumin GLUTAMIC-ACID DECARBOXYLASE CATION-CHLORIDE COTRANSPORTERS THALAMIC RETICULAR NUCLEUS SUBUNIT MESSENGER-RNAS RAT CEREBRAL-CORTEX SYNAPTIC VESICLES NEURODEVELOPMENTAL DISORDERS MYOINOSITOL MONOPHOSPHATASE HIPPOCAMPAL-FORMATION POSTNATAL-DEVELOPMENT | ||
VOLUME | 35 | ||
ISSUE | |||
START_PAGE | 1138 | ||
END_PAGE | 1154 | ||
ABSTRACT | Neurodevelopmental disorders, such as schizophrenia and autism, have been associated with disturbances of the GABAergic system in the brain. We examined immediate and long-lasting influences of exposure to the GABA-potentiating drug vigabatrin (GVG) on the GABAergic system in the hippocampus and cerebral cortex, before and during the developmental switch in GABA function (postnatal days P1-7 and P4-14). GVG induced a transient elevation of GABA levels. A feedback response to GABA enhancement was evident by a short-term decrease in glutamate decarboxylase (GAD) 65 and 67 levels. However, the number of GAD65/67-immunoreactive (IR) cells was greater in 2-week-old GVG-treated mice. A long-term increase in GAD65 and GAD67 levels was dependent on brain region and treatment period. Vesicular GABA transporter was insensitive to GVG. The overall effect of GVG on the Cl- co-transporters NKCC1 and KCC2 was an enhancement of their synthesis, which was dependent on the treatment period and brain region studied. In addition, a short-term increase was followed by a long-term decrease in KCC2 oligomerization in the cell membrane of P4-14 hippocampi and cerebral cortices. Analysis of the Ca2+ binding proteins expressed in subpopulations of GABAergic cells, parvalbumin and calbindin, showed region-specific effects of GVG during P4-14 on parvalbumin-IR cell density. Moreover, calbindin levels were elevated in GVG mice compared to controls during this period. Cumulatively, these results suggest a particular susceptibility of the hippocampus to GVG when exposed during days P4-14. In conclusion, our studies have identified modifications of key components in the inhibitory system during a critical developmental period. These findings provide novel insights into the deleterious consequences observed in children following prenatal and neonatal exposure to GABA-potentiating drugs. Neuropsychopharmacology (2010) 35, 1138-1154; doi: 10.1038/npp.2009.219; published online 30 December 2009 | ||
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DOI_LINK | DOI 10.1038/npp.2009.219 | ||
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