NKCC1 and KCC2 protein expression is sexually dimorphic in the hippocampus and entorhinal cortex of neonatal rats

Murguía-Castillo, Justo; Beas‐Zárate, Carlos; Rivera-Cervantes, M.C.; Feria‐Velasco, Alfredo; Ureña‐Guerrero, Mónica E.

doi:10.1016/j.neulet.2013.07.038

Cited by 36 publications

(46 citation statements)

References 24 publications

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“…Recently, it was reported that NLGN2 expression precedes and regulates KCC2 expression (Sun et al, ), the transporter responsible for GABA‐induced chloride currents in vitro (Ben‐Ari, ; Rivera et al, ) and the transition from excitatory GABAergic function to adult inhibitory function (Cancedda et al, ). Typically, NKCC1 expression levels decrease in the second week (Leinekugel et al, ; Murguia‐Castillo et al, ; Yamada et al, ; see Fig. ), whereas KCC2 expression levels increase through the second and third weeks of life before reaching adult levels (Leinekugel et al, ; Takayama and Inoue, ; Yamada et al, ).…”

Section: Discussionmentioning

confidence: 99%

Developmental expression of the neuroligins and neurexins in fragile X mice

Lai

Doering

Foster

2015

J of Comparative Neurology

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Neuroligins and neurexins are transsynaptic proteins involved in the maturation of glutamatergic and GABAergic synapses. Research has identified synaptic proteins and function as primary contributors to the development of fragile X syndrome. Fragile X mental retardation protein (FMRP), the protein that is lacking in fragile X syndrome, binds neuroligin-1 and -3 mRNA. Using in situ hybridization, we examined temporal and spatial expression patterns of neuroligin (NLGN) and neurexin (NRXN) mRNAs in the somatosensory (S1) cortex and hippocampus in wild-type (WT) and fragile X knockout (FMR1-KO) mice during the first 5 weeks of postnatal life. Genotype-based differences in expression included increased NLGN1 mRNA in CA1 and S1 cortex, decreased NLGN2 mRNA in CA1 and dentate gyrus (DG) regions of the hippocampus, and increased NRXN3 mRNA in CA1, DG, and S1 cortex between female WT and FMR1-KO mice. In male mice, decreased expression of NRXN3 mRNA was observed in CA1 and DG regions of FMR1-KO mice. Sex differences in hippocampal expression of NLGN2, NRXN1, NRXN2, and NRXN3 mRNAs and in S1 cortex expression of NRXN3 mRNAs were observed WT mice, whereas sex differences in NLGN3, NRXN1, NRXN2, and NRXN3 mRNA expression in the hippocampus and in NLGN1, NRXN2 and NRXN3 mRNA expression in S1 cortex were detected in FMR1-KO mice. These results provide a neuroanatomical map of NLGN and NRXN expression patterns over postnatal development in WT and FMR1-KO mice. The differences in developmental trajectory of these synaptic proteins could contribute to long-term differences in CNS wiring and synaptic function.

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Section: Discussionmentioning

confidence: 99%

Developmental expression of the neuroligins and neurexins in fragile X mice

Lai

Doering

Foster

2015

J of Comparative Neurology

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“…Two major cation‐chloride cotransporters at the neurons should be noted: NKCC1, an importer of Na + /K + /Cl − , and KCC2, an exporter of K + /Cl − . NKCC1 is highly expressed in immature neurons, whereas KCC2 is expressed at low levels, and the opposite is observed in adult neurons (Dzhala et al, ; Li & Xu, ; Murguía‐Castillo, Beas‐Zárate, Rivera‐Cervantes, Feria‐Velasco, & Ureña‐Guerrero, ). This condition contributes to a higher concentration of intracellular Cl − than extracellular Cl − in the early developmental stages.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABA_AR α1/GABA_AR α2 ratio

Xie

et al. 2017

J of Neuroscience Research

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Exposure of neonatal rat to sevoflurane leads to neurodegeneration and deficits of spatial learning and memory in adulthood. However, the underlying mechanisms remain unclear. The type A γ-aminobutyric acid receptor (GABA R) is a target receptor for sevoflurane. The present study intends to investigate the changes in GABA R α1/α2 expression and its relationship with the neurotoxicity effect due to sevoflurane in neonatal rats. After a dose-response curve was constructed to determine minimum alveolar concentration (MAC) and safety was guaranteed in our 7-day-old neonatal rat pup mode, we conducted two studies among the following groups: (A) the control group; (B) the sham anesthesia group; and (C) the sevoflurane anesthesia group and all three groups were treated in the same way as the model. First, poly(ADP-ribose) polymerase-1 protein (PARP-1) expression was determined in the different brain areas at 6 hr after anesthesia. Second, the expression of PARP-1 and GABA R α1/GABA R α2 in the hippocampus area was tested by Western blotting at 6 hr, 24 hr, and 72 hr after anesthesia in all three groups. After 4 hr, with 0.8 MAC (2.1%) sevoflurane anesthesia, the PARP-1 expression was significantly higher in the hippocampus than the other brain areas (p < .05). Compared with Groups A and B, the expression of PARP-1 in the hippocampus of Group C significantly increased at 6 hr after sevoflurane exposure (216% ± 15%, p < .05), and the ratio of the α1/α2 subunit of GABA R surged at 6 hr (126% ± 6%), 24 hr (127% ± 8%), and 72 hr (183% ± 22%) after sevoflurane exposure in the hippocampus (p < .05). Our study showed that sevoflurane exposure of 0.8 MAC (2.1%)/4 hr was a suitable model for 7-day-old rats. And the exposure to sevoflurane could induce the apoptosis of neurons in the early stage, which may be related to the transmission from GABA R α2 to GABA R α1.

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“…Previous research has revealed that NKCC1 expression was different in the neurons of neonatal rat thalamus and neocortex (71). The EC and CA3 of the neonatal rat also showed different NKCC1 expression levels (10, 19); moreover, GABAergic action was different when compared between the ventroposterior thalamus and neocortex during the early development period (9). This implies that GABAergic excitation resulting from NKCC1 is unequal in different brain regions in the neonatal period.…”

Section: Discussionmentioning

confidence: 99%

“…Their animal age were not identical with our animals, and they also did not distinguish the animal gender. Previous research has showed that NKCC1 expression was region- and age-dependent (10), and it is also sexually dimorphic in the hippocampus of neonatal rats: in males, NKCC1 expression was constant during the first week, peaking almost three-fold higher than the initial level at P9, and the level of NKCC1 was higher at P8–P10 than that at P4–P7 in the hippocampus; while in the females, NKCC1 expression was constant during P1–P15 (19). Bumetanide is the blocker of NKCC1, therefore, its antiepileptic action was related to the level of NKCC1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Some experiments have indicated that bumetanide, a blocker of NKCC1, abolishes IDs and depresses IIDs in the neonatal CA3 (11). However, NKCC1 expression is age and region dependent (10, 19). If the neonatal subiculum was able to initiate epileptiform discharges (IDs and IIDs) independently, it is uncertain whether these epileptiform discharges also result from the GABAergic excitation caused by NKCC1.…”

Section: Introductionmentioning

confidence: 99%

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The Subiculum: A Potential Site of Ictogenesis in a Neonatal Seizure Model

Wang

Gong

et al. 2017

Front. Neurol.

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Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg2+ or high-K+ artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed. The Na+–K+–2Cl− cotransporter 1 (NKCC1) blocker, bumetanide, was applied to test its effect upon epileptiform discharges in low-Mg2+ model. The effect of N-methyl-d-aspartate receptors (NMDARs) antagonist, d-AP5, upon the epileptiform discharges in high-K+ model was examined. We found that the neonatal subiculum not only relayed epileptiform discharges emanating from the hippocampus proper (HP) but also initiated epileptiform discharges (interictal- and ictal-like discharges) independently. The latency to onset of the first epileptiform discharge initiated in the subiculum was similar to that initiated in the HP. Bumetanide efficiently blocked seizures in the neonatal HP, but was less effectively in suppressing seizures initiated in the subiculum. In high-K+ model, d-AP5 was more effective in blocking seizures initiated in the subiculum than that initiated in the HP. Furthermore, Western blotting analysis showed that NKCC1 expression was lower in the subiculum than that in the HP, whereas the expression of NMDAR subunits, NR2A and NR2B, was higher in the subiculum than that in the HP. Our results revealed that the subiculum was a potential site of ictogenesis in neonatal seizures and possessed similar seizure susceptibility to the HP. GABAergic excitation resulting from NKCC1 may play a less dominant role during ictogenesis in the subiculum than that in the HP. The subicular ictogenesis may be related to the glutamatergic excitation mediated by NMDARs.

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NKCC1 and KCC2 protein expression is sexually dimorphic in the hippocampus and entorhinal cortex of neonatal rats

Cited by 36 publications

References 24 publications

Developmental expression of the neuroligins and neurexins in fragile X mice

Developmental expression of the neuroligins and neurexins in fragile X mice

Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABA_AR α1/GABA_AR α2 ratio

The Subiculum: A Potential Site of Ictogenesis in a Neonatal Seizure Model

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NKCC1 and KCC2 protein expression is sexually dimorphic in the hippocampus and entorhinal cortex of neonatal rats

Cited by 36 publications

References 24 publications

Developmental expression of the neuroligins and neurexins in fragile X mice

Developmental expression of the neuroligins and neurexins in fragile X mice

Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABAAR α1/GABAAR α2 ratio

The Subiculum: A Potential Site of Ictogenesis in a Neonatal Seizure Model

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Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABA_AR α1/GABA_AR α2 ratio