Early Growth Response 4 Mediates BDNF Induction of Potassium Chloride Cotransporter 2 Transcription

Ludwig, Anastasia; Uvarov, Pavel; Soni, Shetal; Thomas‐Crusells, Judith; Airaksinen, Matti S.; Rivera, Claudio

doi:10.1523/jneurosci.2006-10.2011

Cited by 96 publications

(106 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The encoded protein can act as a homomultimer or as a heteromultimer with other K + -Cl - cotransporters, to maintain Cl - homeostasis in neurons. Increase expression in Slc12a5 correlates with the previous findings of an increased vesicular glutamate transporter Slc17a7 [4] and is pivotal for the maturation of the CNS GABAergic neurotransmission system [45,46]. …”

Section: Discussionsupporting

confidence: 74%

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

Manavalan

Mishra²,

Sze³

et al. 2013

Neurosignals

View full text Add to dashboard Cite

p60 transcription regulator protein (p60TRP) facilitates the processing of the amyloid precursor protein towards the non-amyloidogenic pathway by inhibiting the β-secretase action. This protein was initially identified to be downregulated in the temporal lobe of brains from Alzheimer's disease patients. p60TRP is one of the G-protein-coupled receptor (GPCR)-associated proteins which directly influences the signalling capacity of GPCRs. In the present study, we investigated the brain-region-specific proteome profile of transgenic p60TRP mice to gain an insight into the molecular events mediated by the long-term effect of neuronal p60TRP overexpression on brain proteome changes and its potential implication for neuronal functions in the central nervous system. Using a proteomics research approach based on isobaric tags for relative and absolute quantitation, we identified 2,025 proteins, whereby 1,735 proteins were quantified, out of which 56 were found to be significantly altered in the cortex and/or hippocampus of neuronal transgenic neuronal p60TRP mice. Our data suggests that in vivo overexpression of neuronal p60TRP significantly affects cognitive and neuroprotective capacities.

show abstract

Section: Discussionsupporting

confidence: 74%

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

Manavalan

Mishra²,

Sze³

et al. 2013

Neurosignals

View full text Add to dashboard Cite

show abstract

“…Regulation of KCC2 transcription (Lee et al, 2011; Ludwig et al, 2011; Weishaupt et al, 2012; Yeo et al, 2009), monomer and oligomer formation (Blaesse et al, 2006), functional membrane expression (Lee et al, 2007), the role of BDNF in KCC2 regulation (Boulenguez et al, 2010; Coull et al, 2005) and calpain-mediated degradation (Puskarjov et al, 2012; Zhou et al, 2012) is exceedingly complex. A moderate decrease in membrane oligomeric KCC2 is associated with substantial loss of transporter function (Boulenguez et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury

Jantzie

Getsy

Firl

et al. 2014

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Therapeutic agents that restore the inhibitory actions of γ-amino butyric acid (GABA) by modulating intracellular chloride concentrations will provide novel avenues to treat stroke, chronic pain, epilepsy, autism, neurodegenerative and cognitive disorders. During development upregulation of the potassium-chloride co-transporter KCC2, and the resultant switch from excitatory to inhibitory responses to GABA guides the formation of essential inhibitory circuits. Importantly, maturation of inhibitory mechanisms is also central to the development of excitatory circuits and proper balance between excitatory and inhibitory networks in the developing brain. Loss of KCC2 expression occurs in postmortem samples from human preterm infant brains with white matter lesions. Here we show late gestation brain injury in a rat model of extreme prematurity impairs the developmental upregulation of potassium chloride co-transporters during a critical postnatal period of circuit maturation in CA3 hippocampus by inducing a sustained loss of oligomeric KCC2 via a calpain-dependent mechanism. Further, administration of erythropoietin (EPO) in a clinically relevant postnatal dosing regimen following the prenatal injury protects the developing brain by reducing calpain activity, restoring oligomeric KCC2 expression and attenuating KCC2 fragmentation, thus providing the first report of a safe therapy to address deficits in KCC2 expression. Together, these data indicate it is possible to reverse abnormalities in KCC2 expression during the postnatal period, and potentially reverse deficits in inhibitory circuit formation central to cognitive impairment and epileptogenesis.

show abstract

“…The role of Cdk5-p35 complex in neurogenesis requires ERK activation and induction of zif268 (36). The qualitative change in GABA-mediated responses from depolarizing to hyperpolarizing in adult-born DGCs is related to increased KCC2b expression, which can be directly controlled by stimulating EGR consensus DNA binding sites on KCC2b promoter (37). Finally, the negative regulator REST/ NRSF that controls the rate of adult neurogenesis by partly orchestrating the expression of miR124 and miR132 (38), might regulate transcriptional responses induced by Zif268 expression (39).…”

Section: Discussionmentioning

confidence: 99%

Zif268 / egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning

Veyrac

Gros

Bruel-Jungerman

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

New neurons are continuously added to the dentate gyrus of the adult mammalian brain. During the critical period of a few weeks after birth when newborn neurons progressively mature, a restricted fraction is competitively selected to survive in an experience-dependent manner, a condition for their contribution to memory processes. The mechanisms that control critical stages of experience-dependent functional incorporation of adult newborn neurons remain largely unknown. Here, we identify a unique transcriptional regulator of the functional integration of newborn neurons, the inducible immediate early gene zif268/egr1. We show that newborn neurons in zif268-KO mice undergo accelerated death during the critical period of 2-3 wk around their birth and exhibit deficient neurochemical and morphological maturation, including reduced GluR1 expression, increased NKCC1/KCC2b chloride cotransporter ratio, altered dendritic development, and marked spine growth defect. Investigating responsiveness of newborn neurons to activity-dependent expression of zif268 in learning, we demonstrate that in the absence of zif268, training in a spatial learning task during this critical period fails to recruit newborn neurons and promote their survival, leading to impaired long-term memory. This study reveals a previously unknown mechanism for the control of the selection, functional maturation, and experience-dependent recruitment of dentate gyrus newborn neurons that depends on the inducible immediate early gene zif268, processes that are critical for their contribution to hippocampal-dependent long-term memory. memory consolidation | neurogenesis | plasticity | hippocampus | transcription factor N ew neurons are continuously generated in adult life in discrete regions of the mammalian brain, including in the dentate gyrus (DG) of the hippocampus (1). After birth, the majority of newborn dentate granule cells (DGCs) follow a 2-mo race of development to become fully mature and integrate into existing circuits (2-4), a condition for their contribution to hippocampal functions, in particular to hippocampal-dependent learning and memory and spatial pattern discrimination (5). The cells' involvement as part of neuronal networks supporting learning and memory is believed to be timelocked to a critical stage of maturation (6). From the second week after birth, axons of newborn DGCs elongate (3) and contact hilar and CA3 pyramidal cells (7), then dendrites extend in the molecular layer and spines start to appear (2, 3). Newborn DGCs are initially tonically activated by ambient depolarizing GABA and then hyperpolarized after the gradual conversion of Cl − cotransporter expression (8), along with expression of glutamate receptors and their progressive responsiveness to glutamatergic inputs (8, 9). At this stage, they are hyperexcitable, display properties of enhanced synaptic plasticity, and are prone to integrate the existing hippocampal neurocircuitry (10-12). As their functional maturation progresses, however, newborn DGCs compete to survive, ...

show abstract

Early Growth Response 4 Mediates BDNF Induction of Potassium Chloride Cotransporter 2 Transcription

Cited by 96 publications

References 37 publications

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury

Zif268 / egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning

Contact Info

Product

Resources

About