Increased adult hippocampal neurogenesis and abnormal migration of adult‐born granule neurons is associated with hippocampal‐specific cognitive deficits in phospholipase C‐β1 knockout mice

Manning, Elizabeth E.; Ransome, Mark I.; Burrows, Emma L.; Hannan, Anthony J.

doi:10.1002/hipo.20900

Cited by 48 publications

(46 citation statements)

References 71 publications

(100 reference statements)

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“…The integrity of these processes may be crucial for a wide range of sensory and cognitive functions that are impaired in neuropsychiatric diseases (Lewis, 1997). Thus, given the importance of the hippocampus in several psychiatric diseases (Heckers and Konradi, 2010;Tamminga et al, 2010), we wanted to know whether perturbation in a defined adolescent period could affect hippocampal functions in adulthood.…”

Section: Introductionmentioning

confidence: 99%

“…Abnormalities in the hippocampal GABA system, including a significant reduction in the number of interneurons, reduced GABA-receptor (GABAR) expression, and the disinhibition of pyramidal cells, have been implicated in a variety of neuropsychiatric disorders, including deficient sensorimotor processes (Lewis et al, 2004;Heckers and Konradi, 2010). A recent postmortem study has demonstrated developmental changes in the expression of GABA signaling genes in the hippocampus of normal subjects and this progressive pattern of expression is disturbed in schizophrenic patients (Hyde et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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A Sensitive Period for GABAergic Interneurons in the Dentate Gyrus in Modulating Sensorimotor Gating

et al. 2013

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Developmental perturbations during adolescence have been hypothesized to be a risk factor for the onset of several neuropsychiatric diseases. However the physiological alterations that result from such insults are incompletely understood. We investigated whether a defined perturbation during adolescence affected hippocampus-dependent sensorimotor gating functions, a proposed endophenotype in several psychiatric diseases, most notably schizophrenia. The developmental perturbation was induced during adolescence in mice using an antimitotic agent, methylazoxymethanol acetate (MAM), during postnatal weeks (PW) 4 -6. MAM-treated mice showed a decrease in hippocampal neurogenesis immediately after treatment, which was restored by PW10 in adulthood. However, the mice treated with MAM during adolescent stages exhibited a persistent sensorimotor gating deficiency and a reduction in prepulse inhibitionrelated activation of hippocampal and prefrontal neurons in adulthood. Cellular analyses found a reduction of GABAergic inhibitory neurons and abnormal dendritic morphology of immature neurons in the dentate gyrus (DG). Interestingly, bilateral infusion of muscimol, a GABA A receptor agonist, into the DG region reversed the prepulse inhibition abnormality in MAM-treated mice. Furthermore, the behavioral deficits together with the decrease in the number of GABAergic neurons in this MAM model were rescued by exposure to an enriched environment during a defined critical adolescent period. These observations suggest a possible role for GABAergic interneurons in the DG during adolescence. This role may be related to the establishment of neural circuitry required for sensorimotor gating. It is plausible that changes in neurogenesis during this window may affect the survival of GABAergic interneurons, although this link needs to be causally addressed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Sensitive Period for GABAergic Interneurons in the Dentate Gyrus in Modulating Sensorimotor Gating

et al. 2013

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“…Fitzsimons et al (32) showed glucocorticoid receptor knockdown-induced abnormal dendritic complexity, ectopic positioning of newborn granular cells, and impaired memory consolidation for contextual fear conditioning. Phospholipase C-␤1 knock-out mice exhibited abnormal migration of adult-born neurons, and these mice showed a deficit in hippocampal dependent location recognition task (33). Because the mispositioned neurons in these studies also exhibit other morphological defects, it is still unclear whether these memory deficits are attributed by the mispositioning phenotype alone and/or other morphological phenotypes such as dendritic defects.…”

Section: Nrp2-dependent Cell Positioning Of Newborn Neuronsmentioning

confidence: 95%

Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β)

Ng¹,

Hor

Chew³

et al. 2016

Journal of Biological Chemistry

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Edited by Xiao-Fan WangProper positioning of neurons is fundamental for brain functions. However, little is known on how adult-born neurons generated in the hilar side of hippocampal dentate gyrus migrate into the granular cell layer. Because class 3 Semaphorins (Sema3) are involved in dendritic growth of these newborn neurons, we examined whether they are essential for cell positioning. We disrupted Sema3 signaling by silencing neuropilin 1 (NRP1) or 2 (NRP2), the main receptors for Sema3A and Sema3F, in neural progenitors of adult mouse dentate gyrus. Silencing of NRP2, but not NRP1, affected cell positioning of adult newborn neurons. Glycogen synthase kinase-3␤ (GSK3␤) knockdown phenocopied this NRP2 silencing-mediated cell positioning defect, but did not affect dendritic growth. Furthermore, GSK3␤ is activated upon stimulation with Sema3F, and GSK3␤ overexpression rescued the cell positioning phenotypes seen in NRP2-deficient neurons. These results point to a new role for NRP2 in the positioning of neurons during adult hippocampal neurogenesis, acting via the GSK3␤ signaling pathway.

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“…PLCβ1 has been connected with several human diseases such as leukemia [41] and Alzheimer's disease [42] . It is notable that losses of PLCβ1 are found in patients with neurological disorders such as epileptic encephalopathiess and schizophrenia which are recapitulated in Knock-out mice [43,44] . PLCβ1and G protein signaling are linked to gene regulation.…”

Section: Outline Of Plcβ1 Targets and Pathologymentioning

confidence: 99%

Emerging role for PLCβ1 MiRNA and disease

Faenza

Cocco²

2015

RNA Dis

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Nuclear inositides are independently regulated and their regulation is completely independent from the plasma membrane correspondent, hinting that the nucleus represents a specialized distinct compartment of inositol lipids metabolism. This points out that nuclear inositol lipids themselves can influence nuclear key events as transcription and pre-mRNA splicing, growth, proliferation, cell cycle regulation and differentiation. Phospholipase C β1 (PLCβ1) is the most significant enzyme for nuclear inositide signaling. Very recently it has been highlighted that the role of PLCβ1 during erythropoiesis is linked to that of miR-210. Moreover, PLCβ1 signaling is linked to gene regulation and changes in microRNAs (miRNAs) occur with PLCβ1 expression. Molecular targets of PLCβ1 have been found to be important during myogenesis and hematopoiesis. In addition, PLCβ1 signaling has been demonstrated to be impaired in diseases affecting both myogenic differentiation and affecting the hematopoietic system.

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Increased adult hippocampal neurogenesis and abnormal migration of adult‐born granule neurons is associated with hippocampal‐specific cognitive deficits in phospholipase C‐β1 knockout mice

Cited by 48 publications

References 71 publications

A Sensitive Period for GABAergic Interneurons in the Dentate Gyrus in Modulating Sensorimotor Gating

A Sensitive Period for GABAergic Interneurons in the Dentate Gyrus in Modulating Sensorimotor Gating

Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β)

Emerging role for PLCβ1 MiRNA and disease

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