Neurogranin Expression Is Regulated by Synaptic Activity and Promotes Synaptogenesis in Cultured Hippocampal Neurons

Garrido-García, Alberto; Andrés, Raquel; Jiménez-Pompa, Amanda; Soriano, Patricia Pérez; Sanz-Fuentes, Diego; Martínez-Blanco, Elena; Díez‐Guerra, F. Javier

doi:10.1007/s12035-019-1593-3

Cited by 16 publications

(20 citation statements)

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“…It involves that the experimental animals can selectively enter into the animal's home cage or secondary exploratory which provide physical exercise, exploration, cognition, and social interaction. It has been demonstrated to strengthen long-term potentiation and augment learning and memory performance [24,25].…”

Section: Introductionmentioning

confidence: 99%

The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus

Guan

Zhao

et al. 2021

Environ Health Prev Med

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Background Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring. Methods Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting. Results There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress’s offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment. Conclusions The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

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Section: Introductionmentioning

confidence: 99%

The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus

Guan

Zhao

et al. 2021

Environ Health Prev Med

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“…Besides, the potentiation of synaptic transmission modulated by Ng mimics and occludes the long-term potentiation ( Zhong et al, 2009 ). A recent study revealed that long-term blockade of NMDAR significantly decreases Ng expression ( Garrido-Garcia et al, 2019 ). Moreover, the long-term bicuculline administration facilitates synaptic activity and increases Ng expression ( Garrido-Garcia et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…A recent study revealed that long-term blockade of NMDAR significantly decreases Ng expression ( Garrido-Garcia et al, 2019 ). Moreover, the long-term bicuculline administration facilitates synaptic activity and increases Ng expression ( Garrido-Garcia et al, 2019 ). Lentiviral expression of Ng results in the elevated density of both excitatory and inhibitory synapses ( Garrido-Garcia et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the long-term bicuculline administration facilitates synaptic activity and increases Ng expression ( Garrido-Garcia et al, 2019 ). Lentiviral expression of Ng results in the elevated density of both excitatory and inhibitory synapses ( Garrido-Garcia et al, 2019 ). In addition, Ng is involved in a variety of biochemical processes and molecular interactions ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Xiang

Xin

Yang³

2020

Front. Aging Neurosci.

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Neurogranin (Ng) is a small protein usually expressed in granule-like structures in pyramidal cells of the hippocampus and cortex. However, its clinical value is not fully clear so far. Currently, Ng is proved to be involved in synaptic plasticity, synaptic regeneration, and long-term potentiation mediated by the calcium- and calmodulin-signaling pathways. Due to both the synaptic integrity and function as the growing concerns in the pathogenesis of a wide variety of neurological and mental diseases, a series of researches published focused on the associations between Ng and these kinds of diseases in the past decade. Therefore, in this review, we highlight several diseases, which include, but are not limited to, Alzheimer’s disease, Parkinson disease, Creutzfeldt–Jakob disease, neuro-HIV, neurosyphilis, schizophrenia, depression, traumatic brain injury, and acute ischemic stroke, and summarize the associations between cerebrospinal fluid or blood-derived Ng with these diseases. We propose that Ng is a potential and promising biomarker to improve the diagnosis, prognosis, and severity evaluation of these diseases in the future.

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“…In contrast, postsynaptic activation raises the local concentration of Ca 2+ , leading to phosphorylation of a serine residue (Ser36) within the IQ motif, rendering the binding to calmodulin impossible [24,25]. Thus, LTP is initiated by transiently Ca 2+ influx inducing Ng dissociation from calmodulin and is essential for establishment of memory and cognition in hippocampal neurons [17,20,26]. In the pre-synapse, synaptotagmin-1 and SNAP-25 are two key players for properly synaptic vesicle exocytosis mediated neurotransmitter release and synaptic activation [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Full-length and C-terminal neurogranin in Alzheimer’s disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays

et al. 2020

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Background Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease. Methods In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and from neurological controls (N = 26). Results The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients (6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001 and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P = 0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC = 0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785). Conclusions Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic integrity of novel drug candidates in clinical trials.

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Neurogranin Expression Is Regulated by Synaptic Activity and Promotes Synaptogenesis in Cultured Hippocampal Neurons

Cited by 16 publications

References 80 publications

The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus

The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Full-length and C-terminal neurogranin in Alzheimer’s disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays

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