Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats

Kay, Yuni; Tsan, Linda; Davis, Elizabeth A.; Tian, Chen; Décarie-Spain, Léa; Sadybekov, Anastasiia; Pushkin, Anna N.; Katritch, Vsevolod; Kanoski, Scott E.; Herring, Bruce E.

doi:10.1038/s41467-022-28430-5

Cited by 13 publications

(7 citation statements)

References 93 publications

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“…Oxytocin may be critically involved in this function, as knockout of OXTR in the CA2/CA3 region in mice impairs SRM 23 . Here we focused on the dentate gyrus (DG) subregion in the HPCd, a region that has been established as an important center for adult neurogenesis and memory function, particularly for context recognition and other memory tasks involving pattern separation 47, 48, 49, 50 . The ability to distinguish individuals based on various auditory, visual, and olfactory cues is essential for SRM, and can be considered an analogous process to DG-mediated pattern separation.…”

Section: Discussionmentioning

confidence: 99%

Hippocampus oxytocin signaling promotes prosocial eating in rats

Rea,

Liu,

Hayes

et al. 2024

Preprint

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The hypothalamic neuropeptide oxytocin (OT) influences both food intake and social behavior. Given that food preference and consumption are heavily affected by social factors in mammals, it is critical to understand the extent that OT’s role in regulating these two fundamental behaviors is interconnected. Here we evaluated the role of OT signaling in the dentate gyrus of the dorsal hippocampus (HPCd), a brain region recently linked with eating and social memory, on food preference and consumption in rats under conditions that vary with regards to social presence and conspecific familiarity. Results from neuropharmacological and virogenetic knockdown approaches reveal that HPCd OT signaling promotes eating in the presence of a familiar but not an unfamiliar conspecific. Additionally, HPCd OT receptor signaling is required for the social transmission of food preference. These findings collectively identify the HPCd as a novel substrate where oxytocin synergistically influences eating and social behaviors.

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Section: Discussionmentioning

confidence: 99%

Hippocampus oxytocin signaling promotes prosocial eating in rats

Rea,

Liu,

Hayes

et al. 2024

Preprint

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“…As previously described, we use open field test measures hyperactivity through locomotion and anxious behavior [ 24 ]. The apparatus was a black plastic open arena without any bedding (40 cm × 40 cm × 30 cm, L × W × H), which was placed under diffuse even lighting (30 lx).…”

Section: Methodsmentioning

confidence: 99%

Investigating the molecular mechanisms of delirium-like neuropsychiatric disorder induced by electromagnetic pulse based on bioinformatics analysis

Zhang

Xiao

et al. 2023

Mol Brain

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Electromagnetic pulse (EMP), a unique type of electromagnetic radiation, may induce diverse neuropsychiatric disorders, such as irritability, hyperkinesis, retardation of learning and memory. However, the underlying mechanism of EMP exposure on neuronal injury has not been elucidated. Here, we aimed to delineate the regulatory expression networks based on high-throughput sequencing data to explore the possible molecular mechanisms related to EMP-induced delirium-like neuropsychiatric disorder in rats. It’s shown that EMP exposure induced anxiety, cognitive decline and short-term memory impairment. The expression profiles of the long noncoding RNAs (lncRNAs) and mRNAs, along with their biological function and regulatory network, were explored in rats after EMP exposure. We identified 41 differentially expressed lncRNAs (DELs) and 266 differentially expressed mRNAs (DEMs) between EMP and sham groups. Sixty-one co-expression relationships between 18 DELs and 56 DEMs were mostly associated with synapse- and metabolic-related pathways. We predicted 51 DEL-miRNA pairs and 290 miRNA-mRNA pairs using the miRanda database to constructed a DEL-miRNA-DEM network. LncRNA AABR07042999.1 and mRNA Tph2, Slc6a4, Dbh and Th were upregulated, and the contents of serotonin, dopamine and norepinephrine were increased in both PFC and HIP after EMP exposure. The current study provided a better understanding of the ceRNA network, which might reveal the pathological mechanism and provide more treatment options for the EMP-induced neurobehavioral disorder.

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“…Both the ANK2 and ANK3 genes show strong associations with SZ ( Luoni et al, 2016 ; Stevens and Rasband, 2021 ). Second, NrCAM is also associated with SAP97 ( Dirks et al, 2006 ), an adapter for glutamate receptors ( Waites et al, 2009 ; Li et al, 2011 ); SAP97 is associated with SZ, in particular with neurocognitive dysfunctions ( Uezato et al, 2017 ; Xu et al, 2018 , 2020 , 2021 ), and SZ-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory ( Kay et al, 2022 ). Third, NrCAM is expressed in cortical astrocytes and neurons and forms perisynaptic contacts at inhibitory synapses.…”

Section: Introductionmentioning

confidence: 99%

NrCAM-deficient mice exposed to chronic stress exhibit disrupted latent inhibition, a hallmark of schizophrenia

Buhusi,

Brown,

Buhusi

2024

Front. Behav. Neurosci.

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The neuronal cell adhesion molecule (NrCAM) is widely expressed and has important physiological functions in the nervous system across the lifespan, from axonal growth and guidance to spine and synaptic pruning, to organization of proteins at the nodes of Ranvier. NrCAM lies at the core of a functional protein network where multiple targets (including NrCAM itself) have been associated with schizophrenia. Here we investigated the effects of chronic unpredictable stress on latent inhibition, a measure of selective attention and learning which shows alterations in schizophrenia, in NrCAM knockout (KO) mice and their wild-type littermate controls (WT). Under baseline experimental conditions both NrCAM KO and WT mice expressed robust latent inhibition (p = 0.001). However, following chronic unpredictable stress, WT mice (p = 0.002), but not NrCAM KO mice (F < 1), expressed latent inhibition. Analyses of neuronal activation (c-Fos positive counts) in key brain regions relevant to latent inhibition indicated four types of effects: a single hit by genotype in IL cortex (p = 0.0001), a single hit by stress in Acb-shell (p = 0.031), a dual hit stress x genotype in mOFC (p = 0.008), vOFC (p = 0.020), and Acb-core (p = 0.032), and no effect in PrL cortex (p > 0.141). These results indicating a pattern of differential effects of genotype and stress support a complex stress × genotype interaction model and a role for NrCAM in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders.

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Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats

Cited by 13 publications

References 93 publications

Hippocampus oxytocin signaling promotes prosocial eating in rats

Hippocampus oxytocin signaling promotes prosocial eating in rats

Investigating the molecular mechanisms of delirium-like neuropsychiatric disorder induced by electromagnetic pulse based on bioinformatics analysis

NrCAM-deficient mice exposed to chronic stress exhibit disrupted latent inhibition, a hallmark of schizophrenia

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