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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

ABSTRACT: We demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE180598 | GEO | 2022/02/02

REPOSITORIES: GEO

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:We demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders.

2022-02-02 | GSE158606 | GEO

Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner.

Project description: Not available

| S-EPMC8782590 | biostudies-literature

Targeting Pyk2 inhibition enhances bone restoration

Project description:Understanding the intricate cellular interactions involved in bone restoration is crucial for developing effective strategies to promote bone healing and mitigate conditions such as osteoporosis and fractures. Here, we provide compelling evidence supporting the anabolic effects of a pharmacological Pyk2 inhibitor (Pyk2-Inh) in promoting bone restoration. Using an ovariectomized mouse model, we administered Pyk2-Inh orally, resulting in increased bone mass characterized by reduced bone resorption, increased bone formation and decreased bone marrow fat. In vitro, Pyk2 inhibition significantly impedes osteoclast differentiation and bone resorption. In a co-culture system comprising osteoblasts and osteoclasts, Pyk2-Inh effectively suppressed osteoclast differentiation, accompanied by a substantial increase in the transcriptional expression of Tnfrsf11b and Csf1 in osteoblasts. Additionally, Pyk2 signaling inhibition markedly enhances alkaline phosphatase (ALP) activity, a hallmark of osteoblast differentiation, through an increase in canonical Wnt/β-catenin signaling. Notably, analysis of human mesenchymal stem cells through RNA-seq revealed a novel candidate, SCARA5, identified through Pyk2-Inh treatment. We demonstrate that Scara5 plays a crucial role in suppressing the differentiation from stromal cell into adipocytes, and accelerates lineage commitment to osteoblasts, establishing Scara5 as a negative regulator of bone formation. These results suggest Pyk2 as a potential therapeutic target for both adipogenesis and osteogenesis in bone marrow. Our findings underscore the importance of Pyk2 signaling inhibition as a key regulator of bone remodeling, offering promising prospects for the development of novel osteoporosis therapies.

2024-11-27 | GSE266328 | GEO

Sono-Seq analysis of contextual fear conditioning

Project description:This dataset constitutes the first Sono-Seq study of chromatin accessibility following contextual fear conditioning in the mouse hippocampus.

2017-11-20 | GSE98317 | GEO

RNA-seq analysis of contextual fear conditioning

Project description:This dataset constitutes the first RNA-seq study of gene expression following contextual fear conditioning in the mouse hippocampus.

2015-07-22 | GSE63412 | GEO

Encoding of Contextual Fear Memory Requires De Novo Proteins in the Prelimbic Cortex

Project description:Time dependent coordinated hippocampal-prefrontal cortical interactions are required for the long-term storage of memories. However, the role of prefrontal cortex (PFC) in encoding of long-term memories remains elusive. Here, we discover a critical role of PFC in the encoding of contextual memories in mice. We demonstrate that specific pools of mRNAs are translated in the PFC following one and six hours of behavioral training. Moreover, disruption of protein synthesis in the prelimbic region of PFC immediately after training inhibits encoding contextual fear memories, whereas disruption at six hours after training is ineffective. Thus, early protein synthesis in the PFC is necessary and critical for the encoding of contextual fear memories. These findings establish key role for the prelimbic cortex in encoding of contextual memories.

2017-01-06 | GSE61529 | GEO

Gene expression in rat hippocampal CA1 during the extinction of contextual fear memory

Project description:Adult rats (male Lister hooded) were pre-exposed for 3 d for 10 min /d (24 hr interval) to two different novel contexts. On day 4 rats received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to one of the two contexts. Rats were either returned to the CS conditioned context (CS+, EXT group) or to the other (CS-, NOR group) context for 10 min, 48h after contextual fear conditioning. Rats were housed in the home cages at all times outside the conditioning and re-exposure components. The novel context chosen to be the conditioned context was counterbalanced across the experimental groups. Rats were killed by CO2 inhalation 2 hours after CS- or CS+ exposure. CA1-enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The CS+ group represents rats that underwent extinction of contextual fear memory.

2015-09-25 | GSE66151 | GEO

Strain differences in responsiveness to chronic restraint stress affect remote contextual fear memory and blood transcriptomics

Project description:Fear memory regulation is thought to be similar between humans and animals, and the role of stress in altering remote memory is little explored. Since individual variation in stress reactivity exists, should stress alter remote memory, invividuals with differing stress-reactivity would affect it to various degree. We evaluate this question using two strains of rats with differing stress-reactivity. The Fisher 344 (F344) strain is known to have active coping style and represent normal stress-reactivity, while the Wistar–Kyoto (WKY) rat shows passive coping strategies and heightened stress-reactivity. Male animals were exposed contextual fear conditioning (CFC) and four weeks later, chronic restraint stress (CRS) or no stress (NS) was administered for two weeks. Remote memory, immediate stress response to a second CFC, and reinstated fear memory was measured. Both recent and reinstated fear memory were greater in F344s, regardless of the stress status, In contrast, remote memory was attenuated in F344 only, concurring with their increased immediate stress responsive behavior after CRS. To find if this strain-specific response to CRS can be mirrored by transcriptomic changes in the blood, RNA sequencing was carried out. Overlapping differentially expressed genes (DEGs) between NS vs. CRS in the blood of F344 and WKY suggest a convergence of stress-related molecular mechanisms, independent of stress-reactivity. In contrast, DEGs unique to the F344 and the WKY stress responses are divergent in their functionality and networks, beyond that of strain differences in their non-stressed state. These unique DEGs than could be implicated as biomarkers stress-reactivity.

2020-10-01 | GSE148151 | GEO

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