Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

Yui, Kunio; Imataka, George; Yoshihara, Shigemi

doi:10.3390/ijms23179803

Cited by 13 publications

(13 citation statements)

References 97 publications

(197 reference statements)

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“…As depicted in the COX‐2KO mouse model (Bosetti et al, 2004; Clemente et al, 2020; Li et al, 2010), many developing genes have differential expression due to the reduced PGE 2 levels. This disrupts synaptic transmission pathways, long‐term nerve potentiation, navigating the neurites, and developing the dendritic spine (Rai‐Bhogal et al, 2018; Yui et al, 2022), consistent with our results.…”

Section: Discussionsupporting

confidence: 92%

The crucial role that hippocampus Cyclooxygenase‐2 plays in memory

Ni,

Guo,

et al. 2023

Eur J of Neuroscience

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It is generally accepted that Cyclooxygenase‐2 (COX‐2) is activated to cause inflammation. However, COX‐2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX‐2 release during neuronal signalling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX‐2 in neuron is still unclear. This research aims to discover the role of COX‐2 in memory beyond neuroinflammation and to determine whether the inhibition of COX‐2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. We found COX‐2 gene knockout (KO) could significantly impact the learning and memory ability, cause neuronal structure disorder and influence gamma oscillations. These might be mediated by the inhibition of prostaglandin (PG) E2/cAMP pathway and phosphorylated protein kinase A (p‐PKA)‐phosphorylated cAMP response element binding protein (p‐CREB)‐brain derived neurotrophic factor (BDNF) axis. It suggested COX‐2 might play a critical role in learning, regulating neuronal structure and gamma oscillations in the hippocampus CA1 by regulating COX‐2/BDNF signalling pathway.

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Section: Discussionsupporting

confidence: 92%

The crucial role that hippocampus Cyclooxygenase‐2 plays in memory

Ni,

Guo,

et al. 2023

Eur J of Neuroscience

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“…By contrast, inhibiting PGE 2 production via local injection of COX-2 inhibitors can decrease dendritic tree arborization and excitatory synaptic density (Dean et al , 2012a). The reduced PGE 2 levels, as seen in COX-2KO mouse model (Bosettiet al , 2004;Li et al , 2010;Clemente et al , 2020), lead to differential expression of many developmental genes, disrupting pathways important for synaptic transmission, long-term potentiation, neurite navigation, and formation of dendritic spines (Rai-Bhogal et al , 2018;Yui et al , 2022) , which is consistence with our results.…”

Section: Discussionsupporting

confidence: 89%

The Crucial Role of Hippocampus Cyclooxygenase-2 Plays in Synaptic Plasticity and Memory

Guo

et al. 2022

Preprint

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It is generally accepted that Cyclooxygenase-2 (COX-2) is activated to cause inflammation. However, COX-2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX-2 release during neuronal signaling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX-2 in neuron is still unclear. This research aims to discover the role of COX-2 in memory beyond neuroinflammation and to determine whether the inhibition of COX-2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. The cognitive ability was assessed by novel object recognition task (NORT) and Morris water maze (MWM) test. Immunofluorescence, Golgi-cox staining were used to observe dendritic synaptic. Gamma oscillation in hippocampus CA1 was performed by Tetrode in-vivo recording. Prostaglandins were measured by HPLC/mass spectrometry. We observed the expressions of cAMP/ BDNF pathway proteins in hippocampus and N2a cells by Elisa and western blot. We found COX-2 gene knockout could significantly impact the learning and memory ability; reduce the expression of PSD95 in the neuron; cause synaptic disorder; influence gamma oscillation and reduce the expression PGE2, cAMP, p-PKA, p-CREB and BDNF in the hippocampus. It suggests COX-2 may play a critical role in learning and memory ability in modulating postsynaptic membrane PSD95, regulating synaptic plasticity and gamma oscillation in the hippocampus CA1 by regulating COX-2/BDNF signaling pathway.

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“…In ASD pathogenesis, lipid metabolism may play an important role [ 66 ], but the molecular mechanisms are poorly defined. Our findings first revealed that ApoA-I is a hub protein with regard to the lipid metabolism in ASD, where aberrantly upregulated ApoA-I has a negative impact on the core phenotypes of ASD.…”

Section: Discussionmentioning

confidence: 99%

Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model

Shi

et al. 2022

IJMS

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Abnormal lipid metabolism has been suggested to contribute to its pathogenesis. Further exploration of its underlying biochemical mechanisms is needed. In a search for reliable biomarkers for the pathophysiology of ASD, hippocampal tissues from the ASD model BTBR T+ Itpr3tf/J (BTBR) mice and C57BL/6J mice were analyzed, using four-dimensional (4D) label-free proteomic analysis and bioinformatics analysis. Differentially expressed proteins were significantly enriched in lipid metabolic pathways. Among them, apolipoprotein A-I (ApoA-I) is a hub protein and its expression was significantly higher in the BTBR mice. The investigation of protein levels (using Western blotting) also confirmed this observation. Furthermore, expressions of SphK2 and S1P in the ApoA-I pathway both increased. Using the SphK inhibitor (SKI-II), ASD core phenotype and phenotype-related protein levels of P-CREB, P-CaMKII, and GAD1 were improved, as shown via behavioral and molecular biology experiments. Moreover, by using SKI-II, we found proteins related to the development and function of neuron synapses, including ERK, caspase-3, Bax, Bcl-2, CDK5 and KCNQ2 in BTBR mice, whose levels were restored to protein levels comparable to those in the controls. Elucidating the possible mechanism of ApoA-I in ASD-associated phenotypes will provide new ideas for studies on the etiology of ASD.

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Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

Cited by 13 publications

References 97 publications

The crucial role that hippocampus Cyclooxygenase‐2 plays in memory

The crucial role that hippocampus Cyclooxygenase‐2 plays in memory

The Crucial Role of Hippocampus Cyclooxygenase-2 Plays in Synaptic Plasticity and Memory

Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model

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