A novel knockout mouse model of the noncoding antisense Brain-Derived Neurotrophic Factor (Bdnf) gene displays increased endogenous Bdnf protein and improved memory function following exercise

Modarresi, Farzaneh; Fatemi, Roya Pedram; Razavipour, Seyedeh Fatemeh; Ricciardi, Natalie; Makhmutova, Madina; Khoury, Nathalie; Magistri, Marco; Volmar, Claude‐Henry; Wahlestedt, Claes; Faghihi, Mohammad Ali

doi:10.1016/j.heliyon.2021.e07570

Cited by 5 publications

(1 citation statement)

References 49 publications

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“…The copyright holder for this preprint (which this version posted May 26, 2024. ; https://doi.org/10.1101/2024.05.25.595903 doi: bioRxiv preprint Despite significant advancements, genetic evidence validating the in vivo functions of many long non-coding RNAs (lncRNAs) remains limited. Recent studies have begun to address this gap by generating genetically modified animals with either loss or gain of function in specific lncRNAs (Mattick, 2013;Sauvageau et al, 2013;Ip et al, 2016;Modarresi et al, 2021). Given the large number of expressed lncRNAs, it is urgent to elucidate their functional roles through genetic analyses, especially considering their implications in neurobiological processes such as structural changes, synaptic transmission, transcriptional regulation, and complex behaviors like drug addiction and memory formation.…”

Section: Introductionmentioning

confidence: 99%

lncRNA ADEPTR loss-of-function elicits sex-specific behavioral and spine deficits

Chanda,

Carter,

Nishizono

et al. 2024

Preprint

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Activity dependent changes in neuronal connections are fundamental to learning and long-term memory storage. However, the precise contribution of long noncoding RNAs (lncRNAs) to these modifications remains unclear. In this study, we assessed the role of the lncRNA ADEPTR, a cAMP modulated lncRNA localized in dendrites, which is crucial for synapse morphology. By generating two different mouse models, one with a deletion of ADEPTR (LADEPTR) and one with a deletion of its protein interaction region (SADEPTR) we investigated the sex specific impacts of ADEPTR loss of function on learning, memory, dendritic arborization, and synapse morphology. Our behavioral analyses revealed a reduction in anxiety in adult male mice, while learning and memory remained unaffected in both models. Systematic evaluations of neuronal morphology across various developmental stages (~3 day old postnatal neuronal cultures and postnatal 14 and 42 day old male and female mice) uncovered substantial deficits in neuronal architecture in both S and L ADEPTR male and female neuronal cultures. At postnatal day 42, in contrast to their male counterparts, L ADEPTR female mice exhibited a significant deficiency in thin spines. Additionally, we found that the expression of plasticity related gene BDNF, and immediate early gene cFOS were enhanced in both the cortex and hippocampus of adult male and female S and L ADEPTR mice, suggesting the activation of a compensatory mechanism protecting against learning and memory deficits. Collectively, these observations underscore the sex specific role of lncRNA ADEPTR in shaping neuronal morphology and anxiety behavior.

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Section: Introductionmentioning

confidence: 99%

lncRNA ADEPTR loss-of-function elicits sex-specific behavioral and spine deficits

Chanda,

Carter,

Nishizono

et al. 2024

Preprint

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Synaptic Mechanisms of Delay Eyeblink Classical Conditioning: AMPAR Trafficking and Gene Regulation in an In Vitro Model

Keifer

2023

Mol Neurobiol

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Mitragynine inhibits hippocampus neuroplasticity and its molecular mechanism

Yunusa,

Hassan,

Müller

2023

Pharmacol. Rep

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Background Mitragynine (MIT), the primary indole alkaloid of kratom (Mitragyna speciosa), has been associated with addictive and cognitive decline potentials. In acute studies, MIT decreases spatial memory and inhibits hippocampal synaptic transmission in long-term potentiation (LTP). This study investigated the impacts of 14-day MIT treatment on hippocampus synaptic transmission and its possible underlying mechanisms. Methods Under urethane anesthesia, field excitatory post-synaptic potentials (fEPSP) of the hippocampal CA1 region were recorded in the Sprague Dawley (SD) rats that received MIT (1, 5, and 10 mg/kg), morphine (MOR) 5 mg/kg, or vehicle (ip). The effects of the treatments on basal synaptic transmission, paired-pulse facilitation (PPF), and LTP were assessed in the CA1 region. Analysis of the brain's protein expression linked to neuroplasticity was then performed using a western blot. Results The baseline synaptic transmission's amplitude was drastically decreased by MIT at 5 and 10 mg/kg doses, although the PPF ratio before TBS remained unchanged, the PPF ratio after TBS was significantly reduced by MIT (10 mg/kg). Strong and persistent inhibition of LTP was generated in the CA1 region by MIT (5 and 10 mg/kg) doses; this effect was not seen in MIT (1 mg/kg) treated rats. In contrast to MIT (1 mg/kg), MIT (5 and 10 mg/kg) significantly raised the extracellular glutamate levels. After exposure to MIT, GluR-1 receptor expression remained unaltered. However, NMDAε2 receptor expression was markedly downregulated. The expression of pCaMKII, pERK, pCREB, BDNF, synaptophysin, PSD-95, Delta fosB, and CDK-5 was significantly downregulated in response to MIT (5 and 10 mg/kg) exposure, while MOR (5 mg/kg) significantly raised synaptophysin and Delta fosB expression. Conclusion Findings from this work reveal that a smaller dose of MIT (1 mg/kg) poses no risk to hippocampal synaptic transmission. Alteration in neuroplasticity-associated proteins may be a molecular mechanism for MIT (5 and 10 mg/kg)-induced LTP disruption and cognitive impairments. Data from this work posit that MIT acted differently from MOR on neuroplasticity and its underlying mechanisms. Graphical abstract

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A novel knockout mouse model of the noncoding antisense Brain-Derived Neurotrophic Factor (Bdnf) gene displays increased endogenous Bdnf protein and improved memory function following exercise

Cited by 5 publications

References 49 publications

lncRNA ADEPTR loss-of-function elicits sex-specific behavioral and spine deficits

lncRNA ADEPTR loss-of-function elicits sex-specific behavioral and spine deficits

Synaptic Mechanisms of Delay Eyeblink Classical Conditioning: AMPAR Trafficking and Gene Regulation in an In Vitro Model

Mitragynine inhibits hippocampus neuroplasticity and its molecular mechanism

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