Rapamycin, but not minocycline, significantly alters ultrasonic vocalization behavior in C57BL/6J pups in a flurothyl seizure model

Hodges, Samantha L.; Womble, Paige D.; Kwok, Eliesse M.; Darner, Alyssa M.; Senger, Savannah; Binder, Matthew S.; Faust, Amanda M.; Condon, Siena M.; Nolan, Suzanne O.; Quintero, None Saul I.; Lugo, Joaquín N.

doi:10.1016/j.bbr.2021.113317

Cited by 5 publications

(5 citation statements)

References 76 publications

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“…Mice used in this study were male and female adult neuron subset-specific Pten (NS- Pten ) conditional mice, previously described as GFAP-Cre; Pten loxP/loxP mice ( RRID: MGI:3714016 ; Hodges et al, 2018 , 2021 ). This mouse model has Cre activity mainly in hippocampal granule neurons of the dentate gyrus ( Backman et al, 2001 ; Kwon et al, 2001 ).…”

Section: Methodsmentioning

confidence: 99%

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Neuronal deletion of phosphatase and tensin homolog in mice results in spatial dysregulation of adult hippocampal neurogenesis

Latchney,

Ruiz Lopez,

Womble

et al. 2023

Front. Mol. Neurosci.

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Adult neurogenesis is a persistent phenomenon in mammals that occurs in select brain structures in both healthy and diseased brains. The tumor suppressor gene, phosphatase and tensin homolog deleted on chromosome 10 (Pten) has previously been found to restrict the proliferation of neural stem/progenitor cells (NSPCs) in vivo. In this study, we aimed to provide a comprehensive picture of how conditional deletion of Pten may regulate the genesis of adult NSPCs in the dentate gyrus of the hippocampus and the subventricular zone bordering the lateral ventricles. Using conventional markers and stereology, we quantified multiple stages of neurogenesis, including proliferating cells, immature neurons (neuroblasts), and apoptotic cells in several regions of the dentate gyrus, including the subgranular zone (SGZ), outer granule cell layer (oGCL), molecular layer, and hilus at 4 and 10 weeks of age. Our data demonstrate that conditional deletion of Pten in mice produces successive increases in dentate gyrus proliferating cells and immature neuroblasts, which confirms the known negative roles Pten has on cell proliferation and maturation. Specifically, we observe a significant increase in Ki67+ proliferating cells in the neurogenic SGZ at 4 weeks of age, but not 10 weeks of age. We also observe a delayed increase in neuroblasts at 10 weeks of age. However, our study expands on previous work by providing temporal, subregional, and neurogenesis-stage resolution. Specifically, we found that Pten deletion initially increases cell proliferation in the neurogenic SGZ, but this increase spreads to non-neurogenic dentate gyrus areas, including the hilus, oGCL, and molecular layer, as mice age. We also observed region-specific increases in apoptotic cells in the dentate gyrus hilar region that paralleled the regional increases in Ki67+ cells. Our work is accordant with the literature showing that Pten serves as a negative regulator of dentate gyrus neurogenesis but adds temporal and spatial components to the existing knowledge.

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Section: Methodsmentioning

confidence: 99%

“…Mice were provided with water and food ad libitum. All procedures were conducted in compliance with the Baylor University Institutional Animal Care and Use Committee and the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (Hodges et al, 2018(Hodges et al, , 2021.…”

Section: Micementioning

confidence: 99%

Neuronal deletion of phosphatase and tensin homolog in mice results in spatial dysregulation of adult hippocampal neurogenesis

Latchney,

Ruiz Lopez,

Womble

et al. 2023

Front. Mol. Neurosci.

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“…Flurothyl is a GABAA antagonist with epileptogenic ability [ 23 ]. Acute generalized tonic-clonic seizure mouse model can be established by flurothyl inhalation [ 24 - 26 ], which manifests as convulsions and tonic extension of the limbs [ 27 , 28 ]. The rats with recurrent seizures induced by flurothyl usually present reflex delay, poor adaptation to new environments, and poor memory and learning abilities [ 27 ].…”

Section: Generalized Tonic-clonic Seizure Modelsmentioning

confidence: 99%

Animal Models of Epilepsy: A Phenotype-oriented Review

Wang¹,

Wei²,

Feng³

et al. 2022

Aging and disease

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Epilepsy is a serious neurological disorder characterized by abnormal, recurrent, and synchronous discharges in the brain. Long-term recurrent seizure attacks can cause serious damage to brain function, which is usually observed in patients with temporal lobe epilepsy. Controlling seizure attacks is vital for the treatment and prognosis of epilepsy. Animal models, such as the kindling model, which was the most widely used model in the past, allow the understanding of the potential epileptogenic mechanisms and selection of antiepileptic drugs. In recent years, various animal models of epilepsy have been established to mimic different seizure types, without clear merits and demerits. Accordingly, this review provides a summary of the views mentioned above, aiming to provide a reference for animal model selection.

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“…Increasing investigations have demonstrated that phosphatidylinositol 3 (PI3K) signaling is an essential intracellular signaling system activated by brain inflammation (Le Belle et al 2014 ; Hodges et al 2021 ). PI3K is a family of lipid kinases that phosphorylate the 3′-hydroxyl group of phosphatidylinositide and phosphoinositides, controlling the activation of protein kinase B (PKB, also named AKT) and the mammalian target of rapamycin (mTOR) (Bilanges et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3β by Upregulating GRPR in Hippocampal Neurons of Autistic Mice

Li,

Wang,

et al. 2024

J Neuroimmune Pharmacol

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Autism spectrum disorder (ASD) is a neurological disorder associated with brain inflammation. The underlying mechanisms could be attributed to the activation of PI3K signaling in the inflamed brain of ASD. Multiple studies highlight the role of GRPR in regulating ASD like abnormal behavior and enhancing the PI3K signaling. However, the molecular mechanism by which GRPR regulates PI3K signaling in neurons of individuals with ASD is still unclear. In this study, we utilized a maternal immune activation model to investigate the effects of GRPR on PI3K signaling in the inflamed brain of ASD mice. We used HT22 cells with and without GRPR to examine the impact of GRP-GRPR on the PI3K-AKT pathway with IL-6 treatment. We analyzed a dataset of hippocampus samples from ASD mice to identify hub genes. Our results demonstrated increased expression of IL-6, GRPR, and PI3K-AKT signaling in the hippocampus of ASD mice. Additionally, we observed increased GRPR expression and PI3K-AKT/mTOR activation in HT22 cells after IL-6 treatment, but decreased expression in HT22 cells with GRPR knockdown. NetworkAnalyst identified GSK-3β as the most crucial gene in the PI3K-AKT/mTOR pathway in the hippocampus of ASD. Furthermore, we found that IL-6 upregulated the expression of GSK-3β in HT22 cells by upregulating GRP-GRPR. Our findings suggest that IL-6 can enhance the activation of PI3K-AKT/mTOR-GSK-3β in hippocampal neurons of ASD mice by upregulating GRPR. Graphical Abstract

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Rapamycin, but not minocycline, significantly alters ultrasonic vocalization behavior in C57BL/6J pups in a flurothyl seizure model

Cited by 5 publications

References 76 publications

Neuronal deletion of phosphatase and tensin homolog in mice results in spatial dysregulation of adult hippocampal neurogenesis

Neuronal deletion of phosphatase and tensin homolog in mice results in spatial dysregulation of adult hippocampal neurogenesis

Animal Models of Epilepsy: A Phenotype-oriented Review

IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3β by Upregulating GRPR in Hippocampal Neurons of Autistic Mice

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