Overstimulation of Glutamate Signals Leads to Hippocampal Transcriptional Plasticity in Hamsters

Vito, Anna Di; Mele, Maria Cristina; Piscioneri, Antonella; Morelli, Sabrina; Bartolo, Loredana De; Barni, Tullio; Facciolo, Rosa Maria; Canonaco, Marcello

doi:10.1007/s10571-014-0034-0

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…At this stage the physiological benefit of this adjustment of synapse plasticity is not clear. One possibility is that the downregulation of AMPA/NMDA receptor subunits and auxiliary subunits during torpor protects the brain against excitotoxicity 38 and limits energy consumption by reducing synaptic communication 20 , and that the temporary post-arousal boost in plasticity and memory are simply the result of an increased expression of these proteins required to prepare the brain for its normal function again. Alternatively, increased memory formation during arousal may in itself be important to maximize the animal's adaptive response to a new posttorpor environment, offering an evolutionary advantage of crucial importance in animals that use torpor as an emergency strategy.…”

Section: Discussionmentioning

confidence: 99%

Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

Mestdagh

Timmerman²,

Koopmans³

et al. 2021

Sci Rep

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Hibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

Mestdagh

Timmerman²,

Koopmans³

et al. 2021

Sci Rep

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“…After 3, 7, and 10 days of differentiation, untreated and ZOL-treated cells were rinsed with PBS, and total cellular ribonucleic acid (RNA) was extracted using TRIzol reagent (Life Technologies) according to the manufacturer’s instructions. The purity and the integrity check of each RNA sample, the reverse transcription of RNA, and Quantitative real-time PCR (q-RT-PCR) were performed as previously reported 30 . Briefly, complementary DNA (cDNA) was synthesized from 1 µg of RNA using a reverse transcriptase system kit (no.…”

Section: Methodsmentioning

confidence: 99%

Dose-Dependent Effects of Zoledronic Acid on Human Periodontal Ligament Stem Cells: An In Vitro Pilot Study

et al. 2020

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Bisphosphonates (BPs) are widely used to treat several metabolic and oncological diseases affecting the skeletal system. Despite BPs’ well-known therapeutic potential, they also displayed important side effects, among which is BPs-related osteonecrosis of the jaw, by targeting osteoclast activities, osteoblast, and osteocyte behavior. The aim of this study is to evaluate the biological effects of zoledronic acid (ZOL) in an in vitro model of periodontal ligament stem cells (PDLSCs) by using an experimental setting that resembles the in vivo conditions. PDLSCs were treated with different concentrations of ZOL ranging from 0.1 to 5 μM. The effects of ZOL exposure were evaluated on cell viability via 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazolium bromide (MTT), cell cycle analysis, apoptosis detection, and immunofluorescence. Quantitative real-time polymerase chain reaction (PCR), colorimetric detection of alkaline phosphatase activity, and Alizarin Red S staining were performed to investigate the osteogenic potential of PDLSCs exposed to ZOL. MTT analysis showed that the viability of PDLSCs exposed to ZOL concentration ≥1.5 μM for 3 and 6 days was significantly lower ( P < 0.001) than that of untreated cells. The percentage of apoptotic cells was significantly higher in PDLSCs exposed for 4 days to ZOL at 2 μM ( P < 0.01) and 5 μM ( P < 0.001) when compared to the control. Moreover, ZOL treatment (3 days) accounted for alterations in cell cycle distribution, with an increase in the proportion of cells in G0/G1 phase and a reduction in the proportion of cells in S phase. Chronic exposure (longer than 7 days) of PDLSCs to ZOL accounted for the downregulation of ALP, RUNX2, and COL1 genes at all tested concentrations, which fit well with the reduced alkaline phosphatase activity reported after 7 and 14 days of treatment. Reduced Col1 deposition in the extracellular matrix was reported after 14 days of treatment. Increased calcium deposits were observed in treated cells when compared to the control cultures. In conclusion, chronic exposure to 1 μM ZOL induced significant reduction of osteogenic differentiation, while ZOL concentrations ≥1.5 μM are required to impair PDLSCs viability and induce apoptosis.

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“…After 7, 14 and 21 days of differentiation, the cells were rinsed with PBS, and total cellular RNA was extracted using TRIzol reagent (Life Technologies) according to the manufacturer's instructions. The purity and the integrity check of each RNA sample, the reverse transcription of RNA and quantitative real-time polymerase chain reaction (q-RT-PCR) were performed as previously reported 18 . Briefly, cDNA was synthesized from 1 mg of RNA using a reverse transcriptase system kit (no.…”

Section: Quantitative Real-time Polymerase Chain Reactionmentioning

confidence: 99%

In Vitro Long-Term Expansion and High Osteogenic Potential of Periodontal Ligament Stem Cells: More Than a Mirage

et al. 2018

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The periodontal ligament displays a reservoir of mesenchymal stem cells which can account for periodontal regeneration. Despite the numerous studies directed at the definition of optimal culture conditions for long-term expansion of periodontal ligament stem cells (PDLSCs), no consensus has been reached as to what is the ideal protocol. The aim of the present study was to determine the optimal medium formulation for long-term expansion and stemness maintenance of PDLSCs, in order to obtain a sufficient number of cells for therapeutic approaches. For this purpose, the effects of three different culture medium formulations were evaluated on PDLSCs obtained from three periodontal ligament samples of the same patient: minimum essential medium Eagle, alpha modification (α-MEM), Dulbecco’s modified Eagle’s medium (DMEM), both supplemented with 10% fetal bovine serum (FBS), and a new medium formulation, Ham’s F12 medium, supplemented with 10% FBS, heparin 0.5 U/ml, epidermal growth factor (EGF) 50 ng/ml, fibroblast growth factor (FGF) 25 ng/ml, and bovine serum albumin (BSA) 1% (enriched Ham’s F12 medium; EHFM). PDLSCs grown in EHFM displayed a higher PE-CD73 mean fluorescence intensity compared with cells maintained in α-MEM and DMEM, even at later passages. Cells maintained in EHFM displayed an increased population doubling and a reduced population doubling time compared with cells grown in DMEM or α-MEM. α-MEM, DMEM and EHFM with added dexamethasone, 2-phospho-L-ascorbic acid, and β-glycerophosphate were all able to promote alkaline phosphatase activity; however, no calcium deposition was detected in PDLSCs cultured in EHFM-differentiation medium. When EHFM-, α-MEM- and DMEM-expanded PDLSCs were transferred to a commercial culture medium for the osteogenesis, mineralization became much more evident in confluent monolayers of EHFM-expanded PDLSCs compared with DMEM and α-MEM. The results suggest EHFM is the optimal medium formulation for growth and stemness maintenance of primary PDLSCs. Moreover, EHFM confers higher osteogenic potential to PDLSCs compared with cells maintained in the other culture media. Overall, the results of the present work confirmed the advantages of using EHFM for long-term expansion of mesenchymal cells in vitro and the preservation of high osteogenic potential.

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Overstimulation of Glutamate Signals Leads to Hippocampal Transcriptional Plasticity in Hamsters

Cited by 9 publications

References 46 publications

Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

Dose-Dependent Effects of Zoledronic Acid on Human Periodontal Ligament Stem Cells: An In Vitro Pilot Study

In Vitro Long-Term Expansion and High Osteogenic Potential of Periodontal Ligament Stem Cells: More Than a Mirage

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