scholarly journals Tau Phosphorylation and Sevoflurane Anesthesia

2012 ◽  
Vol 116 (4) ◽  
pp. 779-787 ◽  
Author(s):  
Hélène Le Freche ◽  
Jonathan Brouillette ◽  
Francisco-José Fernandez-Gomez ◽  
Pauline Patin ◽  
Raphaëlle Caillierez ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Animal Studies ◽  
Postoperative Cognitive Dysfunction ◽  
Tau Phosphorylation ◽  
Anesthetic Agent ◽  
Sevoflurane Anesthesia ◽  
Anesthetic Agents ◽  
Pathologic Features

Background There is a growing interest in the involvement of anesthetic agents in the etiology of postoperative cognitive dysfunction. Recent animal studies suggest that acute anesthesia induces transient hyperphosphorylation of tau, an effect essentially ascribed to hypothermia. The main aim of the present study was to investigate effects, in normothermic conditions, of acute or repeated exposure to sevoflurane, a halogenated anesthetic agent, on hippocampal tau phosphorylation and spatial memory in adult mice. Methods 5 to 6-month-old C57Bl6/J mice were submitted to acute (1 h) or repeated (five exposures of 1h every month) anesthesia using 1.5 or 2.5% sevoflurane, in normothermic conditions. In the acute protocol, animals were sacrificed 1 and 24 h after exposure. In the chronic protocol, spatial memory was evaluated using the Morris water maze following the fourth exposure, and tau phosphorylation evaluated 1 month following the last exposure using bi- and mono-dimensional electrophoresis. Results Acute sevoflurane anesthesia in normothermic conditions led to a significant dose-dependent and reversible hippocampal tau phosphorylation, 1 h following the end of exposure (P < 0.001). Conversely, repeated anesthesia led to persistent tau hyperphosphorylation and significant memory impairments, as seen in the retention phase of the Morris water maze in sevoflurane-anesthesized animals. These pathologic features may be related to the activation of both Akt and Erk pathways. Conclusions The present study demonstrates, in mice, that sevoflurane exposure is associated with increased tau phosphorylation through specific kinases activation and spatial memory deficits. These data support a correlation between exposures to this anesthetic agent and cognitive decline.

scholarly journals Sevoflurane Anesthesia Does Not Impair Acquisition Learning or Memory in the Morris Water Maze in Young Adult and Aged Rats

2012 ◽  
Vol 117 (5) ◽  
pp. 1091-1101 ◽  
Author(s):  
Jennifer K. Callaway ◽  
Nigel C. Jones ◽  
Alistair G. Royse ◽  
Colin F. Royse
Keyword(s):  
Young Adult ◽  
Morris Water Maze ◽  
Water Maze ◽  
Postoperative Cognitive Dysfunction ◽  
Reference Memory ◽  
Potential Contribution ◽  
Aged Rats ◽  
Sevoflurane Anesthesia ◽  
Morris Water Maze Task ◽  
Sham Exposure

Background Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. Methods The effects of anesthesia with 1 minimum alveolar concentration of sevoflurane for 4 h or sham exposure on cognition were investigated in young adult and aged (20-24 months) rats at 1, 4, and 12 weeks postexposure. Spatial reference memory acquisition and retention were tested in the Morris water maze task. Latency to locate the hidden platform and swim speed were determined and compared between treatments. Results Sevoflurane anesthesia significantly reduced latency to find the hidden platform in both young adult (n = 10 per treatment, P < 0.0001) and aged rats (n = 7 per treatment, P < 0.0001) when tested 1 week after exposure. In young rats only, this improved acquisition learning was maintained at 4 (P = 0.003) but not at 12 weeks postexposure (P = 0.061). There were no differences in swim speed or in open field exploration between groups (no confounding effects of stress or locomotion). Retention memory measured using probe trials was not affected by exposure to sevoflurane in young adult or aged rats. Conclusion Sevoflurane anesthesia did not impair acquisition learning and retention memory in young adult or aged rats.

scholarly journals Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Rat Model ◽  
Gut Microbiome ◽  
Water Maze ◽  
Single Injection ◽  
Postoperative Cognitive Dysfunction ◽  
Aged Rats ◽  
Short Term ◽  
Term Memory

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud Hashemzaei ◽  
Najmeh Baratzadeh ◽  
Iraj Sharamian ◽  
Sahar Fanoudi ◽  
Mehdi Sanati ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Spatial Memory ◽  
Morris Water Maze ◽  
Spatial Learning ◽  
Water Maze ◽  
Synergistic Effects ◽  
Deionized Water ◽  
Learning Deficits ◽  
Learning Impairments ◽  
Morris Water Maze Task

Abstract Objectives H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. Methods Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 μg/μL, dissolved in saline) or O-acetyl-L-carnitine (100 μM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. Results The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. Conclusions Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

scholarly journals Rapamycin attenuated zinc-induced tau phosphorylation and oxidative stress in animal model: Involvement of dual mTOR/p70S6K and Nrf2/HO-1 pathways

2021 ◽  
Author(s):  
Chencen Lai ◽  
Qian Chen ◽  
Yuanting Ding ◽  
Songbai Su ◽  
Heng Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Zinc Sulfate ◽  
Water Maze ◽  
Tau Phosphorylation ◽  
Alzheimers Disease ◽  
Tau Pathology ◽  
Biochemical Assays ◽  
And Oxidative Stress

Alzheimers disease is pathologically featured by abnormal accumulation of amyloid-beta plaque, neurofibrillary tangles, oxidative stress, neuroinflammation, and neurodegeneration. Metal dysregulation including excessive zinc released by presynaptic neurons plays an important role in tau pathology and oxidase activation. The activities of mammalian target of rapamycin (mTOR)/ ribosomal S6 protein kinase (p70S6K) are elevated in the brains of patients with Alzheimers disease. Zinc induces tau hyperphosphorylation via mTOR/P70S6K activation in vitro. However, the involvement of mTOR/P70S6K pathway in zinc-induced oxidative stress, tau degeneration, synaptic and cognitive impairment, has not been fully elucidated in vivo. Here we assessed in the effect of pathological concentration of zinc in SH-SY5Y cells by using biochemical assays and immunofluorescence staining. Rats (n = 18, male) were lateral ventricularly-injected with zinc and treated with rapamycin (intraperitoneal injection) for one week and assessed using Morris water maze. Evaluation of the oxidative stress, tau phorsphylation and synaptic impairment were performed using the hippocampus tissue of the rats by biochemical assays and immunofluorescence staining. Results from Morris water maze showed that the capacity of spatial memory is impaired in zinc-treated rats. Zinc sulfate significantly increased the levels of P-mTOR Ser2448, P-p70S6K Thr389, and P-tau Ser356, and decreased levels of Nrf2 and HO-1 in SH-SY5Y cells and in zinc-treated rats compared with control groups. Increased expressions of reactive oxygen species were observed in zinc sulfate-induced SH-SY5Y cells as well as in the hippocampus of zinc-injected rats. Rapamycin, an inhibitor of mTOR, rescued the zinc-induced increases in mTOR/p70S6K activations, tau phosphorylation and oxidative stress, as well as Nrf2/HO-1 inactivation, cognitive impairment and synaptic impairment reduced the expression of synapse-related proteins in zinc-injected rats. In conclusion, our findings imply that rapamycin prevents zinc-induced cognitive impairment and protects neurons from tau pathology, oxidative stress and synaptic impairment, by decreasing mTOR/p70S6K hyperactivity and increasing Nrf2/HO-1 activity.

scholarly journals Long-term potentiation is independent of the C-tail of the GluA1 AMPA receptor subunit

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Javier Díaz-Alonso ◽  
Wade Morishita ◽  
Salvatore Incontro ◽  
Jeffrey Simms ◽  
Julia Holtzman ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Morris Water Maze ◽  
Ampa Receptor ◽  
Water Maze ◽  
Long Term Potentiation ◽  
Receptor Subunit ◽  
Terminal Domain ◽  
Term Potentiation ◽  
Ampa Receptor Subunit

We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture passively diffusing AMPARs.

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