Mitochondrial Events Determine the Status of Hippocampal Cells in the Post-Ischemic Period.
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SUBMITTER: Lushnikova I
PROVIDER: S-EPMC8353033 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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Mitochondrial Events Determine the Status of Hippocampal Cells in the Post-Ischemic Period.
Lushnikova Iryna I Nikandrova Yelyzaveta Y Skibo Galyna G
Neuroscience bulletin 20210607 8
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Project description:BackgroundHippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.MethodsPilocarpine was used to induced SE in mice. SE-generated cognitive decline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics.ResultsThe results showed that peripheral administration of isolated mitochondria could improve cognitive deficits and depressive and anxiety-like behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, proliferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D-fructose-1,6-bisphosphate.ConclusionTo the best of our knowledge, these findings provide the first direct experimental evidence that artificial mitochondrial transplantation is capable of ameliorating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiatric and cognitive disorders.
| S-EPMC9986225 | biostudies-literature
Project description:Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here we used fMRI to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- and low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high-reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high-reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation.
| S-EPMC4777629 | biostudies-literature
Project description:Background: Monitoring nutritional status data in the adult population is extremely important to mediate their health status. Unfortunately, for Slovenia (2.1 million European Union citizens), data on the body composition status of the general adult population are currently rare or nonexistent in scientific journals. Furthermore, dietary intake was last assessed several years before the COVID-19 epidemic period. Methods: We randomly recruited 844 adult Slovenes from all regions of Slovenia. The primary aim of the cross-sectional study was to examine body composition status (using a medically approved electrical bioimpedance monitor) during the post-COVID-19 epidemic period. In addition, we assessed dietary intake (using a standardized food frequency questionnaire) and compared the obesity propensity for both sexes separately using the body mass index (BMI) and body fat percentage (FAT%) obesity classification of the World Health Organization. Results: Regarding BMI classification, 43% of the whole sample was overweight (28%) or obese (15%), and there were more older adults than adults (64% vs. 42%, p < 0.001). The average FAT% of adult females and males was 26.9% and 19.5% (p < 0.001), respectively, while for older adult females and males, it was 32.7% and 23% (p < 0.001). In addition, a comparison of the proportions of obese people between the two cut-off obesity classifications (BMI vs. FAT%) showed a significantly underestimated proportion of obese female participants based on BMI classification (13% vs. 17%, p = 0.005). In terms of the dietary intake of the assessed nutrients in comparison with the national dietary reference values for energy and nutrient intake, the participants, on average, had lower intake than the recommended values for carbohydrates, fiber, vitamins C, D and E (for males) and calcium, and higher intake than the recommended values for total fat, saturated fatty acids, cholesterol, sodium and chloride (for males). Conclusions: The results urgently call for the need to not only improve the overall national nutritional status but also for regular national monitoring of body composition and dietary intake statuses.
| S-EPMC9777729 | biostudies-literature
Project description:The coordination of dynamic neural activity within and between neural networks is believed to underlie normal cognitive processes. Conversely, cognitive deficits that occur following neurological insults may result from network discoordination. We hypothesized that cognitive outcome following febrile status epilepticus (FSE) depends on network efficacy within and between fields CA1 and CA3 to dynamically organize cell activity by theta phase. Control and FSE rats were trained to forage or perform an active avoidance spatial task. FSE rats were sorted by those that were able to reach task criterion (FSE-L) and those that could not (FSE-NL). FSE-NL CA1 place cells did not exhibit phase preference in either context and exhibited poor cross-theta interaction between CA1 and CA3. FSE-L and control CA1 place cells exhibited phase preference at peak theta that shifted during active avoidance to the same static phase preference observed in CA3. Temporal coordination of neuronal activity by theta phase may therefore explain variability in cognitive outcome following neurological insults in early development.
| S-EPMC4909381 | biostudies-literature
Project description:Replay of hippocampal place cell sequences has been proposed as a fundamental mechanism of learning and memory. However, the standard interpretation of replay has been challenged by reports that similar activity is observed before experience ('preplay'). By the preplay account, pre-existing temporal sequences are mapped onto new experiences without learning sequential structure. Here we employed high density recording methods to monitor hundreds of place cells simultaneously while rats explored multiple novel environments. While we observed large numbers of synchronous spiking events before experience, they were not temporally correlated with subsequent experience. Multiple measures differentiated pre-experience and postexperience events that, taken together, defined the latter but not the former as trajectory-depicting. The formation of events with these properties was prevented by administration of an NMDA-receptor antagonist during experience. These results suggest that the sequential structure of behavioral episodes is encoded during experience and reexpressed as trajectory events.
| S-EPMC6095134 | biostudies-literature
Project description:Diabetes significantly increases the risk of stroke and post-stroke mortality. Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose-lowering therapies. Earlier, we showed that RH in a rat model of insulin-dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial function has been implicated as a central player in the development of cerebral ischemic damage. Hypoglycemia is also known to affect mitochondrial functioning. The present study tested the hypothesis that prior exposure of insulin-treated diabetic (ITD) rats to RH exacerbates brain damage via enhanced post-ischemic mitochondrial dysfunction. In a rat model of streptozotocin-induced diabetes, we evaluated post-ischemic mitochondrial function in RH-exposed ITD rats. Rats were exposed to five episodes of moderate hypoglycemia prior to the induction of cerebral ischemia. We also evaluated the impact of RH, both alone and in combination with cerebral ischemia, on cognitive function using the Barnes circular platform maze test. We observed that RH exposure to ITD rats leads to increased cerebral ischemic damage and decreased mitochondrial complex I activity. Exposure of ITD rats to RH impaired spatial learning and memory. Our results demonstrate that RH exposure to ITD rats potentially increases post-ischemic damage via enhanced post-ischemic mitochondrial dysfunction.
| S-EPMC6151180 | biostudies-literature
Project description:The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from TNFα Tg rats showed significantly greater levels of long-term potentiation (LTP) in response to 100 Hz stimulation, suggesting that synaptic networks may be hyperexcitable in the context of elevated TNFα. Cognitive and motor deficits (assessed on the Morris Water Maze and Rotarod task, respectively) were present in TNFα Tg rats in the absence of significant differences in the loss of cortical and hippocampal neurons. TNF overexpression exacerbated MCAO-dependent deficits on the rotarod, but ameliorated cortical neuron loss in response to MCAO.
| S-EPMC4856338 | biostudies-literature
Project description:The hippocampus is critical to remembering the flow of events in distinct experiences and, in doing so, bridges temporal gaps between discontiguous events. Here, we report a robust hippocampal representation of sequence memories, highlighted by "time cells" that encode successive moments during an empty temporal gap between the key events, while also encoding location and ongoing behavior. Furthermore, just as most place cells "remap" when a salient spatial cue is altered, most time cells form qualitatively different representations ("retime") when the main temporal parameter is altered. Hippocampal neurons also differentially encode the key events and disambiguate different event sequences to compose unique, temporally organized representations of specific experiences. These findings suggest that hippocampal neural ensembles segment temporally organized memories much the same as they represent locations of important events in spatially defined environments.
| S-EPMC3163062 | biostudies-literature
Project description:Renal scintigraphy of a renal graft is a non-invasive imaging used to evaluate renal graft dysfunction in relay postoperative period. We presented the case of a 42-year-old man when underwent renal transplantation and developed anuria with severe renal impairment. Renal scintigraphy yielded no visualization of the renal graft. Subsequently, the patient underwent an exploratory laparotomy. The graft was found to have normal perfusion, and a surgical biopsy suggestive of an acute perfusion injury and mild tubular necrosis. The patient recovered with conservative therapy. This case highlights a common limitation of renal scintigraphy in a post-renal-transplantation patient with severe renal impairment.
| S-EPMC7066220 | biostudies-literature
Project description:BackgroundChildhood maltreatment (CM) exerts various long-lasting psychological and biological changes in affected individuals, with inflammation being an interconnecting element. Besides chronic low-grade inflammation, CM might also affect the energy production of cells by altering the function and density of mitochondria, i.e. the body's main energy suppliers. Here, we compared mitochondrial respiration and density in intact peripheral blood mononuclear cells (PBMC), from women with and without CM between two time points, i.e. at the highly inflammatory phase within 1 week after parturition (t0) and again after 1 year (t2).MethodsCM exposure was assessed with the Childhood Trauma Questionnaire. Whole blood was collected from n = 52 healthy women within the study 'My Childhood - Your Childhood' at both time points to isolate and cryopreserve PBMC. Thawed PBMC were used to measure mitochondrial respiration and density by high-resolution respirometry followed by spectrophotometric analyses of citrate-synthase activity.ResultsOver time, quantitative respiratory parameters increased, while qualitative flux control ratios decreased, independently of CM. Women with CM showed higher mitochondrial respiration and density at t0, but not at t2. We found significant CM group × time interaction effects for ATP-turnover-related respiration and mitochondrial density.ConclusionsThis is the first study to longitudinally investigate mitochondrial bioenergetics in postpartum women with and without CM. Our results indicate that CM-related mitochondrial alterations reflect allostatic load, probably due to higher inflammatory states during parturition, which normalize later. However, later inflammatory states might moderate the vulnerability for a second-hit on the level of mitochondrial bioenergetics, at least in immune cells.
| S-EPMC10317795 | biostudies-literature