Biology subjects

Steinberg, L.

Publications and source records attributed to Steinberg, L..

3 recordsLinked to original sources

bioRxiv2024

The selfish yet forgetful brain: Stable cerebral oxygen metabolism during hypoglycemia but impaired memory consolidation

The continuous supply of glucose and oxygen is essential for healthy brain function. Accordingly, the Selfish Brain Theory proposes that the human brain prioritizes its own energy demands, making it less vulnerable to fluctuations in systemic energy availability. Although studies have reported decreases in cerebral glucose metabolism, alternative energy sources other than glucose might be oxidized for ATP production. However, cerebral oxygen metabolism (CMRO2) has never been quantified across the human brain. In this study, we investigated the influence of insulin-induced hypoglycemia on CMRO2 in healthy male participants. Additionally, we explored the prolonged effects of hypoglycemia on cognitive function following the restoration of euglycemia. We found that CMRO2 remained stable under hypoglycemia, even at blood glucose levels below 49 mg/dL. Interestingly, we detected a significant increase in cerebral blood flow (CBF) of up to 11%, particularly in regions involved in higher cognitive processing. Despite stable rates of oxygen metabolism, we identified a selective impairment in memory consolidation following hypoglycemia, even after normal glucose levels were restored, with no effects observed in memory encoding or attention. In favor of the Selfish Brain Theory, the stability in CMRO2 suggests that the brain efficiently shifts to alternate energy pathways under hypoglycemia, potentially using astrocytic glycogen. Despite this metabolic flexibility, our results indicate that prior hypoglycemia imposes long-lasting effects on memory consolidation, possibly linked to glycogen depletion and impaired glutamate synthesis. In summary, our study suggests that clinical states of hypoglycemia pose a critical impact on patient brain health and functioning.

neuroscience↗

bioRxiv2020

Sleep and Diurnal Rest-Activity Rhythm Disturbances in a Mouse Model of Alzheimer's Disease

Study ObjectivesAccumulating evidence suggests a strong association between sleep, amyloid-beta (A{beta}) deposition, and Alzheimers disease (AD). We sought to determine if: (1) deficits in rest-activity rhythms and sleep are significant phenotypes in J20 AD mice, (2) metabotropic glutamate receptor 5 inhibitors (mGluR5) could rescue deficits in rest-activity rhythms and sleep, and (3) A{beta} levels are responsive to treatment with mGluR5 inhibitors. MethodsDiurnal rest-activity levels were measured by actigraphy and sleep-wake patterns by electroencephalography (EEG), while animals were chronically treated with mGluR5 inhibitors. Behavioral tests were performed, and A{beta} levels measured in brain lysates. ResultsJ20 mice exhibited a 4.5 hour delay in the acrophase of activity levels compared to wild-type littermates, and spent less time in REM sleep during the second half of the light period. J20 mice also exhibited decreased NREM delta power but increased NREM sigma power. The mGluR5 inhibitor CTEP rescued the REM sleep deficit and improved NREM delta and sigma power but did not correct rest-activity rhythms. No statistically significant differences were observed in A{beta} levels, rotarod performance or the passive avoidance task following chronic mGluR5 inhibitor treatment. ConclusionsJ20 mice have disruptions in rest-activity rhythms and reduced homeostatic sleep pressure (reduced NREM delta power). NREM delta power was increased following treatment with an mGluR5 inhibitor. Drug bioavailability was poor. Further work is necessary to determine if mGluR5 is a viable target for treating sleep phenotypes in AD. Statement of SignificanceSleep disruption is evolving as an important risk factor as well as phenotype of neurological diseases including Alzheimers disease. This study is novel in determining alterations in the rest-activity rhythm and sleep-wake pattern of J20 Alzheimers disease mice and wild type littermates. Specifically, there is a delay in acrophase with prolonged hyperactivity during the dark cycle, and reduced sleep pressure that was improved by treatment with mGluR5 inhibitor. Critical remaining knowledge gaps and future directions include testing the effects of Alzheimers disease drugs on rescue of sleep and rest-activity patterns in other Alzheimers disease models. These studies are relevant to human Alzheimers disease as monitoring sleep phenotypes may predict disease risk, and therapies that normalize sleep patterns may slow progression.

neuroscience↗

bioRxiv2017

Connecting Brain Responsivity And Real-World Risk Taking: Strengths And Limitations Of Current Methodological Approaches

In line with the goal of limiting health risk behaviors in adolescence, a growing literature investigates whether individual differences in functional brain responses can be related to vulnerability to engage in risky decision-making. We review this body of work, investigate when and in what way findings converge, and provide best practice recommendations. We identified 23 studies that examined individual differences in brain responsivity and adolescent risk taking. Findings varied widely in terms of the neural regions identified as relating to risky behavior. This heterogeneity is likely due to the abundance of approaches used to assess risk taking, and to the disparity of fMRI tasks. Indeed, brain-behavior correlations were typically found in regions showing a main effect of task. However, results from a test of publication bias suggested that region of interest approaches lacked evidential value. The findings suggest that neural factors differentiating riskier teens are not localized to a single region. Therefore, approaches that utilize data from the entire brain, particularly in predictive analyses, may yield more reliable and applicable results. We discuss several decision points that researchers should consider when designing a study, and emphasize the importance of precise research questions that move beyond a general desire to address adolescent risk taking.

neuroscience↗