Recurrent Hypoglycemia Increases Anxiety and Amygdala Norepinephrine Release During Subsequent Hypoglycemia

McNay, Ewan C.

doi:10.3389/fendo.2015.00175

Cited by 15 publications

(8 citation statements)

References 68 publications

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“…In this study, by subjecting adolescent rats to a typical Western-type obesogenic diet, we were able to reproduce various metabolic phenotypes associated with obesity. For instance, we observed postprandial hypoglycemia in the animals fed the WD, a condition commonly associated with anxiety and emotionality in both humans (Strachan et al, 2000) and rats (McNay, 2015). Not surprisingly, we report increased leptin levels in the rats that consumed the WD, and a robust correlation between TG and leptin.…”

Section: Discussionmentioning

confidence: 96%

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

Kalyan-Masih

Vega-Torres

Miles

et al. 2016

eNeuro

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Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 96%

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

Kalyan-Masih

Vega-Torres

Miles

et al. 2016

eNeuro

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“…Previous animal studies examining spatial working memory and hippocampal function reported that RH enhances spatial working memory in rats in euglycemia but impairs it during subsequent hypoglycemic episodes . Reports also demonstrate increased anxiety in previously RH‐exposed rats during acute hypoglycemia and decreased mental flexibility when euglycemic . Furthermore, the hippocampal synaptic function was found to be markedly impaired in RH‐exposed rats during further hypoglycemic conditions .…”

Section: Introductionmentioning

confidence: 91%

Exposure to recurrent hypoglycemia alters hippocampal metabolism in treated streptozotocin‐induced diabetic rats

et al. 2019

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AimsExposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose‐lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin‐diabetic rats.MethodsHyperglycemia was corrected by insulin pellet implantation. Insulin‐treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days.ResultsThe effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH‐exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure.ConclusionOur results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin‐treated streptozotocin‐diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions.

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“…Exposure of ITD rats to RH-RH was induced 2-3 weeks after insulin pellet implantation, with the aim of maintaining blood glucose levels in the moderate hypoglycemia range for 3 hours, by s.c. injection of Novolog (insulin aspart, Novo Nordisk, AIS, Denmark) (Dave, et al, 2011). Duration, frequency and total number of hypoglycemia episodes was decided based on earlier studies (McNay et al, 2006;Herzog et al, 2008;Won, et al, 2012;McNay, 2015). Glucose levels were measured at baseline and every hour during hypoglycemia.…”

Section: Induction Of Diabetes-malementioning

confidence: 99%

Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Diabetic Rats via Enhanced Post-Ischemic Mitochondrial Dysfunction

Shukla

Fuchs

Liu

et al. 2018

Transl. Stroke Res.

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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.

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Recurrent Hypoglycemia Increases Anxiety and Amygdala Norepinephrine Release During Subsequent Hypoglycemia

Cited by 15 publications

References 68 publications

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

Exposure to recurrent hypoglycemia alters hippocampal metabolism in treated streptozotocin‐induced diabetic rats

Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Diabetic Rats via Enhanced Post-Ischemic Mitochondrial Dysfunction

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