435 research outputs found

    EXCITOTOXIC LESIONS OF THE PARABRACHIAL NUCLEI PREVENT CONDITIONED TASTE-AVERSIONS AND SODIUM APPETITE IN RATS

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    Electrolytic lesions of the parabrachial nuclei (PEN) disrupt conditioned taste aversion (CTA) in the rat, but it is not known whether this effect is due to damaging axons of passage or to destruction of intrinsic neurons. We tested 10 rats with electrophysiologically guided, ibotenic acid lesions of the PEN (PBNx) to determine whether they could acquire a LiCl-induced CTA to l-alanine (0.3 M) or demonstrate a sodium appetite following furosemide treatment and overnight access to sodium deficient chow. Vehicle-treated and nonsurgical controls were included in the design. PBNx rats failed to develop a CTA, even after 3 conditioning trials. Moreover, more than 8 months later, a subset of the PBNx rats were again unable to learn a CTA using NaCl as the conditional stimulus (CS). After the furosemide treatment, the control rats drank an average of 20.3 mi of strong salt in 24 hr. The PBNx rats drank virtually no NaCl during the first 2 hr and averaged only 4.0 mi in 24 hr. In the PEN, damage to neuronal somata is more critical than interrupting fibers of passage for producing deficits in taste-guided behaviors

    Gustatory functions, sodium appetite, and conditioned taste aversion survive excitotoxic lesions of the thalamic taste area

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    Rats with bilateral, electrophysiologically guided, ibotenic acid lesions of the gustatory thalamus (THLX) were tested for their ability to perform a variety of taste-guided behaviors. First, in daily 30-min sessions, the rats were given repeated 10-s access periods to a range of concentrations of sucrose, NaCl, or QHCl, plus water. Both the control and the THLX rats exhibited similar concentration-response functions, regardless of hydrational state. Next, on 3 trials, the rats were given 15 min access to 0.3 M l-alanine and then injected with LiCl (0.15 M, 1.33 ml/100 g body weight ip). All rats learned a taste aversion following 1 pairing with LiCl. Finally, on 3 separate occasions, the rats were injected with furosemide, and Na+-appetite was evaluated 24 hr later. All rats expressed an equivalent sodium appetite after the first furosemide injection, but only the control rats increased intake of 0.51 M NaCl with repeated sodium depletions. These observations reinforce prior data implying that an intact gustatory thalamus is not necessary for the expression of some taste-guided behaviors

    Talking to Chloe : learning to appreciate the meta-perspective of children’s thoughts

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    Mimmi Norgren Hansson explores the essential aspects of respect and empathy within the context of research involving children. While empathy in interviews commonly revolves around recognizing and understanding participants’emotions and experiences, this chapter seeks to broaden the scope by highlighting the significance of respecting and appreciating children’s analytical abilities and statements. Drawing inspiration from a memorable encounter with twelve years old Chloe, the author incorporates her analysis of care as a preface to the argument. </p

    Gustatory detection thresholds after parabrachial nuclei lesions in rats

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    Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment 2) that had been electrophysiologically centered in the gustatory zone of the parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection thresholds in a conditioned avoidance task. With 1 exception, all of these rats had previously shown severe deficits in acquiring an LiCl-based conditioned taste aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions also had failed to express a depletion-induced sodium appetite. Despite the uniformity of these deficits, the rats with lesions exhibited varied performance in the detectability task. Roughly 1/3 of the rats did not perform competently, 1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in taste detectability. These findings demonstrate that the elimination of CTA following PBN lesions is not necessarily linked to an impairment in taste signal detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely correspond with impairments on another

    The impact of macronutritional composition and ketosis on cognitive health : from normal aging to Alzheimer’s disease

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    Ketogenic diets (KD) are increasingly investigated for the prevention of cognitive decline and Alzheimer’s disease (AD). Without explicitly investigating a KD, this thesis disentangles two of its hallmarks: a reduced dietary carbohydrate/fat-ratio (CFr) and the metabolic state ketosis. Whether health effects from KD are primarily driven by ketosis or from other pathways related macronutritional changes, is not fully understood. Beyond CFr, KD may optionally be modified regarding protein, fat-subtypes, plant/animal-based food proportions, the timing of nutrient intake, and ketogenic supplements.Strategies to induce ketosis in the absence of a carbohydrate restricted diet (Study I) and subsequent associations between induced ketosis and a biomarker essential for brain function (Study II) was investigated in a randomized clinical trial planned and performed within this doctoral project: In a 6-arm cross-over design, 15 healthy older adults (age 65-73, following their usual diet) were exposed to intake of oils with various composition of medium-chain triglycerides (MCT), with and without glucose. Blood levels of ketones (β-hydroxybutyrate, BHB) and brain-derived neurotrophic factor (BDNF) were thereafter monitored for 4 hours. Mature BDNF (mBDNF) and its precursor proBDNF are essential for brain plasticity, and their concentrations in serum have been associated with cognitive health. A methods comparison for measuring blood ketones (Study III) supports the internal validity of Study I and II.The impact of self-reported CFr—in the non-ketogenic range—on cognitive performance (Study IV/V) was investigated by panel analyses on data (year 0, 1, and 2) from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). The sample (n=1259, age 60–77, 47% females) had no substantial cognitive impairment but had risk factors for developing dementia, and cognition at mean level or slightly lower than expected in screening test. Study V added stratified analyses based on genetics (APOE) and insulin status.Study I: A 16-hour non-carbohydrate window and intake of 20 g caprylic acid (C8) contributed roughly equally to induce transient ketosis (0.45 mmol/L, AUC/time venous BHB hour 0-4, when combining the strategies). Coconut oil (which has a ≈7% fraction constituted by C8 and is dominated by lauric acid) did not share the ketogenic properties of purified C8 (difference –0.22 mmol/L, pStudy II: Contrary to our expectations, change in mBDNF was lower (z-score: β=–0.88, pStudy III: A handheld ketone meter correlated well with the laboratory method (r=0.91) and agreement was high when applied to venous whole blood (which was our primary outcome). However, absolute values were systematically higher in capillary blood, which should be considered in comparisons between studies.Study IV: A lower CFr (log, z-score) estimated a higher composite z-score on a Neuropsychological Test Battery ( β=–0.022, p=0.011) in linear mixed regression. Methodological advantages of analyzing intake of carbohydrates and fat as a ratio compared to single variables were discussed. No significant associations were found for protein, and the saturated/total fat ratio had non-linear associations with cognitive performance.Study V: APOE (-2/3/4), which is the most important AD risk gene, modified estimates between diet parameters (CFr, protein, saturated/total fat ratio, fiber, composite score) and cognitive performance in a sub-sample with insulin data, excluding diabetics (n=676). By increasing values of a continuous APOE-gradient [–1 (-23), –0.5 (-24), 0 (-33), 1 (-34), 2 (-44)], a less favorable estimate (pcognition in a dose dependent manner, primarily among -34/44. The plant/animal-based proportion of macronutrients was discussed as a potential unmeasured confounder.Conclusions: Macronutritional changes may be an alternative explanation to ketosis for what may drive potential cognitive effects from KD. Time-restricted carbohydrate intake may be considered as an alternative, or a complement, to C8-enriched MCT-oils for achieving mild ketosis. Signaling functions of ketones may be at work in transient mild/moderate ketosis, but whether our BDNF results have any cognitive implications requires further studies. To guide further research, our diet ->cognition analyses have strengthened the case for: (1) a precision nutrition approach based on APOE-genotype and insulin status; (2) not limiting interventions on carbohydrate restriction to the ketogenic range of CFr; (3) considering both ends of the insulin spectrum as representing distinct at-risk types susceptible to diet modifications. APOE-34/44 carriers may be optimal targets for studying potential benefits on brain health from CFr-reduction, and higher protein intake. The concept of universal macronutrient targets may be questioned, and stratified analyses may be encouraged in further studies.List of scientific papersI. Ketosis After Intake of Coconut Oil and Caprylic Acid—With and Without Glucose: A Cross-Over Study in Healthy Older Adults. Norgren J, Sindi S, Sandebring-Matton A, Kåreholt I, Daniilidou M, Akenine U, Nordin K, Rosenborg S, Ngandu T, Kivipelto M. Frontiers in Nutrition. 2020;7:40. https://doi.org/10.3389/fnut.2020.00040 II. Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults. Norgren J, Daniilidou M*, Kåreholt I, Sindi S, Akenine U, Nordin K, Rosenborg S, Ngandu T, Kivipelto M, Sandebring-Matton A. Frontiers in Aging Neuroscience. 2021;13. *Shared 1st author. https://doi.org/10.3389/fnagi.2021.716594 III. Capillary Blood Tests May Overestimate Ketosis: Triangulation Between Three Different Measures of b-Hydroxybutyrate. Norgren J, Sindi S, Sandebring-Matton A, Kåreholt I, Akenine U, Nordin K, Rosenborg S, Ngandu T, Kivipelto M. American Journal of Physiology Endocrinology and Metabolism. 2020;318(2):E184-E8. https://doi.org/10.1152/ajpendo.00454.2019 IV. The Dietary Carbohydrate/Fat-ratio and Cognitive Performance: Panel Analyses in Older Adults at Risk for Dementia. Norgren J, Sindi S, Sandebring-Matton A, Ngandu T, Kivipelto M, Kåreholt I. Current Developments in Nutrition. May 3, 2023. [Accepted] https://doi.org/10.1016/j.cdnut.2023.100096 V. APOE-genotype and Insulin Modulate Estimates Between Dietary Macronutrients and Cognitive Performance: Panel Analyses in Non-Diabetic Older Adults at Risk for Dementia. Norgren J, Sindi S, Sandebring-Matton A, Kivipelto M, Kåreholt I. [Manuscript] https://doi.org/10.1016/j.tjnut.2023.09.016 </p

    sj-pdf-1-vmj-10.1177_1358863X211038620 – Supplemental material for World regional differences in outcomes for patients with peripheral artery disease: Insights from the EUCLID trial

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    Supplemental material, sj-pdf-1-vmj-10.1177_1358863X211038620 for World regional differences in outcomes for patients with peripheral artery disease: Insights from the EUCLID trial by Lars Norgren, Rebecca North, Iris Baumgartner, Jeffrey S Berger, Juuso I Blomster, William R Hiatt, W Schuyler Jones, Brian G Katona, Kenneth W Mahaffey, Hillary Mulder, Manesh R Patel, Frank W Rockhold and F Gerry R Fowkes in Vascular Medicine</p

    VMJ775594_Supplementary_material – Supplemental material for Ticagrelor versus clopidogrel in patients with symptomatic peripheral artery disease and prior coronary artery disease: Insights from the EUCLID trial

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    Supplemental material, VMJ775594_Supplementary_material for Ticagrelor versus clopidogrel in patients with symptomatic peripheral artery disease and prior coronary artery disease: Insights from the EUCLID trial by Jeffrey S Berger, Beth L Abramson, Renato D Lopes, Gretchen Heizer, Frank W Rockhold, Iris Baumgartner, F Gerry R Fowkes, Peter Held, Brian G Katona, Lars Norgren, W Schuyler Jones, Marcus Millegård, Juuso Blomster, Craig Reist, William R Hiatt, Manesh R Patel and Kenneth W Mahaffey in Vascular Medicine</p

    10.1177_1358863X19864172_Supplementary_tables – Supplemental material for Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial

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    Supplemental material, 10.1177_1358863X19864172_Supplementary_tables for Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial by Charles W Hopley, Sarah Kavanagh, Manesh R Patel, Cara Ostrom, Iris Baumgartner, Jeffrey S Berger, Juuso I Blomster, F Gerry R Fowkes, W Schuyler Jones, Brian G Katona, Kenneth W Mahaffey, Lars Norgren, Frank W Rockhold and William R Hiatt in Vascular Medicine</p
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