Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats.

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective ß3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1ß, and IL-6 gene expression and IL-1ß and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine.

The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.

Alterations in the duodenum myenteric neurons of Wistar ratsafter ingesting of 2, 4 dichlorophenoxyacetic acid

The 2,4 dichlorophenoxyacetic acid (2,4-D) is a systemic herbicide whose effects in animal organic systemshave been examined in previous studies, being the neurotoxicity considered the predominant effect. However,the studies that detect the 2,4-D neurotoxicity have merely focused in the central nervous system, andtherefore, little is known about the effect of this herbicide in the enteric nervous system. This study aimedto verifying the 2,4-D effects on the myenteric neurons in duodenum of Wistar rats. Ten 60-day-old maleWistar rats (Rattus norvegicus) were divided in two groups: control group (C) that did not receive 2,4-D andexperimental group (E) that received 5.0 mg of 2,4-D/kg for 15 days. At the end of experimental period, theanimal were euthanized, the duodenum was collected and processed for NADPH-diaphorase histochemicalanalysis in order to expose the nitrergic myenteric neurons (NADPH-dp). In the light microscopy analysis, thewhole-mount preparation obtained from duodenum of each animal were image-captured in 120 and 40 fields,for quantitative and morphometric analyses of myenteric neurons, respectively. The neuronal density was notaffected when comparing the two groups, but an increase (p > 0.05) of 8.5% was observed in the cell bodyarea of neurons in the E group. In conclusion, the ingestion of 2,4-D at a dosage of 5.0 mg/kg body weightfor 15 days does not change the neuronal density, but promotes the hypertrophy of NADPH-dp myentericneurons in duodenum of the rats of this study.

Effects of the ingestion of 2, 4 Dichlorophenoxyacetic acid on jejunal myenteric neurons in rats

2,4 dichlorophenoxyacetic acid (2,4-D) is a systemic herbicide. The effects of different levels of 2,4-D on some animal organ systems have been examined, but little is known about its role in the enteric nervous system. The purpose of this study was to verify the effects of 2,4-D administration on the density and morphometry of jejunal myenteric neurons in rats. Ten male rats were assigned to control (C) and experimental (E) groups. For 15 days, group E received, via gavage, 5 mg of 2,4-D.kg–1 body weight. On the 16th day, the animals were sacrificed by a lethal dose of thiopental, and the jejunum was removed by laparotomy and used to obtain whole mount preparations for Giemsa staining and NADPH-diaphorase (NADPHd+) histochemistry to identify neurons. The density and cell body area of the myenteric neurons was measured. In the total neuronal population, the neuronal density/mm2 of the jejunum in groups E and C was equivalent, and the cell body area of the rats in group E was lower (p < 0.05) than that of those in group C. For NADPHd+ neurons, the neuronal density did not differ between the groups, although the cell body area was larger (p < 0.05) in group E. It was concluded that even though 2,4-D does not alter the neuronal density in the rat jejunum, it induces cell body atrophy in the general population of neurons and hypertrophy of the NADPHd+ nitric oxide producing neurons without promoting cell death.

Quantification and morphometry of myenteric neurones in the jejunum of Holtzman rats (Rattus norvegicus).

UNLABELLED: With 2 figures and 3 tables SUMMARY: The morphological pattern of the myenteric plexus (MP) is species-specific, and little is known about this pattern in Holtzman rats. The aim of the current experiment was the morphological and quantitative study of myenteric neurones in the Holtzman rat jejunum. Hematoxylin-Eosin and NADH-diaphorase (NADH-dp) staining were used to assess muscular layer thickness, neurone cell body area (CBA) and nuclei area (NA). Muscular layer thickness was found to be 114.77 ± 14.89 µm. Neuronal densities across the subregions of the jejunum were similar: mesenteric, 11.78 ± 2.89/mm(2) ; intermediate, 12.06 ± 2.69/mm(2) ; and antimesenteric, 10.67 ± 1.89/mm(2) . As expected, there was positive correlation between the CBA and NA of 79.19, 79.26 and 78.5% in the mesenteric, intermediate and antimesenteric subregions of the jejunum, respectively. Medium-sized neurones predominated in the ganglionic arrangement of the MP. These results indicate that the NADH-dp myenteric neurones in the jejunum of Holtzman rats are similar in many aspects to those found in the ileum of Holtzman rats and to those found in the small intestine of Wistar rats, including their location, ganglionic disposition and predominance of medium-sized CBA. However, neuronal density in the jejunum is lower than in the ileum. Based on these results showing morphological similarities to the MP of the Wistar rat, the Holtzman strain can be used to investigate the effects of adverse conditions on the morphology of the MP.