Differential effects of type 2 diabetes on brain glycometabolism in rats: focus on glycogen and monocarboxylate transporter 2

Shima, Takeru; Jesmin, Subrina; Matsui, Takashi; Soya, Mariko; Soya, Hideaki

doi:10.1007/s12576-016-0508-6

Cited by 22 publications

(20 citation statements)

References 23 publications

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“…16,17 MCT4 expression is not altered. 16 The effect on GLUT1 seems inconsistent, with some studies reporting upregulation and others finding no alteration. 46,47 Similar to the results of the present study, MCT1 expression is upregulated and GLUT3 expression remains unaltered in the mature hippocampus.…”

Section: Discussionmentioning

confidence: 89%

“…Oxidative stress and inflammation may negatively influence hippocampal dendritogenesis and function. Furthermore, in adult rats, hyperglycemia alters glycogen and lactate metabolism in the hippocampus . Astrocytic glycogen breakdown and astrocyte‐neuron‐lactate transport has an important role in hippocampal synaptic morphology and plasticity …”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, in adult rats, hyperglycemia alters glycogen and lactate metabolism in the hippocampus. 16,17 Astrocytic glycogen breakdown and astrocyte-neuron-lactate transport has an important role in hippocampal synaptic morphology and plasticity. [18][19][20] The objective of the present study was to determine the long-term effects of recurrent neonatal hyperglycemia of graded severity on hippocampal neurochemical profile and dendritic structure in rats.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus

et al. 2018

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Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214.6 ± 11.6 mg/dL; severe hyperglycemia (severe-HG), 338.9 ± 21.7 mg/dL; control, 137.7 ± 2.6 mg/dL) was induced from postnatal day (P) 3 to P12. On P30, the hippocampal neurochemical profile was determined using in vivo H MR spectroscopy. Dendritic arborization in the hippocampal CA1 region was determined using microtubule-associated protein (MAP)-2 immunohistochemistry. In Experiment 2, continuous hyperglycemia (mean blood glucose 275.3 ± 25.8 mg/dL; control, 142.3 ± 2.6 mg/dL) was induced from P2 to P6 by injecting streptozotocin (STZ) on P2. The mRNA expression of glycogen synthase 1 (Gys1), lactate dehydrogenase (Ldh), glucose transporters 1 (Glut1) and 3 (Glut3) and monocarboxylate transporters 1 (Mct1), 2 (Mct2) and 4 (Mct4) in the hippocampus was determined on P6. In Experiment 1, MRS demonstrated lower lactate concentration and glutamate/glutamine (Glu/Gln) ratio in the severe-HG group, compared with the control group (p< 0.05). Phosphocreatine/creatine ratio was higher in both hyperglycemia groups (p < 0.05). MAP-2 histochemistry demonstrated longer apical segment length, indicating abnormal synaptic efficacy in both hyperglycemia groups (p < 0.05). Experiment 2 showed lower Glut1, Gys1 and Mct4 expression and higher Mct1 expression in the hyperglycemia group, relative to the control group (p < 0.05). These results suggest that hyperglycemia alters substrate transport, lactate homeostasis, dendritogenesis and Glu-Gln cycling in the developing hippocampus. Abnormal neurochemical profile and dendritic structure due to hyperglycemia may partially explain the long-term hippocampus-mediated cognitive deficits in human ELGANs.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus

et al. 2018

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“…The literature on brain glycogen in diabetes is somewhat confounding. For instance, a rat model of type 2 diabetes (Otsuka Long-Evans Tokushima Fatty rat: OLETF) have been reported to accumulate ~30% higher amounts of glycogen in the hippocampus (Shima et al, 2017) while brain stem glycogen levels remain similar (Shima, Jesmin, Matsui, Soya, & Soya, 2018). Another type 2 diabetes model rat strain (Zucker Diabetic Fatty rat: ZDF) was reported to have a tendency for decreased hippocampal glycogen levels (Shima et al, 2017;Sickmann, Waagepetersen, Schousboe, Benie, & Bouman, 2010).…”

Section: ;mentioning

confidence: 99%

Glycogen distribution in mouse hippocampus

Hirase

Akther

Wang

et al. 2019

J of Neuroscience Research

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The hippocampus is a limbic structure involved in the consolidation of episodic memory. In the recent decade, glycogenolysis in the rodent hippocampus has been shown critical for synaptic plasticity and memory formation. Astrocytes are the primary cells that store glycogen which is subject to degradation in hypoglycemic conditions. Focused microwave application to the brain halts metabolic activities, and therefore preserves brain glycogen. Immunohistochemistry against glycogen on focused microwave‐assisted brain samples is suitable for both macroscopic and microscopic investigation of glycogen distribution. Glycogen immunohistochemistry in the hippocampus showed a characteristic punctate signal pattern that depended on hippocampal layers. In particular, the hilus is the most glycogen‐rich subregion of the hippocampus. Moreover, large glycogen puncta (>0.5 µm in diameter) observed in neuropil areas are organized in a patchy pattern consisting of puncta‐rich and ‐poor astrocytes. These observations are discussed with respect to distinct hippocampal neural activity states observed in live animals.

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“…Exercise results in increased serotonin turnover, which may promote glycogenolysis (Matsui et al, 2015). The same group have reported that type 2 diabetic patients had higher glycogen in the hippocampus, hypothalamus and cortex, and that MCT2 protein levels decreased, suggesting less efficient lactate shuttling (Shima et al, 2016). This effect has been correlated with exercise, which was shown to increase glycogen levels, MCT2 expression and improve cognitive performance.…”

Section: Glycogen and Exercisementioning

confidence: 99%

Emerging Roles for Glycogen in the CNS

Waitt

Reed

Ransom

et al. 2017

Front. Mol. Neurosci.

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The ability of glycogen, the depot into which excess glucose is stored in mammals, to act as a source of rapidly available energy substrate, has been exploited by several organs for both general and local advantage. The liver, expressing the highest concentration of glycogen maintains systemic normoglycemia ensuring the brain receives a supply of glucose in excess of demand. However the brain also contains glycogen, although its role is more specialized. Brain glycogen is located exclusively in astrocytes in the adult, with the exception of pathological conditions, thus in order to benefit neurons, and energy conduit (lactate) is trafficked inter-cellularly. Such a complex scheme requires cell type specific expression of a variety of metabolic enzymes and transporters. Glycogen supports neural elements during withdrawal of glucose, but once the limited buffer of glycogen is exhausted neural function fails and irreversible injury ensues. Under physiological conditions glycogen acts to provide supplemental substrates when ambient glucose is unable to support function during increased energy demand. Glycogen also supports learning and memory where it provides lactate to neurons during the conditioning phase of in vitro long-term potentiation (LTP), an experimental correlate of learning. Inhibiting the breakdown of glycogen or intercellular transport of lactate in in vivo rat models inhibits the retention of memory. Our current understanding of the importance of brain glycogen is expanding to encompass roles that are fundamental to higher brain function.

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Differential effects of type 2 diabetes on brain glycometabolism in rats: focus on glycogen and monocarboxylate transporter 2

Cited by 22 publications

References 23 publications

Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus

Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus

Glycogen distribution in mouse hippocampus

Emerging Roles for Glycogen in the CNS

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