Medial forebrain bundle stimulation in rats activates glycogen phosphprylase in layers 4, 5b and 6 of ipsilateral granular neocortex

Harley, Carolyn W.; Milway, J. Stephen; Fara-On, Maria

doi:10.1016/0006-8993(95)00481-5

Cited by 17 publications

(10 citation statements)

References 39 publications

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“…Moreover, blockade of brain glucose transport or astrocytic glucose metabolism inhibits memory consolidation (see [37] and references therein). In line with this, somatosensory stimulation increases the rate of glycogenolysis [38,39] and thus reduces brain glycogen levels [40,41], the glucose storage in the brain. Thus, impaired brain glucose homeostasis may compromise learning processes and memory consolidation, and this could constitute a link between diabetes and brain alterations leading to encephalopathy.…”

Section: Brain Metabolism and Cognitive Performancementioning

confidence: 62%

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Duarte¹

2014

aging dis

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From epidemiological studies it is known that diabetes patients display increased risk of developing dementia. Moreover, cognitive impairment and Alzheimer's disease (AD) are also accompanied by impaired glucose homeostasis and insulin signalling. Although there is plenty of evidence for a connection between insulin-resistant diabetes and AD, definitive linking mechanisms remain elusive. Cerebrovascular complications of diabetes, alterations in glucose homeostasis and insulin signalling, as well as recurrent hypoglycaemia are the factors that most likely affect brain function and structure. While difficult to study in patients, the mechanisms by which diabetes leads to brain dysfunction have been investigated in experimental models that display phenotypes of the disease. The present article reviews the impact of diabetes and AD on brain structure and function, and discusses recent findings from translational studies in animal models that link insulin resistance to metabolic alterations that underlie brain dysfunction. Such modifications of brain metabolism are likely to occur at early stages of neurodegeneration and impact regional neurochemical profiles and constitute non-invasive biomarkers detectable by magnetic resonance spectroscopy (MRS).Key words: Neurodegeneration, Diabetes, Alzheimer's disease, Insulin, Metabolism Diabetes mellitus can be defined as a chronic metabolic disorder characterized by hyperglycaemia, resulting from inappropriate insulin secretion and/or action [1]. The vast majority of the diabetes cases are included in two main categories, classified according to the underlying cause, which are type 1 diabetes (T1D) or insulindependent diabetes, generally caused by an autoimmune reaction to antigens of pancreatic β-cells, leading to impaired insulin production, and type 2 diabetes (T2D) or insulin-resistant diabetes, characterised by inefficiency of insulin action. While T1D is mainly observed in children and adolescents, T2D is more common among adults, accounting for more than 90% of the diabetes cases worldwide. The prevalence of diabetes and impaired glucose tolerance achieved now epidemic proportions, respectively at 6.9% and 8.3% of the world population, and predicted to raise to 8. 0% and 10.1% in 2035 [2]. Moreover, diabetes is nowadays a leading cause of death accounting for 8.4% of global mortality in people aged between 20 and 79 years [2]. The main contributor for the high prevalence of diabetes is the rise of obesity, related to the combination of ample food availability and a sedentary lifestyle, contrasting to less abundant food supplies and higher physical activity observed until a century ago.Diabetes is associated with the occurrence of well described microvascular complications that affect different organs, leading most commonly to retinopathy, nephropathy and peripheral neuropathy, which development is dependent on the duration of the disease and glycaemia control [3]. When the control of the disorder allowed patients to live longer and without these Volume 6, N...

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Section: Brain Metabolism and Cognitive Performancementioning

confidence: 62%

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Duarte¹

2014

aging dis

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“…(i) Glycogen phosphorylase can be activated within seconds by conversion from the inactive b‐form to the active a‐form (Folbergrova et al. 1978), and its activation occurs during behavioral activities, including intracranial reward self‐stimulation and exposure to a novel environment (Harley et al. 1995; Konkle et al.…”

Section: Discussionmentioning

confidence: 99%

“…Brain glycogen is often considered to be a slowly turning over emergency fuel reservoir, but many lines of evidence indicate that glycogen is tapped for fuel without overt or prolonged energy deficits. (i) Glycogen phosphorylase can be activated within seconds by conversion from the inactive bform to the active a-form (Folbergrova et al 1978), and its activation occurs during behavioral activities, including intracranial reward self-stimulation and exposure to a novel environment (Harley et al 1995;Konkle et al 1999;Konkle and Bielajew 2004;Walling et al 2006). (ii) Glycogenolysis in cultured astrocytes and brain slices assayed in vitro under normoglycemic conditions is initiated by many signals arising from neuronal activity, including the wide-spread locus coeruleus noradrenergic arousal-stress-response systems, diverse neurotransmitter systems and specific electrolytes (Magistretti et al 1981;Hof et al 1988;Hertz and Peng 1992;Stone 1994;Dienel and Cruz 2006;Hertz et al 2007).…”

Section: Physiological Roles Of Glycogen In Activated Astrocytesmentioning

confidence: 99%

A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover

Dienel

Ball

Cruz

2007

Journal of Neurochemistry

117

147

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Glycogen is degraded during brain activation but its role and contribution to functional energetics in normal activated brain have not been established. In the present study, glycogen utilization in brain of normal conscious rats during sensory stimulation was assessed by three approaches, change in concentration, release of 14 C from pre-labeled glycogen and compensatory increase in utilization of blood glucose (CMR glc ) evoked by treatment with a glycogen phosphorylase inhibitor. Glycogen level fell in cortex, 14 C release increased in three structures and inhibitor treatment caused regionally selective compensatory increases in CMR glc over and above the activation-induced rise in vehicle-treated rats. The compensatory rise in CMR glc was highest in sensory-parietal cortex where it corresponded to about half of the stimulus-induced rise in CMR glc in vehicle-treated rats; this response did not correlate with metabolic rate, stimulus-induced rise in CMR glc or sequential station in sensory pathway. Thus, glycogen is an active fuel for specific structures in normal activated brain, not simply an emergency fuel depot and flux-generated pyruvate greatly exceeded net accumulation of lactate or net consumption of glycogen during activation. The metabolic fate of glycogen is unknown, but adding glycogen to the fuel consumed during activation would contribute to a fall in CMR O2 / CMR glc ratio. Keywords: brain activation, brain imaging, energetics, glucose utilization, glycogenolysis, sensory stimulation. The importance of quantifying metabolic fluxes induced by brain activation at a cellular level is emphasized by positron emission tomographic, magnetic resonance spectroscopic (MRS) and optical (infrared or fluorescence) studies of brain function in health and disease that rely on measurement of signals generated from endogenous or exogenous tracers metabolized by energy-producing pathways. Astrocytes are increasingly recognized as having essential roles in both signaling and energetics during brain activation, including modulation of neurotransmission via gliotransmitters, synthesis and cycling of amino acid neurotransmitters, regulation of extracellular glutamate and K + levels and blood flow

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“…Brain glycogen content was suggested to increase with circulating insulin and with brain glucose concentration (152, 153, 157–159). While glycogen content is increased under anesthesia (152, 160, 161), somatosensory stimulation increases glycogenolysis rate (162, 163) and thus reduces brain glycogen levels (164, 165). Although suggesting a direct role of glycogen metabolism in brain function, this was not observed under visual stimulation in both rodents (165) and humans (143).…”

Section: Glycogen Metabolismmentioning

confidence: 99%

Metabolic Flux and Compartmentation Analysis in the Brain In vivo

2013

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Through significant developments and progresses in the last two decades, in vivo localized nuclear magnetic resonance spectroscopy (MRS) became a method of choice to probe brain metabolic pathways in a non-invasive way. Beside the measurement of the total concentration of more than 20 metabolites, 1H MRS can be used to quantify the dynamics of substrate transport across the blood-brain barrier by varying the plasma substrate level. On the other hand, 13C MRS with the infusion of 13C-enriched substrates enables the characterization of brain oxidative metabolism and neurotransmission by incorporation of 13C in the different carbon positions of amino acid neurotransmitters. The quantitative determination of the biochemical reactions involved in these processes requires the use of appropriate metabolic models, whose level of details is strongly related to the amount of data accessible with in vivo MRS. In the present work, we present the different steps involved in the elaboration of a mathematical model of a given brain metabolic process and its application to the experimental data in order to extract quantitative brain metabolic rates. We review the recent advances in the localized measurement of brain glucose transport and compartmentalized brain energy metabolism, and how these reveal mechanistic details on glial support to glutamatergic and GABAergic neurons.

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Medial forebrain bundle stimulation in rats activates glycogen phosphprylase in layers 4, 5b and 6 of ipsilateral granular neocortex

Cited by 17 publications

References 39 publications

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover

Metabolic Flux and Compartmentation Analysis in the Brain In vivo

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