Glucose Metabolism and Acetylcholine Synthesis in Relation to Neuronal Activity in Alzheimer's Disease

Sims, Neil R.; Smith, Christopher; Davison, Alan; Bowen, David M.; Flack, R. H. A.; Snowden, Julie S.; Neary, David

doi:10.1016/s0140-6736(80)90884-3

Cited by 185 publications

(59 citation statements)

References 20 publications

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“…), especially visual attention. [2][3][4] A CRT, one of the parameters in the CRT task, has been used as a useful psychometric index of mental performance in human clinical studies. 2,4) Experimental evidence that a functional relation between CRT shortening and the regulation of selective attention exists has been accumulating.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] A CRT, one of the parameters in the CRT task, has been used as a useful psychometric index of mental performance in human clinical studies. 2,4) Experimental evidence that a functional relation between CRT shortening and the regulation of selective attention exists has been accumulating. 3,6,11) On the other hand, the CRT has also been valuable in evaluating the role of basal ganglia in motor programming and response output, both in human diseases such as Parkinson's and Huntington's and in animal studies involving experimental disruption of the neostriatum and its connections.…”

Section: Discussionmentioning

confidence: 99%

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The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

Mishima

Fujii

Aoo

et al. 2002

Biological & Pharmaceutical Bulletin

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Information processes through the learning and memory system consist of three steps: attention (arousal, decisionmaking, motivation, etc.); short-term memory (working memory); and long-term memory (reference memory).1) Attention is used in experimental and human clinical studies to mean the ability to perceive or focus on certain stimuli, but to ignore others in the environment. When people and animals are confronted with a stimulus in the environment, they must usually decide whether they need to remember it and they memorize it as a part of two memory systems (short-term memory and long-term memory) through attentional processes if necessary. Thus most investigators have found that this mechanism plays an important role in information processing and memory processing.A choice reaction time (CRT) task has been regarded as a good measure in experimental and human clinical studies on cognitive performance capability (attention, arousal, decision-making, motivation, etc.), especially visual attention. 2-4)The pioneering work of the group of Robbins in attentional processes using a five-choice serial reaction time task has shown that cholinergic innervation of the forebrain is important in attentional processes, noradrenergic innervation permits accurate performance during arousing situations, dopaminergic innervation of the nucleus accumbens is involved in behavioral activation, and forebrain serotonin (5-HT) is involved in the control of impulsive behavior. [5][6][7][8][9][10] We also reported that ischemic-hypoxic insult to neonatal rats and methamphetamine produced severe impairment of attention in a two-lever correct response (CR) task.11,12) Although a variety of neurons and neurotransmitters have thus been implicated in attentional processes in the five-choice serial reaction time task, the pharmacological characterization in the attentional processes of a two lever CRT task is not understood well. The objective of the present study was to investigate the pharmacological characterization in the attentional processes of a two-lever CRT task using 10 different centrally acting drugs: scopolamine, a nonselective muscarinic receptor antagonist; methamphetamine, a psychostimulant; D 9 -tetrahydrocannabinol (THC), the major psychoactive component of marijuana; prazosin, a noradrenergic a 1 receptor antagonist; 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT), a selective 5-HT 1A receptor agonist; muscimol, a GABA A receptor agonist; dizocilpine (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist; 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride (YM90K), an alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor antagonist; N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor; and nilvadipine, an L-type Ca 2ϩ channel blocker. MATERIALS AND METHODS AnimalsMale Wistar rats weighing 200-250 g were obtained from the Kyu-Do Co., Ltd. (Saga, Japan), and were housed in groups of 4 to 5 per cage, in a room with a controlled temperature of 23Ϯ2°...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

Mishima

Fujii

Aoo

et al. 2002

Biological & Pharmaceutical Bulletin

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“…Insulin/IGF resistance, oxidative stress, and metabolic dysfunction in AD Deficits in cerebral glucose utilization and energy metabolism occur very early in the course of AD (Iwangoff, Armbruster et al 1980;Sims, Bowen et al 1980;. Glucose uptake and utilization in brain are dependent upon glucose transport by glucose transporter 4 (GLUT4), which is stimulated by insulin.…”

Section: Insulin/igf Resistance and Amyloid-beta (Aβ) Accumulation Anmentioning

confidence: 99%

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

Monte¹,

Tong²,

Wands³

2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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“…Deficits in cerebral glucose utilization and energy metabolism occur early in AD, either prior to, or coincident with initial stages of cognitive decline (22,131,132). Correspondingly, impairments in brain insulin and IGF signaling mechanisms correlate with severity of AD (6).…”

Section: Stress Factors In the Pathogenesis Of Brain Insulin Resistancementioning

confidence: 99%

Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease

Monte

2012

Front Biosci

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Growing evidence supports roles for brain insulin and insulin-like growth factor (IGF) resistance and metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). Whether the underlying problem stems from a primary disorder of central nervous system (CNS) neurons and glia, or secondary effects of systemic diseases such as obesity, Type 2 diabetes, or metabolic syndrome, the end-results include impaired glucose utilization, mitochondrial dysfunction, increased oxidative stress, neuroinflammation, and the propagation of cascades that result in the accumulation of neurotoxic misfolded, aggregated, and ubiquitinated fibrillar proteins. This article reviews the roles of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism, and discusses therapeutic strategies and lifestyle approaches that could be used to prevent, delay the onset, or reduce the severity of AD. Finally, it is critical to recognize that AD is heterogeneous and has a clinical course that fully develops over a period of several decades. Therefore, early and multi-modal preventive and treatment approaches should be regarded as essential. KeywordsAmyloid; Anti-oxidants; Brain diabetes; Brain insulin resistance; Incretins; Insulin; Insulin sensitizers; Liver-Brain-Axis; Metal Chelation; Neuroprotection; Nitrosamine; Oxidative Stress; Polyphenols; Statins; Streptozotocin; Tau; Type 3 diabetes INTRODUCTIONThe gold standard for definitively diagnosing AD is to perform a postmortem examination of the brain, with the objective of demonstrating beyond-normal aging associated densities of neurofibrillary tangles, neuritic plaques, and amyloid-beta 40-42 kD fragments of amyloid beta precursor protein (AβPP-Aβ) deposits in corticolimbic structures, bearing in mind that neurodegeneration frequently involves multiple other cortical regions as well. The common thread among these characteristic lesions is that they harbor insoluble aggregates of abnormally phosphorylated and ubiquitinated tau, and neurotoxic AβPP-Aβ in the form of Send correspondence to: Suzanne M. de la Monte, Rhode Island Hospital, 55 Claverick Street, Room 419, Providence, RI. 02903, Tel: 401-444-7364, Fax: 401-444-2939, Suzanne_DeLaMonte_MD@Brown.edu. HHS Public Access Author manuscriptFront Biosci (Elite Ed). Author manuscript; available in PMC 2015 August 26. Published in final edited form as:Front Biosci (Elite Ed). ; 4: 1582-1605. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript oligomers, fibrillar aggregates, or extracellular plaques. Secreted AβPP-Aβ oligomers have been demonstrated to be neurotoxic and to inhibit hippocampal long-term potentiation, i.e. synaptic plasticity (1).To improve diagnosis and treatment, we must learn to connect the development and progression of neurodegeneration with molecular, biochemical, physiological, neuroimaging, and clinical abnormalities in AD. Several strategies could be taken to advance this proc...

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Glucose Metabolism and Acetylcholine Synthesis in Relation to Neuronal Activity in Alzheimer's Disease

Cited by 185 publications

References 20 publications

The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease

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