Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease

Penner, Jacob; Rupsingh, Raul; Smith, Morgan; Wells, Jennie; Borrie, Michael; Bartha, Robert

doi:10.1016/j.pnpbp.2009.10.007

Cited by 54 publications

(42 citation statements)

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“…Decreased glutamate levels were recently reported in the brain of AD patients [56]. In addition, Penner et al found that glutamate concentration was increased in the Aging and Disease • Volume 6, Number 5, October 2015 307 right hippocampus of AD patients after four months of galantamine treatment relative to pre-treatment levels, and those variations in glutamate levels were related to variations in N-acetylaspartate (NAA) content and cognitive performance [57]. Interestingly, it has been recurrently demonstrated that the regional levels of NAA and glutamate in the brain are positively associated since both are mainly located within neuronal cells (see [43] and references there in).…”

Section: Brain Metabolism In Admentioning

confidence: 96%

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 In Admentioning

confidence: 96%

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Duarte¹

2014

aging dis

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“…For example, a transient increase in tNAA concentration was associated with short-term functional response during donepezil treatment in Alzheimer disease, suggesting that tNAA also reflects functional integrity and recovery (137). Other studies have shown a decreased mIns/tCr ratio following donepezil treatment (138) and an increased Glu level after galantamine treatment for Alzheimer disease (139).…”

Section: Special Review: Clinical Proton Mr Spectroscopy In Central Nmentioning

confidence: 99%

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Öz¹,

Alger²,

Barker³

et al. 2014

Radiology

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540

356

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A large body of published work shows that proton (hydrogen 1 [ 1 H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1 H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1 H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1 H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.q RSNA, 2014 Online supplemental material is available for this article. G.O. (e-mail: gulin@cmrr.umn.edu). 2 The complete list of authors and affiliations is at the end of this article.q RSNA, 2014 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. Radiology H MR Spectrum of the Brain: Metabolites and Their Biomarker PotentialMR spectroscopy provides a very different basic "readout" than MR imaging, namely a spectrum rather than an techniques were developed. These early localization techniques included pointresolved spectroscopy (PRESS) (1,2) and stimulated echo acquisition mode (STEAM) (3), methods that are now widely used in clinical MR spectroscopy applications.Preliminary studies revealed large differences in metabolite levels in acute stroke (4), chronic multiple sclerosis (5), and brain tumors compared with healthy brain (6). Although this work stimulated a surge of interest in 1 H MR spectroscopy for diagnosing and assessing CNS disorders during the early days of the "Decade of the Brain" (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999), many suboptimal patient studies (7) and the lack of consistent guidelines have led to a situation where, 20 years later, MR spectroscopy is still considered an "investigational technique" by some medical professionals and health care organizations. However, the ability to make an early, noninvasive diagnosis or to increase confidence in a suspected diagnosis is highly valued by patients and clinicians alike. As a result, an increasing number of imaging centers are incorporating MR spectroscopy into their clinical protocols for brain...

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“…Thus, it is likely that the reversal of kynurenic acidinduced suppression of glutamatergic neurotransmission by galantamine may be responsible for its clinical effect in schizophrenia. Penner et al (61) have more recently showed using proton magnetic resonance spectroscopy ( 1 H MRS) that four months of galantamine treatment, which consisted of an 8 mg daily dose for the first month and a 16 mg daily dose for the remaining three months, increased absolute glutamate levels and the ratio of glutamate to creatine in the right hippocampus of patients with Alzheimer's disease. They also demonstrated that the changes were associated with the increased cognitive performance in patients.…”

Section: Glutamate and γ-Aminobutyric Acid (Gaba)mentioning

confidence: 99%

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

et al. 2011

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Abstract. Several lines of evidence suggest that cholinergic deficits may contribute to the pathophysiology of psychiatric disorders as well as Alzheimer's disease. There is growing clinical evidence that galantamine, currently used for the treatment of Alzheimer's disease, may improve cognitive dysfunction and psychiatric illness in schizophrenia, major depression, bipolar disorder, and alcohol abuse. Since galantamine is a rather weak acetylcholinesterase inhibitor, but has additional allosteric potentiating effects at nicotinic receptors, it affects not only cholinergic transmission but also other neurotransmitter systems such as monoamines, glutamate, and γ-aminobutyric acid (GABA) through its allosteric mechanism. It is likely that these effects may result in more beneficial effects. To understand the underlying mechanism for the clinical effectiveness of galantamine, neuropharmacological studies have been performed in animal models of several psychiatric disorders. These studies suggest that not only the nicotinic receptor-modulating properties but also the muscarinic receptor activation contribute to the antipsychotic effect and improvement of cognitive dysfunction by galantamine. This review summaries the current status on the pharmacology of galantamine, focusing on its effect on neurotransmitter release and pharmacological studies in animal models of psychiatric disorders.

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Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease

Cited by 54 publications

References 54 publications

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

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