Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Canas, Paula M.; Duarte, João M. N.; Rodrigues, Ricardo J.; Köfalvi, Attila; Cunha, Rodrigo A.

doi:10.1016/j.neurobiolaging.2008.01.003

Cited by 125 publications

(97 citation statements)

References 52 publications

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“…In line with this, age-dependent reduction in the density of synaptic proteins were reported in the rodent brain, namely SNARE complex proteins, vesicle-mobilizing proteins, vesicular neurotransmitter transporters, postsynaptic proteins, and components of the synaptic vesicle cycle (Canas et al, 2009;VanGuilder et al, 2010), which can contribute to the hippocampal function decline and thus to reduction of memory performance (Allard et al, 2012;Gage et al, 1984a;Kennard and Woodruff-Pak, 2011;Pistell et al, 2012).…”

Section: Discussionsupporting

confidence: 53%

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

Duarte

Gruetter

2014

Neurobiology of Aging

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H MRS Brain Metabolism a b s t r a c tAlterations to brain homeostasis during development are reflected in the neurochemical profile determined noninvasively by 1 H magnetic resonance spectroscopy. We determined longitudinal biochemical modifications in the cortex, hippocampus, and striatum of C57BL/6 mice aged between 3 and 24 months . The regional neurochemical profile evolution indicated that aging induces general modifications of neurotransmission processes (reduced GABA and glutamate), primary energy metabolism (altered glucose, alanine, and lactate) and turnover of lipid membranes (modification of choline-containing compounds and phosphorylethanolamine), which are all probably involved in the frequently observed age-related cognitive decline. Interestingly, the neurochemical profile was different in male and female mice, particularly in the levels of taurine that may be under the control of estrogen receptors. These neurochemical profiles constitute the basal concentrations in cortex, hippocampus, and striatum of healthy aging male and female mice.

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Section: Discussionsupporting

confidence: 53%

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

Duarte

Gruetter

2014

Neurobiology of Aging

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“…Interestingly, we failed to identify diabetes-induced neuronal loss in brain sections stained either cresyl violet or FluoroJade-C, which was corroborated by the lack of altered microtubuleassociated protein 2 (MAP2) immunoreactivity, a marker of neuronal density [95]. This indicates that T2D primarily causes synaptic deterioration without neuronal death, which resembles the events occurring in aging [128] and models mimicking early AD [129,130], thus corroborating the association of insulin resistance and T2D with increased incidence of AD. Moreover, compared to non-diabetic Wistar rats, also non-obese insulin-resistant Goto-Kakizyki (GK) rats displayed reduced spatial memory, which was accompanied by reduced pre-synaptic markers and increased glial specific proteins in the hippocampus [131].…”

Section: Insulin-resistant Diabetesmentioning

confidence: 56%

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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“…A similar decrease in both CB1 receptor binding and mRNA levels was found in most of the basal ganglia in rats during ageing [223]. Also, in isolated rat hippocampal synaptosomes, a reduction in CB1 receptor densities in ageing was described [224]. On the contrary, Liu et al [225] found no differences in CB1 receptor protein levels between four-and 24-month-old rats in the hippocampus.…”

Section: Cannabinoid System May Change During Ageing In the Brainmentioning

confidence: 67%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

121

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Cited by 125 publications

References 52 publications

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

The endocannabinoid system in normal and pathological brain ageing

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