Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance

Cisternas, Pedro; Salazar, Paulina; Serrano, Felipe; Montecinos-Oliva, Carla; Arredondo, Sebastián B.; Varela-Nallar, Lorena; Barja, Salesa; Vio, Carlos P.; Gómez‐Pinilla, Fernando; Inestrosa, Nibaldo C.

doi:10.1016/j.bbadis.2015.08.016

Cited by 61 publications

(47 citation statements)

References 79 publications

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“…Dietary fructose has emerged as a major contributor to the current epidemic of metabolic disorders [3–7], based on its effects on hepatic de novo lipogenesis, abdominal obesity, cholesterol and insulin resistance [8]. More recently, fructose was found to compromise synaptic plasticity, adult neurogenesis [9], and the capacity of neural circuits to cope with the effects of brain injury [10]. Fructose appears to induce a stage of metabolic dysfunction in the brain, negatively impacting cognitive function [10].…”

Section: Introductionmentioning

confidence: 99%

Biglycan gene connects metabolic dysfunction with brain disorder

Ying

Byun

Meng

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Dietary fructose is a major contributor to the epidemic of diabetes and obesity, and it is an excellent model to study metabolic syndrome. Based on previous studies that Bgn0/− gene occupies a central position in a network of genes in the brain in response to fructose consumption, we assessed the capacity of (Bgn0/−) to modulate the action of fructose on brain and body. We exposed male biglycan knockout mice (Bgn0/−) to fructose for 7 weeks, and results showed that Bgn0/− mice compensated for a decrement in learning and memory performance when exposed to fructose. These results were consistent with an attenuation of the action of fructose on hippocampal CREB levels. Fructose also reduced the levels of CREB and BDNF in primary hippocampal neuronal cultures. Bgn siRNA treatment abolished these effects of fructose on CREB and BDNF levels, in conjunction with a reduction in a fructose-related increase in Bgn protein. In addition, fructose consumption perturbed the systemic metabolism of glucose and lipids, that were also altered in the Bgn0/ mice. Transcriptomic profiling of hypothalamus, hippocampus, and liver supported the regulatory action of Bgn on key molecular pathways involved in metabolism, immune response, and neuronal plasticity. Overall results underscore the tissue-specific role of the extracellular matrix in the regulation of metabolism and brain function, and support Bgn as a key modulator for the impact of fructose across body and brain.

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Section: Introductionmentioning

confidence: 99%

Biglycan gene connects metabolic dysfunction with brain disorder

Ying

Byun

Meng

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Indeed, a high sucrose diet not only promotes obesity, but also may interfere with the anti-inflammatory effects of high n-3 FAs in adipose tissue [22]. This is relevant to patients being treated for breast cancer because our data suggest that this population consumes up to 32% of kilocalories from added sugars (T. Orchard, unpublished data), an amount that equals or exceeds levels found to be harmful in animal models examining neuroinflammation, neurogenesis, and cognition [27–30]. …”

Section: Effects Of Chemotherapy In the Brainmentioning

confidence: 92%

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits

Orchard

Gaudier-Diaz

Weinhold

et al. 2016

Breast Cancer Res Treat

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Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.

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“…2 and 3) (Agrawal and Gomez-Pinilla, 2012). Our research has revealed the harmful impact of fructose on the brain (Agrawal and Gomez-Pinilla, 2012; Cisternas et al, 2015; Gomez-Pinilla, 2008) such that the animals on fructose show impaired memory and learning skills, as well as reductions in proteins re lated to brain plasticity and mitochondrial bioenergetics (Figs. 1–3) (Agrawal and Gomez-Pinilla, 2012).…”

Section: The Threat Of the New Epidemic Of Metabolic Disordersmentioning

confidence: 99%

“…In addition, the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation (LTP) and long-term depression (LTD) was seriously compromised (Cisternas et al, 2015). Fructose exposure also reduced the number of contact zones and the size of postsynaptic densities (PSDs) in the hippocampus, which changes were concomitant to a decrease in hippocampal neurogenesis (Cisternas et al, 2015). The results of these studies challenge the current view that the effects of diet-induced metabolic abnormalities are restricted to the periphery.…”

Section: The Threat Of the New Epidemic Of Metabolic Disordersmentioning

confidence: 99%

“…(B) Fructose treatment also results in memory deficit in the Barnes maze as evidenced by a decrease in latency time to find the escape hole, in proportion to an increase in CREB activation. (C, D) Fructose exposure also reduces hippocampal excitability in the form of long-term potentiation (LTP), and (E, F) synaptic strength or long-term depression (LTD); for reviews see (Cisternas et al, 2015). This information highlight the deleterious effects of metabolic perturbations on the substrates for synaptic plasticity and cognitive function in the brain.…”

Section: Figmentioning

confidence: 99%

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System biology approach intersecting diet and cell metabolism with pathogenesis of brain disorders

Gómez‐Pinilla

Yang

2018

Progress in Neurobiology

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The surge in meals high in calories has prompted an epidemic of metabolic disorders around the world such that the elevated incidence of obese and diabetic individuals is alarming. New research indicates that metabolic disorders pose a risk for neurological and psychiatric conditions including stroke, Alzheimer’s disease, Huntington’s disease, and depression, all of which have a metabolic component. These relationships are rooted to a dysfunctional interaction between molecular processes that regulate energy metabolism and synaptic plasticity. The strong adaptive force of dietary factors on shaping the brain during evolution can be manipulated to trans form the interaction between cell bioenergetics and epigenome with the aptitude to promote long-lasting brain healthiness. A thorough understanding of the association between the broad action of nutrients and brain fitness requires high level data processing empowered with the capacity to integrate information from a multitude of molecular entities and pathways. Nutritional systems biology is emerging as a viable approach to elucidate the multiple molecular layers involved in information processing in cells, tissues, and organ systems in response to diet. Information about the wide range of cellular and molecular interactions elicited by foods on the brain and cognitive plasticity is crucial for the design of public health initiatives for curtailing the epidemic of metabolic and brain disorders.

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Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance

Cited by 61 publications

References 79 publications

Biglycan gene connects metabolic dysfunction with brain disorder

Biglycan gene connects metabolic dysfunction with brain disorder

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits

System biology approach intersecting diet and cell metabolism with pathogenesis of brain disorders

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