Dataset Information

Adiponectin and Cognitive Decline.

ABSTRACT: Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Initially, it was thought that the main role was only the metabolism control. Later, ADPN receptors were also found in the central nervous system (CNS). In fact, the receptors AdipoR1 and AdipoR2 are expressed in various areas of the brain, including the hypothalamus, hippocampus, and cortex. While AdipoR1 regulates insulin sensitivity through the activation of the AMP-activated protein kinase (AMPK) pathway, AdipoR2 stimulates the neural plasticity through the activation of the peroxisome proliferator-activated receptor alpha (PPAR?) pathway that inhibits inflammation and oxidative stress. Overall, based on its central and peripheral actions, ADPN appears to have neuroprotective effects by reducing inflammatory markers, such as C-reactive protein (PCR), interleukin 6 (IL6), and Tumor Necrosis Factor a (TNFa). Conversely, high levels of inflammatory cascade factors appear to inhibit the production of ADPN, suggesting bidirectional modulation. In addition, ADPN appears to have insulin-sensitizing action. It is known that a reduction in insulin signaling is associated with cognitive impairment. Based on this, it is of great interest to investigate the mechanism of restoration of the insulin signal in the brain as an action of ADPN, because it is useful for testing a possible pharmacological treatment for the improvement of cognitive decline. Anyway, if ADPN regulates neuronal functioning and cognitive performances by the glycemic metabolic system remains poorly explored. Moreover, although the mechanism is still unclear, women compared to men have a doubled risk of developing cognitive decline. Several studies have also supported that during the menopausal transition, the estrogen reduction can adversely affect the brain, in particular, verbal memory and verbal fluency. During the postmenopausal period, in obese and insulin-resistant individuals, ADPN serum levels are significantly reduced. Our recent study has evaluated the relationship between plasma ADPN levels and cognitive performances in menopausal women. Thus, the aim of this review is to summarize both the mechanisms and the effects of ADPN in the central nervous system and the relationship between plasma ADPN levels and cognitive performances, also in menopausal women.

SUBMITTER: Rizzo MR

PROVIDER: S-EPMC7139651 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Adiponectin and Cognitive Decline.

Rizzo Maria Rosaria MR Fasano Renata R Paolisso Giuseppe G

International journal of molecular sciences 20200316 6

Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Initially, it was thought that the main role was only the metabolism control. Later, ADPN receptors were also found in the central nervous system (CNS). In fact, the receptors AdipoR1 and AdipoR2 are expressed in various areas of the brain, including the hypothalamus, hippocampus, and cortex. While AdipoR1 regulates insulin sensitiv ...[more]

PMID: 32188008

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Project description:Recent microarray studies in the hippocampus of rodents or Alzheimerâs disease (AD) subjects have identified a substantial number of cellular pathways/processes correlated with aging and cognitive decline. However, the temporal relationships among these expression changes or with cognitive impairment have not been studied in depth. Here, using Affymetrix microarrays, immunohistochemistry and Morris water maze cognitive testing across 5 age groups of male F344 rats (n=9-15/group, one microarray per animal), we systematically analyzed the temporal sequence and cellular localization of aging changes in expression. These were correlated with performance scores on the hippocampus-dependent Morris Water Maze task. 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Evidence of cognitive impairment first appeared in the 12-month-old group (midlife) and was increased further in the 23-month-old group, exhibiting the highest correlations with some upregulated genes related to cholesterol transport (e.g., Apoe, Abca2), protein management and ion binding. Some upregulated genes for inflammation (Il6st) and myelinogenesis (Pmp22) also correlated with impairment. Together, the data are consistent with a novel sequential cascade model of brain aging in which metabolic alterations early in maturity are followed by inflammation and midlife activation of an astrocyte-centered cholesterol trafficking pathway that stimulates oligodendrocyte remyelination programs. Importantly, this cholesterol trafficking pathway also may compete for astroglial bioenergetic support of neurons, in turn, leading to downregulation of energy-dependent pathways needed to sustain cognitive functions. Experiment Overall Design: Fisher 344 rats aged 3 (n = 9), 6 (n = 9), 9 (n = 9), 12 (n = 9), or 25 (n = 15; but see below) months were behaviorally characterized on the Morris water maze. Briefly, animals were placed in a circular water bath chamber with a partially submerged platform. Three times per day for three days, animals were placed at randomized starting points with the goal of locating the hidden platform. Generally, animals became better at locating the platform, and by the third day of training, were reliably swimming directly to the platform despite randomized starting loci. On the fourth day, the platform was removed and the degree to which the animals focused their searches on the area that previously contained the platform was measured. On the last day of behavior, animals were given a cue trial in which the platform was raised above the water level so that the rats could see it. Measures taken from the behavior study included path length (how long did the animal swim prior to locating the platform/ platform area), latency to platform in seconds, and velocity (centimeters/ second; swim speed). Two aged animals (E2 and E12) were removed from the study for poor health, reducing the 23 month cohort (n = 13). Twelve to twenty four hours after the last behavioral session, animals were killed and their hippocampi removed. The right hippocampus went to immunohistochemistry for quantification and localization of selected protein products. The left hippocampus was dissected, the CA1 region removed and frozen in dry ice prior to microarray processing. mRNA was extracted from each animal's tissue by standard Affymetrix protocols (see Blalock et al., 2003) and hybridized to individual microarrays (RAE 230A; N = 49 arrays in total). Results were processed with the MAS5 algorithm and subjected to âall probe setâ scaling with a target intensity of 500. Probe sets were filtered for presence (> = 5 presence calls study wide) and gene symbol level annotation prior to statistical analysis. 1-ANOVA across age was used to identify aging-related probe sets/genes (p <= 0.05). Aging-related genes were subjected to post hoc template correlation to determine the pattern of age-related change, and further, within the 12 and 23 month old groups, Pearson's correlation with behavioral scores was used to identify genes whose expression levels correlated significantly (p <= 0.05) with behavior. Twelve and 23 month old groups were chosen for this correlation analysis as they showed the greatest variability among similarly aged animals, suggesting that these ages show important cognitive transition phases during aging-related cognitive decline. Functional grouping analysis was performed using the DAVID suite of on-line tools.

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Dataset Information

Adiponectin and Cognitive Decline.

Publications

Adiponectin and Cognitive Decline.

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