scholarly journals An increase in VGF expression through a rapid, transcription-independent, autofeedback mechanism improves cognitive function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Jye Lin ◽  
Yan Zhao ◽  
Zhe Li ◽  
Shuyu Zheng ◽  
Jin-lin Zou ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Memory Performance ◽  
Memory Function ◽  
Critical Role ◽  
General Mechanism ◽  
Memory Training ◽  
Translational Efficiency ◽  
Truncation Mutant ◽  
Reporter Assays ◽  
Dependent Learning

AbstractThe release of neuropeptides from dense core vesicles (DCVs) modulates neuronal activity and plays a critical role in cognitive function and emotion. The granin family is considered a master regulator of DCV biogenesis and the release of DCV cargo molecules. The expression of the VGF protein (nonacronymic), a secreted neuropeptide precursor that also belongs to the extended granin family, has been previously shown to be induced in the brain by hippocampus-dependent learning, and its downregulation is mechanistically linked to neurodegenerative diseases such as Alzheimer’s disease and other mood disorders. Currently, whether changes in translational efficiency of Vgf and other granin mRNAs may be associated and regulated with learning associated neural activity remains largely unknown. Here, we show that either contextual fear memory training or the administration of TLQP-62, a peptide derived from the C-terminal region of the VGF precursor, acutely increases the translation of VGF and other granin proteins, such as CgB and Scg2, via an mTOR-dependent signaling pathway in the absence of measurable increases in mRNA expression. Luciferase-based reporter assays confirmed that the 3′-untranslated region (3′UTR) of the Vgf mRNA represses VGF translation. Consistently, the truncation of the endogenous Vgf mRNA 3′UTR results in substantial increases in VGF protein expression both in cultured primary neurons and in brain tissues from knock in mice expressing a 3′UTR-truncation mutant encoded by the modified Vgf gene. Importantly, Vgf 3′UTR-truncated mice exhibit enhanced memory performance and reduced anxiety- and depression-like behaviors. Our results therefore reveal a rapid, transcription-independent induction of VGF and other granin proteins after learning that are triggered by the VGF-derived peptide TLQP-62. Our findings suggest that the rapid, positive feedforward increase in the synthesis of granin family proteins might be a general mechanism to replenish DCV cargo molecules that have been released in response to neuronal activation and is crucial for memory function and mood stability.

scholarly journals Within-session verbal learning slope is predictive of lifespan delayed recall, hippocampal volume, and memory training benefit, and is heritable

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kristine B. Walhovd ◽  
Anne Cecilie Sjøli Bråthen ◽  
Matthew S. Panizzon ◽  
Athanasia M. Mowinckel ◽  
Øystein Sørensen ◽  
...  
Keyword(s):  
Memory Performance ◽  
Memory Function ◽  
Verbal Learning ◽  
Hippocampal Volume ◽  
Memory Training ◽  
Long Term Memory ◽  
Human Lifespan ◽  
Significant Heritability ◽  
Mri Scans

AbstractMemory performance results from plasticity, the ability to change with experience. We show that benefit from practice over a few trials, learning slope, is predictive of long-term recall and hippocampal volume across a broad age range and a long period of time, relates to memory training benefit, and is heritable. First, in a healthy lifespan sample (n = 1825, age 4–93 years), comprising 3483 occasions of combined magnetic resonance imaging (MRI) scans and memory tests over a period of up to 11 years, learning slope across 5 trials was uniquely related to performance on a delayed free recall test, as well as hippocampal volume, independent from first trial memory or total memory performance across the five learning trials. Second, learning slope was predictive of benefit from memory training across ten weeks in an experimental subsample of adults (n = 155). Finally, in an independent sample of male twins (n = 1240, age 51–50 years), learning slope showed significant heritability. Within-session learning slope may be a useful marker beyond performance per se, being heritable and having unique predictive value for long-term memory function, hippocampal volume and training benefit across the human lifespan.

scholarly journals The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people

2007 ◽  
Vol 98 (5) ◽  
pp. 960-968 ◽  
Author(s):  
Simone J. P. M. Eussen ◽  
Per M. Ueland ◽  
Robert Clarke ◽  
Henk J. Blom ◽  
Willibrord H. L. Hoefnagels ◽  
...  
Keyword(s):  
Executive Function ◽  
Folic Acid ◽  
Cognitive Function ◽  
Controlled Trial ◽  
Memory Performance ◽  
Memory Function ◽  
Double Blind ◽  
Before And After ◽  
Combined Supplementation ◽  
The One

The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 μg cobalamin (vitamin B12), or 1000 μg cobalamin plus 400 μg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36 %, and increased betaine concentrations by 38 %. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0·07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.

scholarly journals The Association of Meteorological Factors with Cognitive Function in Older Adults

2021 ◽  
Vol 18 (11) ◽  
pp. 5981
Author(s):  
Yuehong Qiu ◽  
Kaigong Wei ◽  
Lijun Zhu ◽  
Dan Wu ◽  
Can Jiao
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Urban Areas ◽  
Meteorological Factors ◽  
Meteorological Data ◽  
Memory Performance ◽  
Memory Function ◽  
International Exchange ◽  
Logical Sequence ◽  
Two Factors

Individual and meteorological factors are associated with cognitive function in older adults. However, how these two factors interact with each other to affect cognitive function in older adults is still unclear. We used mixed effects models to assess the association of individual and meteorological factors with cognitive function among older adults. Individual data in this study were from the database of China Family Panel Studies. A total of 3448 older adults from 25 provinces were included in our analysis. Cognitive functions were measured using a memory test and a logical sequence test. We used the meteorological data in the daily climate dataset of China’s surface international exchange stations, and two meteorological factors (i.e., average temperature and relative humidity) were assessed. The empty model showed significant differences in the cognitive scores of the older adults across different provinces. The results showed a main impact of residence (i.e., urban or rural) and a significant humidity–residence interaction on memory performance in older adults. Specifically, the negative association between humidity and memory performance was more pronounced in urban areas. This study suggested that meteorological factors may, in concert with individual factors, be associated with differences in memory function in older adults.

scholarly journals Gender Differences in the Association between Childhood Socioeconomic Status and Cognitive Function in Later Life

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jiyoung Lyu
Keyword(s):  
Gender Differences ◽  
Socioeconomic Status ◽  
Cognitive Function ◽  
Memory Performance ◽  
Memory Function ◽  
Later Life ◽  
Long Term Effects ◽  
Growth Curve Models ◽  
Childhood Socioeconomic Status ◽  
The Impact

Objectives. This study was aimed to explore the gender differences in the association between childhood socioeconomic status (SES) and cognitive function in later life. Methods. Using a nationally representative sample from the Health and Retirement Study, 5,544 females and 3,863 males were analyzed separately. Growth curve models were used to examine memory status and change in memory from 1998 to 2010. Results. The results showed that SES disadvantage in childhood was associated with lower memory at baseline controlling for adult SES and other covariates. In addition, cumulated disadvantage in SES was associated with poor memory in both genders. Statistically, the impact of cumulative SES on memory function at baseline was significantly different by gender. Discussion. These findings suggest that childhood SES has long-term effects on cognitive function among both men and women, and cumulative SES from childhood to adulthood may be more important for men than women with respect to their memory performance.

Effects of Smartphone-based Memory Training for Older Adults with Subjective Memory Complaints

2017 ◽  
Vol 41 (S1) ◽  
pp. S176-S176 ◽  
Author(s):  
M.S. Shin ◽  
S.J. Oh ◽  
S. Seo ◽  
J.H. Lee ◽  
M.J. Song
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Healthy Aging ◽  
Memory Performance ◽  
Memory Function ◽  
Self Report ◽  
Memory Training ◽  
Subjective Memory Complaints ◽  
Subjective Memory ◽  
Memory Complaints

IntroductionBrain health has garnered increasing attention as a requisite condition for healthy aging. The rapid growth in mobile health and increasing smartphone ownership among older adults has paved the way for smartphones to be utilized as effective tools for improving mental fitness.ObjectivesThere are few studies that have explored the efficacy of smartphone-based cognitive training. The present study examined the memory-enhancing effects of smartphone-based memory training for older adults.AimsWe explored whether newly developed application “Smartphone-based brain Anti-aging and memory Reinforcement Training (SMART)” improved memory performance in older adults with subjective memory complaints.MethodsA total of 53 adults (mean age: 59.3 years) were randomised into either one of two smartphone-based intervention groups (SMART vs. Fit Brains®) or a wait-list group. Participants in the intervention groups underwent 15–20 minutes of training per day, five days per week for 8 weeks. We used objective cognitive measures to evaluate changes with respect to four domains: attention, memory, working memory (WM), and executive function (inhibition, fluency, etc.). In addition, we included self-report questionnaires to assess levels of subjective memory complaints.ResultsThe performance on WM test increased significantly in the SMART group (t[17] = 6.27, P < 0.0001) but not in the control groups. Self-reports of memory contentment, however, increased in the Fit Brains® group only (t[18] = 2.12, P = 0.048).ConclusionsUse of an 8-week smartphone-based memory training program may improve working memory function in older adults. However, objective improvement in performance does not necessarily lead to decreased subjective memory complaints.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Inhibition of Hippocampal Aromatization Impairs Spatial Memory Performance in a Male Songbird

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4707-4714 ◽  
Author(s):  
David J. Bailey ◽  
Chunqi Ma ◽  
Kiran K. Soma ◽  
Colin J. Saldanha
Keyword(s):  
Spatial Memory ◽  
Zebra Finch ◽  
Memory Performance ◽  
Memory Function ◽  
Critical Role ◽  
Electrophysiological Response ◽  
Local Inhibition ◽  
Estradiol Synthesis ◽  
Adjacent Brain

Recent studies have revealed the presence and regulation of aromatase at the vertebrate synapse, and identified a critical role played by presynaptic estradiol synthesis in the electrophysiological response to auditory and other social cues. However, if and how synaptic aromatization affects behavior remains to be directly tested. We have exploited 3 characteristics of the zebra finch hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial memory function. Although the zebra finch HP contains abundant aromatase transcripts and enzyme activity, immunocytochemical studies reveal widespread pre- and postsynaptic, but sparse to undetectable somal, localization of this enzyme. Further, the superficial location of the avian HP makes possible the more exclusive manipulation of its neurochemical characteristics without perturbation of the neuropil and the resultant induction of astroglial aromatase. Last, as in other vertebrates, the HP is critical for spatial memory performance in this species. Here we report that local inhibition of hippocampal aromatization impairs spatial memory performance in an ecologically valid food-finding task. Local aromatase inhibition also resulted in lower levels of estradiol in the HP, but not in adjacent brain areas, and was achieved without the induction of astroglial aromatase. The observed decrement in acquisition and subsequent memory performance as a consequence of lowered aromatization was similar to that achieved by lesioning this locus. Thus, hippocampal aromatization, much of which is achieved at the synapse in this species, is critical for spatial memory performance.

scholarly journals Hippocampal-dependent learning requires a functional circadian system

2008 ◽  
Vol 105 (40) ◽  
pp. 15593-15598 ◽  
Author(s):  
Norman F. Ruby ◽  
Calvin E. Hwang ◽  
Colin Wessells ◽  
Fabian Fernandez ◽  
Pei Zhang ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Memory Performance ◽  
Memory Function ◽  
Recognition Task ◽  
Learning Task ◽  
Brain Regions ◽  
Circadian System ◽  
Surgical Ablation ◽  
Novel Object ◽  
Dependent Learning

Decades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN) and clock gene knockouts eliminate rhythms, but also damage adjacent brain regions or cause developmental effects that may impair cognitive or other physiological functions. We developed a method that avoids these problems and eliminates rhythms by noninvasive means in Siberian hamsters (Phodopus sungorus). The present study evaluated cognitive function in arrhythmic animals by using a hippocampal-dependent learning task. Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training. Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance. The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms. We conclude that the circadian system is involved in memory function in a manner that is independent of sleep. Circadian influence on learning may be exerted via cyclic GABA output from the SCN to target sites involved in learning. Arrhythmic hamsters may have failed to perform this task because of chronic inhibitory signaling from the SCN that interfered with the plastic mechanisms that encode learning in the hippocampus.

Nervous System Deletion of Mammalian INDY in Mice Mimics Dietary Restriction-Induced Memory Enhancement

2020 ◽  
Vol 76 (1) ◽  
pp. 50-56
Author(s):  
Shou-Zen Fan ◽  
Chih-Wei Sung ◽  
Yi-Hsuan Tsai ◽  
Sheng-Rong Yeh ◽  
Wei-Sheng Lin ◽  
...  
Keyword(s):  
Nervous System ◽  
Dietary Restriction ◽  
Motor Coordination ◽  
Granule Cells ◽  
Memory Performance ◽  
Memory Function ◽  
Critical Role ◽  
Hippocampal Neurogenesis ◽  
Physiological Status ◽  
Specific Deletion

Abstract Reduced expression of the Indy (I’m Not Dead Yet) gene extends life span in Caenorhabditis elegans and Drosophila melanogaster and improves the metabolic heath of Mus musculus through inducing a physiological status akin to dietary restriction (DR). Although the function of Indy in aging and hepatic metabolism has been extensively studied, its role in the mouse nervous system remains unclear. Here, we explore the effect of mammalian Indy (mIndy, SLC13A5) gene deletion on murine cognitive function. Similar to what is seen in DR animals, systemic deletion of the mIndy gene (mIndy knockout [KO]) significantly improves memory performance and motor coordination of mice. Both DR and mIndy KO mice act normally in other behavioral tasks, including emotional, social, and food-seeking behaviors. Moreover, we find that tissue-specific deletion of mIndy in the nervous system is sufficient to improve memory performance, while liver-specific deletion has no effect on memory, and results in tests of motor coordination show no changes in either mutant. Mice with systemic or nervous system deletion of mIndy also exhibit increased hippocampal neurogenesis and dendritic spine formation in dentate granule cells; these changes are well-documented contributors to enhanced memory performance. Together, our studies demonstrate a critical role for brain-derived mIndy expression in the regulation of memory function in animals.

scholarly journals A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction

2020 ◽  
Vol 26 (34) ◽  
pp. 4330-4337
Author(s):  
Jennifer Gile ◽  
Yoshimasa Oyama ◽  
Sydney Shuff ◽  
Tobias Eckle
Keyword(s):  
Cognitive Function ◽  
Mrna Expression ◽  
Cognitive Dysfunction ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Expression Levels ◽  
Inflammatory Phenotype ◽  
Dependent Learning ◽  
Mrna Expression Levels

Background: We recently reported a role for the circadian rhythm protein Period 2 (PER2) in midazolam induced cognitive dysfunction. Based on previous studies showing a critical role for the adenosine A2B receptor (ADORA2B) in PER2 regulation, we hypothesized that hippocampal ADORA2B is crucial for cognitive function. Methods: Midazolam treated C57BL/6J mice were analyzed for Adora2b hippocampal mRNA expression levels, and spontaneous T-maze alternation was determined in Adora2b-/- mice. Using the specific ADORA2B agonist BAY-60-6583 in midazolam treated C57BL/6J mice, we analyzed hippocampal Per2 mRNA expression levels and spontaneous T-maze alternation. Finally, Adora2b-/- mice were assessed for mRNA expression of markers for inflammation or cognitive function in the hippocampus. Results: Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced in Adora2b-/- mice. ADORA2B agonist BAY-60-6583 restored midazolam mediated reduction in spontaneous alternation in C57BL/6J mice. Analysis of hippocampal Tnf-α or Il-6 mRNA levels in Adora2b-/- mice did not reveal an inflammatory phenotype. However, C-fos, a critical component of hippocampus-dependent learning and memory, was significantly downregulated in the hippocampus of Adora2b-/- mice. Conclusion: These results suggest a role of ADORA2B in midazolam induced cognitive dysfunction. Further, our data demonstrate that BAY-60-6583 treatment restores midazolam induced cognitive dysfunction, possibly via increases of Per2. Additional mechanistic studies hint towards C-FOS as another potential underlying mechanism of memory impairment in Adora2b-/- mice. These findings suggest the ADORA2B agonist as a potential therapy in patients with midazolam induced cognitive dysfunction.

Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽  
2014 ◽  
Vol 27 (4) ◽  
pp. 161-169 ◽  
Author(s):  
Nienke A. Hofrichter ◽  
Sandra Dick ◽  
Thomas G. Riemer ◽  
Carsten Schleussner ◽  
Monique Goerke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serial Position ◽  
Episodic Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Word List ◽  
Position Effects ◽  
Serial Position Effects ◽  
List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

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