Changes In Spatial Working Memory Research Articles

Maternal hypertension alters offspring’s glial cell proportions and behavior

Abstract Preeclampsia (PreE), a hypertensive disorder during pregnancy, is a primary contributor to global obstetric morbidity and mortality. Its effects encompass heightened risks of cognitive impairment and behavior disorders in children born to mothers with PreE. The objective of our study was to determine whether PreE leads to early modifications in the brain's glial cell populations and/or behavioral changes in offspring. To induce PreE, C57BL/6J dams received vasopressin or saline through subcutaneous infusion throughout gestation. Following natural parturition, offspring were euthanized at various postnatal timepoints for glial cell analysis and behavioral evaluation. Flow cytometry was utilized to assess microglia and astrocyte populations. Offspring of PreE pregnancies exhibited decreased total microglia and astrocytes in the brain. Additionally, when compared to offspring from normotensive pregnancies, those born to mothers with PreE displayed impaired performance in the spontaneous alternation Plus-maze task, signifying altered spatial working memory. Our findings substantiate that PreE leads to diminished glial cell populations in offspring postnatally, and these mice exhibit changes in spatial working memory. Continuing research aims to elucidate the influence of PreE on the numbers and functioning of glial cells, along with examining how the compromised numbers and/or functionality of these cells affects the behavior and cognition of offspring born to mothers with PreE.

Gadolinium Retention in the Central and Peripheral Nervous System: Implications for Pain, Cognition, and Neurogenesis.

Background Despite the wide use of gadolinium-based contrast agents (GBCAs) for enhanced MRI, their neurochemical and behavioral consequences, if any, remain poorly understood. Purpose To investigate the effect of repeated exposure to a linear or macrocyclic GBCA on gadolinium retention in the central and peripheral nervous system of rats and to assess the functional implications of such retention on hippocampal neurogenesis and sensory and cognitive processing. Materials and Methods Seventy male Sprague-Dawley rats (4 weeks old) received intraperitoneal injections of gadoterate meglumine (0.6 or 2.5 mmol per kilogram of body weight), gadodiamide (0.6 or 2.5 mmol/kg), or saline daily for 20 days (February 2018-March 2019). The 5-bromo-2'-deoxyuridine injections were administered every 3 days to determine the number of proliferating cells and the number of newly maturing neurons in the hippocampus. Sensory and cognitive behavioral tests were performed to assess the effect of GBCAs on pain sensitivity and spatial working memory function, respectively. Finally, inductively coupled plasma mass spectrometry analysis was used to quantify gadolinium retention in the brain, spinal cord, and peripheral nerves 24 hours after the last GBCA administration. One-way and mixed-design analyses of variance were used for statistical analysis. Results All GBCAs resulted in significant gadolinium retention in central and peripheral nervous tissues (1.8-333.2 nmol Gd/g tissue). Pain hypersensitivity to thermal and mechanical stimuli (P < .001) was observed after gadodiamide exposure in rats but not after gadoterate meglumine exposure. Rats injected with both GBCAs showed no changes in spatial working memory or in hippocampal cell proliferation and maturation. Conclusion Gadolinium was retained in the spinal cord and peripheral nerves in rats exposed to multiple administrations of linear and macrocyclic contrast agents. Gadodiamide (linear contrast agent) but not gadoterate meglumine (macrocyclic contrast agent) led to pain hypersensitivity, but neither affected spatial working memory performance, hippocampal cellular proliferation, or hippocampal neurogenesis. © RSNA, 2020 See also the editorial by Radbruch in this issue.

Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment.

Closely linked to Alzheimer’s disease (AD), the pathological spectrum of vascular cognitive impairment (VCI) is known to be wide and complex. Considering that multiple instead of a single targeting approach is considered a treatment option for such complicated diseases, the multifaceted aspects of mesenchymal stem cells (MSCs) make them a suitable candidate to tackle the heterogeneity of VCI. MSCs were delivered via the intracerebroventricular (ICV) route in mice that were subjected to VCI by carotid artery stenosis. VCI was induced in C57BL6/J mice wild type (C57VCI) mice by applying a combination of ameroid constrictors and microcoils, while ameroid constrictors alone were bilaterally applied to 5xFAD (transgenic AD mouse model) mice (5xVCI). Compared to the controls (minimal essential medium (MEM)-injected C57VCI mice), changes in spatial working memory were not noted in the MSC-injected C57VCI mice, and unexpectedly, the mortality rate was higher. In contrast, compared to the MEM-injected 5xVCI mice, mortality was not observed, and the spatial working memory was also improved in MSC-injected 5xVCI mice. Disease progression of the VCI-induced mice seems to be affected by the method of carotid artery stenosis and due to this heterogeneity, various factors must be considered to maximize the therapeutic benefits exerted by MSCs. Factors, such as the optimal MSC injection time point, cell concentration, sacrifice time point, and immunogenicity of the transplanted cells, must all be adequately addressed so that MSCs can be appropriately and effectively used as a treatment option for VCI.

The effect of caloric restriction on working memory in healthy non-obese adults.

We aim to evaluate the effect of caloric restriction (CR) in cognition by comparing performance in neuropsychological tests for working memory between a group of non-obese healthy subjects doing CR for 2 years with another consuming ad libitum diet (AL). This study was part of a larger multicenter trial called CALERIE that consisted of a randomized clinical trial with parallel-group comparing 2 years of 25% CR and AL in 220 volunteers with a BMI between 22 and 28 kg/m2, across 3 sites. The cognitive tests used were the Cambridge Neuropsychological Tests Automated Battery (CANTAB) for Spatial Working Memory (SWM) including the total number of errors (SWMTE) and strategy (SWMS). Included as possible moderators were sleep quality, mood states, perceived stress, and energy expenditure. Analyses were performed at baseline and months 12 and 24. After adjustments, there was a significantly greater improvement in working memory assessed by the SWM for CR individuals, compared to AL. At month 24, it was related mostly to lower protein intake, compared to other macronutrients. Changes in SWM were moderated by changes in sleep quality, physical activity, and energy expenditure. On the long term, CR in healthy individuals seems to have a slightly positive effect on working memory. The study of brain CR targets opens new possibilities to prevent and treat cognitive deficits.

A one-year classroom-randomized trial of mental abacus instruction for first- and second-grade students

Mental Abacus (MA) is a popular arithmetic technique in which students learn to solve math problems by visualizing a physical abacus structure. Prior studies conducted in Asia have found that MA can lead to exceptional mathematics achievement in highly motivated individuals, and that extensive training over multiple years can also benefit students in standard classroom settings. Here we explored the benefits of shorter-term MA training to typical students in a US school. Specifically, we tested whether MA (1) improves arithmetic performance relative to a standard math curriculum, and (2) leads to changes in spatial working memory, as claimed by several recent reports. To address these questions, we conducted a one-year, classroom-randomized trial of MA instruction. We found that first-graders students struggled to achieve abacus expertise over the course of the year, while second-graders were more successful. Neither age group showed a significant advantage in cognitive abilities or mathematical computation relative to controls, although older children showed some hints of an advantage in learning place-value concepts. Overall, our results suggest caution in the adoption of MA as a short-term educational intervention.

Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophrenia.

Type-3 metabotropic glutamate receptor gene (GRM3) single nucleotide polymorphisms (SNPs) have been associated with cognitive performance and prefrontal cortex brain activity in chronically treated schizophrenia patients. Whether these SNPs are associated with cognitive and symptom response to antipsychotic therapy has not been extensively evaluated. The aim of the study was to examine pharmacogenetic relationships between GRM3 and selected variants in relevant dopamine genes with changes in spatial working memory and clinical symptoms after treatment. Sixty-one untreated first-episode schizophrenia patients were assessed before and after 6 weeks of antipsychotic pharmacotherapy, primarily consisting of risperidone. Patients' level of cognitive performance on a spatial working memory task was assessed with a translational oculomotor paradigm. Changes after treatment in cognitive and clinical measures were examined in relationship to genetic polymorphisms in the GRM3, COMT, and DRD2/ANKK1 gene regions. Spatial working memory performance worsened after antipsychotic treatment. This worsening was associated with GRM3 rs1468412, with the genetic subgroup of patients known to have altered glutamate activity having greater adverse changes in working memory performance after antipsychotic treatment. Negative symptom improvement was associated with GRM3 rs6465084. There were no pharmacogenetic associations between DRD2/ANKK1 and COMT with working memory changes or symptom response to treatment. These findings suggest important pharmacogenetic relationships between GRM3 variants and changes in cognition and symptom response with exposure to antipsychotics. This information may be useful in identifying patients susceptible to adverse cognitive outcomes associated with antipsychotic treatment and suggest that glutamatergic mechanisms contribute to such effects.

The Anabolic Androgenic Steroid Testosterone Propionate Decreases Recognition Memory in Adult Male Rats

Although there are therapeutic applications of the Anabolic Androgenic Steroids (AAS), the predominant use implies the illicit self-administration by athletes and adolescents. In this respect, AAS abuse is associated with untoward effects on brain and behavior. Exposure to supraphysiological doses of AAS leads to changes in anxiety and aggression, but their effects on cognitive functions are poorly understood. We investigated the effects of the AAS testosterone propionate (TP), acutely or chronically administered in supraphysiological doses, on memory in rats. Experiment I - Adult male Wistar rats were treated once with vehicle (Control group, n = 5) or TP (10 mg/kg, n = 5). Behavioral experiments were performed 60 minutes after the single injection, and included the evaluation of spatial working memory and recognition memory. Experiment II - The rats received repeated daily administration of vehicle (n = 6) or TP (n = 7) for 40 days. Behavioral experiments started 23 hours after the last injection. After behavioral procedures, the animals were euthanized, the blood was collected for biochemical analyses and testicles were removed and weighted. Regarding the behavioral assessment, rats chronically treated with TP presented decreased time exploring the novel object when compared to control group. Rats that were treated acutely showed no significant difference compared with control. Acute or chronic treatments with TP were not effective in promoting changes in spatial working memory. Additionally, chronic treatment with TP induced significantly increases in biochemistry marker the enzyme glutamate pyruvate transaminase (SGPT) and a reduction in testicular weight as compared with control. Even though not interfering with spatial working memory performance, AAS abuse could induce deficit on recognition memory.

Phenolic Acid Intake, DeliveredViaModerate Champagne Wine Consumption, Improves Spatial Working MemoryViathe Modulation of Hippocampal and Cortical Protein Expression/Activation

While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex.

The Influence of Prism Adaptation on Perceptual and Motor Components of Neglect: A Reply to Saevarsson and Kristjansson

The Influence of Prism Adaptation on Perceptual and Motor Components of Neglect: A Reply to Saevarsson and Kristjansson

Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway.

The effects of acute tyrosine and phenylalanine depletion on spatial working memory and planning in healthy volunteers are predicted by changes in striatal dopamine levels

Dopamine (DA) is considered important in the modulation of tasks of spatial working memory. However, the findings from studies in humans to date are mixed. While this may be due to the characteristics of the tasks used, it is also possible that these findings are explained by variable central effects of the manipulations used. To test the effects of acute tyrosine and phenylalanine depletion (TPD, which reduces synthesis and release of brain DA) on cognitive function and relate changes in performance accuracy to the central effects of TPD measured with [11C]raclopride positron emission tomography (PET). Fourteen participants were given tests of spatial working memory, planning, verbal memory span and trial-and-error learning after acute TPD, seven of whom also received PET scans to measure changes in striatal DA levels. Although TPD produced a clear reduction in tyrosine and phenylalanine availability to the brain, no impairments on any of the cognitive tests were observed. However, changes in spatial working memory and planning accuracy after TPD showed a highly significant relationship with the changes in striatal DA levels. Our findings suggest that the effects of TPD on spatial working memory and planning may be unreliable due to the variability of the changes in brain DA levels achieved with this manipulation.

Different time course for age-related changes of behavior in a complex spatial cone-field discrimination task in Lewis rats

Clear age-related impairments in learning and memory performance have consistently been reported for rodents in spatial discrimination tasks. The aim in the present study was to evaluate whether Lewis rats display age-associated changes in spatial working memory (WM) and reference memory (RM) performance and whether the changes in their performance on both memory components follow the same time course. Rats of five different ages of the Lewis strain were trained on a complex spatial discrimination task in a cone field. This task allows the simultaneous assessment of WM and RM. We observed that WM performance declined already between 4 and 12 months of age. RM performance, on the other hand, was better in the 18-, 24-, and 30-month-old animals than in the two youngest age groups. This was probably because the younger rats adopted the habit of extensively inspecting nonreinforced places. Correlation analysis of the data supported the view that WM and RM represent different aspects of spatial memory. The study corroborates the notion that distinct aspects of behavior decline differently with age.