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1.
Methods Mol Biol ; 2799: 107-138, 2024.
Article En | MEDLINE | ID: mdl-38727905

NMDAR-dependent forms of synaptic plasticity in brain regions like the hippocampus are widely believed to provide the neural substrate for long-term associative memory formation. However, the experimental data are equivocal at best and may suggest a more nuanced role for NMDARs and synaptic plasticity in memory. Much of the experimental data available comes from studies in genetically modified mice in which NMDAR subunits have been deleted or mutated in order to disrupt NMDAR function. Behavioral assessment of long-term memory in these mice has involved tests like the Morris watermaze and the radial arm maze. Here we describe these behavioral tests and some of the different testing protocols that can be used to assess memory performance. We discuss the importance of distinguishing selective effects on learning and memory processes from nonspecific effects on sensorimotor or motivational aspects of performance.


Maze Learning , Memory, Long-Term , Receptors, N-Methyl-D-Aspartate , Spatial Memory , Animals , Receptors, N-Methyl-D-Aspartate/metabolism , Mice , Memory, Long-Term/physiology , Maze Learning/physiology , Spatial Memory/physiology , Hippocampus/physiology , Hippocampus/metabolism , Behavior, Animal/physiology , Neuronal Plasticity/physiology
2.
PLoS One ; 19(5): e0298116, 2024.
Article En | MEDLINE | ID: mdl-38722850

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as mental rotation and visuospatial working memory, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in various disorders (e.g., Alzheimer's disease) where spatial impairment is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest (SHQ), as a measure of navigation ability in a sample of young, predominantly female university students (N = 78; 20; female = 74.3%; mean age = 20.33 years). We used three separate tests of navigation embedded in SHQ: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will also be good at path integration, have a superior memory in a radial arm maze, or rate themself as having a strong sense of direction. However, we observed that participants who were good in the wayfinding task of SHQ tended to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the associations between different abilities involved in spatial navigation.


Spatial Navigation , Humans , Female , Spatial Navigation/physiology , Male , Young Adult , Adult , Memory, Short-Term/physiology , Spatial Memory/physiology , Maze Learning/physiology , Space Perception/physiology , Adolescent , Mobile Applications
3.
PLoS One ; 19(5): e0302989, 2024.
Article En | MEDLINE | ID: mdl-38753604

Multiple sensorimotor loops converge in the motor cortex to create an adaptable system capable of context-specific sensorimotor control. Afferent inhibition provides a non-invasive tool to investigate the substrates by which procedural and cognitive control processes interact to shape motor corticospinal projections. Varying the transcranial magnetic stimulation properties during afferent inhibition can probe specific sensorimotor circuits that contribute to short- and long-latency periods of inhibition in response to the peripheral stimulation. The current study used short- (SAI) and long-latency (LAI) afferent inhibition to probe the influence of verbal and spatial working memory load on the specific sensorimotor circuits recruited by posterior-anterior (PA) and anterior-posterior (AP) TMS-induced current. Participants completed two sessions where SAI and LAI were assessed during the short-term maintenance of two- or six-item sets of letters (verbal) or stimulus locations (spatial). The only difference between the sessions was the direction of the induced current. PA SAI decreased as the verbal working memory load increased. In contrast, AP SAI was not modulated by verbal working memory load. Visuospatial working memory load did not affect PA or AP SAI. Neither PA LAI nor AP LAI were sensitive to verbal or spatial working memory load. The dissociation of short-latency PA and AP sensorimotor circuits and short- and long-latency PA sensorimotor circuits with increasing verbal working memory load support multiple convergent sensorimotor loops that provide distinct functional information to facilitate context-specific supraspinal control.


Memory, Short-Term , Motor Cortex , Transcranial Magnetic Stimulation , Humans , Memory, Short-Term/physiology , Motor Cortex/physiology , Male , Female , Adult , Young Adult , Spatial Memory/physiology , Reaction Time/physiology , Evoked Potentials, Motor/physiology
4.
PLoS One ; 19(5): e0302850, 2024.
Article En | MEDLINE | ID: mdl-38748711

BACKGROUND AND AIM: Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats. EXPERIMENTAL PROCEDURE: The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level. RESULT: Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group. CONCLUSIONS: Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms.


Dementia, Vascular , Disease Models, Animal , Hippocampus , Long-Term Potentiation , Lutein , Neuronal Plasticity , Animals , Dementia, Vascular/drug therapy , Dementia, Vascular/physiopathology , Rats , Male , Neuronal Plasticity/drug effects , Long-Term Potentiation/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Lutein/pharmacology , Lutein/administration & dosage , Lutein/therapeutic use , Memory/drug effects , Rats, Wistar , Spatial Memory/drug effects , Dose-Response Relationship, Drug , Maze Learning/drug effects , Synaptic Transmission/drug effects
5.
Behav Brain Res ; 468: 115039, 2024 Jun 25.
Article En | MEDLINE | ID: mdl-38718877

Chronic unpredictable mild stress (CUMS) method has been introduced as a rodent model of depression. On the other hand, olanzapine, as an antipsychotic, can induce antidepressant and antipsychotic effects. Also, olanzapine may improve cognitive functions. Both CUMS and olanzapine can also affect the expression level of brain-derived neurotrophic factor (BDNF) and synaptophysin, the molecular factors involved in synaptic function, and learning and memory. In this study, we investigated the effect of olanzapine on locomotor activity (using open field test), pain threshold (using hot plate), depressive-like behavior (using forced swim test), spatial learning and memory (using Morris water maze), and BDNF and synaptophysin hippocampal expression (using real-time PCR) in both male and female CUMS rats. CUMS was performed for three consecutive weeks. Olanzapine was also injected intraperitoneally at the dose of 5 mg/kg. Our data showed that olanzapine can reverse the effects of CUMS on behavioral functions and BDNF and synaptophysin expression levels in the hippocampus of both males and females. It was also shown that olanzapine effects on spatial memory, pain perception, and BDNF and synaptophysin level were stronger in females than males. In conclusion, we suggested that the therapeutic effects of olanzapine in CUMS rats may be closely related to the function of BDNF and synaptophysin. Also, the therapeutic effects of olanzapine may be stronger in females. Therefore, and for the first time, we showed that there may be a sex difference in the effects of olanzapine on behavioral and molecular changes following CUMS.


Brain-Derived Neurotrophic Factor , Depression , Disease Models, Animal , Hippocampus , Olanzapine , Pain Perception , Spatial Memory , Stress, Psychological , Synaptophysin , Animals , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/drug effects , Male , Synaptophysin/metabolism , Female , Olanzapine/pharmacology , Stress, Psychological/metabolism , Stress, Psychological/drug therapy , Rats , Depression/drug therapy , Depression/metabolism , Spatial Memory/drug effects , Hippocampus/metabolism , Hippocampus/drug effects , Pain Perception/drug effects , Pain Perception/physiology , Behavior, Animal/drug effects , Memory Disorders/drug therapy , Memory Disorders/metabolism , Antipsychotic Agents/pharmacology , Rats, Sprague-Dawley
7.
CNS Neurosci Ther ; 30(5): e14719, 2024 May.
Article En | MEDLINE | ID: mdl-38783536

BACKGROUND: Methamphetamine (METH) is a psychostimulant substance with highly addictive and neurotoxic effects, but no ideal treatment option exists to improve METH-induced neurocognitive deficits. Recently, mesenchymal stem cells (MSCs)-derived exosomes have raised many hopes for treating neurodegenerative sequela of brain disorders. This study aimed to determine the therapeutic potential of MSCs-derived exosomes on cognitive function and neurogenesis of METH-addicted rodents. METHODS: Male BALB/c mice were subjected to chronic METH addiction, followed by intravenous administration of bone marrow MSCs-derived exosomes. Then, the spatial memory and recognition memory of animals were assessed by the Barnes maze and the novel object recognition test (NORT). The neurogenesis-related factors, including NeuN and DCX, and the expression of Iba-1, a microglial activation marker, were assessed in the hippocampus by immunofluorescence staining. Also, the expression of inflammatory cytokines, including TNF-α and NF-κB, were evaluated by western blotting. RESULTS: The results showed that BMSCs-exosomes improved the time spent in the target quadrant and correct-to-wrong relative time in the Barnes maze. Also, NORT's discrimination index (DI) and recognition index (RI) were improved following exosome therapy. Additionally, exosome therapy significantly increased the expression of NeuN and DCX in the hippocampus while decreasing the expression of inflammatory cytokines, including TNF-α and NF-κB. Besides, BMSC-exosomes down-regulated the expression of Iba-1. CONCLUSION: Our findings indicate that BMSC-exosomes mitigated METH-caused cognitive dysfunction by improving neurogenesis and inhibiting neuroinflammation in the hippocampus.


Amphetamine-Related Disorders , Doublecortin Protein , Exosomes , Hippocampus , Mesenchymal Stem Cells , Methamphetamine , Mice, Inbred BALB C , Neurogenesis , Animals , Exosomes/metabolism , Male , Neurogenesis/drug effects , Neurogenesis/physiology , Mice , Methamphetamine/toxicity , Amphetamine-Related Disorders/therapy , Amphetamine-Related Disorders/psychology , Amphetamine-Related Disorders/metabolism , Hippocampus/metabolism , Hippocampus/drug effects , Cognition/drug effects , Cognition/physiology , Maze Learning/drug effects , Maze Learning/physiology , Recognition, Psychology/drug effects , Recognition, Psychology/physiology , Nerve Tissue Proteins/metabolism , Central Nervous System Stimulants/toxicity , Spatial Memory/drug effects , Spatial Memory/physiology , Microfilament Proteins/metabolism , Mesenchymal Stem Cell Transplantation/methods , Calcium-Binding Proteins , DNA-Binding Proteins
8.
eNeuro ; 11(5)2024 May.
Article En | MEDLINE | ID: mdl-38755011

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 min created a short-term memory (weak) that cannot be retrieved 1 d later, whereas 10 min exploration created a long-term memory (strong) that can be retrieved 1 d later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval 1 d later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 h. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of the novel object location. Additionally, hippocampal dopamine elevation during the retrieval of OLMs did not allow the recovery of weak memories and did not affect the retrieval of strong memory traces. Finally, dopamine elevation increased hippocampal theta oscillations, indicating that dopamine promotes the recurrent activation of specific groups of neurons. Our experiments demonstrate that hippocampal dopaminergic modulation during the encoding of OLMs depends on memory strength indicating that hyperdopaminergic levels that enhance weak experiences could compromise the normal storage of strong memories.


Dopamine , Hippocampus , Mice, Inbred C57BL , Spatial Memory , Animals , Dopamine/metabolism , Male , Spatial Memory/physiology , Hippocampus/physiology , Hippocampus/metabolism , Mice , Theta Rhythm/physiology , Exploratory Behavior/physiology , Mental Recall/physiology , Memory, Long-Term/physiology , Memory, Short-Term/physiology
9.
Physiol Behav ; 281: 114583, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38750806

The 5xFAD mouse model shows age-related weight loss as well as cognitive and motor deficits. Metabolic dysregulation, especially impaired insulin signaling, is also present in AD. This study examined whether intranasal delivery of insulin (INI) at low (0.875 U) or high (1.750 U) doses would ameliorate these deficits compared to saline in 10-month-old female 5xFAD and B6SJL wildtype (WT) mice. INI increased forelimb grip strength in the wire hang test in 5xFAD mice in a dose-dependent manner but did not improve the performance of 5xFAD mice on the balance beam. High INI doses reduced frailty scores in 5xFAD mice and improved spatial memory in both acquisition and reversal probe trials in the Morris water maze. INI increased swim speed in 5xFAD mice but had no effect on object recognition memory or working memory in the spontaneous alternation task, nor did it improve memory in the contextual or cued fear memory tasks. High doses of insulin increased the liver, spleen, and kidney weights and reduced brown adipose tissue weights. P-Akt signaling in the hippocampus was increased by insulin in a dose-dependent manner. Altogether, INI increased strength, reduced frailty scores, and improved visual spatial memory. Hypoglycemia was not present after INI, however alterations in tissue and organ weights were present. These results are novel and important as they indicate that intra-nasal insulin can reverse cognitive, motor and frailty deficits found in this mouse model of AD.


Administration, Intranasal , Disease Models, Animal , Frailty , Insulin , Mice, Transgenic , Muscle Strength , Spatial Memory , Animals , Insulin/administration & dosage , Insulin/pharmacology , Muscle Strength/drug effects , Spatial Memory/drug effects , Female , Frailty/drug therapy , Mice , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Alzheimer Disease/drug therapy , Maze Learning/drug effects , Dose-Response Relationship, Drug , Memory Disorders/drug therapy , Amyloid beta-Protein Precursor/genetics , Hand Strength/physiology , Fear/drug effects , Hippocampus/drug effects , Hippocampus/metabolism
10.
Cortex ; 175: 12-27, 2024 Jun.
Article En | MEDLINE | ID: mdl-38701643

Navigation through space is based on memory representations of landmarks ('place') or movement sequences ('response'). Over time, memory representations transform through consolidation. However, it is unclear how the transformation affects place and response navigation in humans. In the present study, healthy adults navigated to target locations in a virtual maze. The preference for using place and response strategies and the ability to recall place and response memories were tested after a delay of one hour (n = 31), one day (n = 30), or two weeks (n = 32). The different delays captured early-phase synaptic changes, changes after one night of sleep, and long-delay changes due to the reorganization of navigation networks. Our results show that the relative contributions of place and response navigation changed as a function of time. After a short delay of up to one day, participants preferentially used a place strategy and exhibited a high degree of visual landmark exploration. After a longer delay of two weeks, place strategy use decreased significantly. Participants now equally relied on place and response strategy use and increasingly repeated previously taken paths. Further analyses indicate that response strategy use predominantly occurred as a compensatory strategy in the absence of sufficient place memory. Over time, place memory faded before response memory. We suggest that the observed shift from place to response navigation is context-dependent since detailed landmark information, which strongly relied on hippocampal function, decayed faster than sequence information, which required less detail and depended on extra-hippocampal areas. We conclude that changes in place and response navigation likely reflect the reorganization of navigation networks during systems consolidation.


Memory Consolidation , Spatial Navigation , Humans , Male , Memory Consolidation/physiology , Spatial Navigation/physiology , Female , Adult , Young Adult , Space Perception/physiology , Spatial Memory/physiology , Hippocampus/physiology , Mental Recall/physiology , Maze Learning/physiology
11.
J Alzheimers Dis ; 99(3): 899-910, 2024.
Article En | MEDLINE | ID: mdl-38701150

Background: Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. Objective: We aimed to assess navigation cues for innovative spatial training in aging. Methods: Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Results: Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. Conclusions: These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded.


Cognitive Dysfunction , Mental Recall , Spatial Navigation , Virtual Reality , Humans , Cognitive Dysfunction/psychology , Male , Female , Aged , Spatial Navigation/physiology , Mental Recall/physiology , Cues , Spatial Memory/physiology , Neuropsychological Tests , Middle Aged , Aged, 80 and over
12.
Toxicol Appl Pharmacol ; 487: 116953, 2024 Jun.
Article En | MEDLINE | ID: mdl-38705400

INTRODUCTION: Research has unveiled the neurotoxicity of Bisphenol A (BPA) linked to neuropathological traits of Alzheimer's disease (AD) through varied mechanisms. This study aims to investigate the neuroprotective properties of cyanidin, an anthocyanin, in an in vivo model of BPA-induced Alzheimer's-like neuropathology. METHODS: Three-week-old Sprague-Dawley rats were randomly assigned to four groups: vehicle control, negative control (BPA exposure), low-dose cyanidin treatment (BPA + cyanidin 5 mg/kg), and high-dose cyanidin treatment (BPA + cyanidin 10 mg/kg). Spatial memory was assessed through behavioral tests, including the Y-maze, novel object recognition, and Morris water maze. After behavioral tests, animals were euthanized, and brain regions were examined for acetylcholinesterase inhibition, p-tau, Wnt3, GSK3ß, and ß-catenin levels, antioxidant activities, and histopathological changes. RESULTS: BPA-exposed groups displayed memory impairments, while cyanidin-treated groups showed significant memory improvement (p < 0.0001). Cyanidin down regulated p-tau and glycogen synthase kinase-3ß (GSK3ß) and restored Wnt3 and ß-catenin levels (p < 0.0001). Moreover, cyanidin exhibited antioxidant properties, elevating catalase and superoxide dismutase levels. The intervention significantly reduced the concentrations of acetylcholinesterase in the cortex and hippocampus in comparison to the groups treated with BPA (p < 0.0001). Significant gender-based disparities were not observed. CONCLUSION: Cyanidin demonstrated potent neuroprotection against BPA-induced Alzheimer's-like neuropathology by enhancing antioxidant defenses, modulating tau phosphorylation by restoring the Wnt/ß-catenin pathway, and ameliorating spatial memory deficits. This study highlights the therapeutic potential of cyanidin in countering neurotoxicity linked to BPA exposure.


Alzheimer Disease , Anthocyanins , Benzhydryl Compounds , Cognition , Neuroprotective Agents , Phenols , Rats, Sprague-Dawley , Spatial Memory , Wnt Signaling Pathway , Animals , Phenols/pharmacology , Phenols/toxicity , Benzhydryl Compounds/toxicity , Benzhydryl Compounds/pharmacology , Anthocyanins/pharmacology , Anthocyanins/therapeutic use , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Spatial Memory/drug effects , Male , Rats , Wnt Signaling Pathway/drug effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Cognition/drug effects , Disease Models, Animal , Maze Learning/drug effects , Brain/drug effects , Brain/metabolism , Brain/pathology
13.
Nature ; 629(8012): 630-638, 2024 May.
Article En | MEDLINE | ID: mdl-38720085

Hippocampal representations that underlie spatial memory undergo continuous refinement following formation1. Here, to track the spatial tuning of neurons dynamically during offline states, we used a new Bayesian learning approach based on the spike-triggered average decoded position in ensemble recordings from freely moving rats. Measuring these tunings, we found spatial representations within hippocampal sharp-wave ripples that were stable for hours during sleep and were strongly aligned with place fields initially observed during maze exploration. These representations were explained by a combination of factors that included preconfigured structure before maze exposure and representations that emerged during θ-oscillations and awake sharp-wave ripples while on the maze, revealing the contribution of these events in forming ensembles. Strikingly, the ripple representations during sleep predicted the future place fields of neurons during re-exposure to the maze, even when those fields deviated from previous place preferences. By contrast, we observed tunings with poor alignment to maze place fields during sleep and rest before maze exposure and in the later stages of sleep. In sum, the new decoding approach allowed us to infer and characterize the stability and retuning of place fields during offline periods, revealing the rapid emergence of representations following new exploration and the role of sleep in the representational dynamics of the hippocampus.


Hippocampus , Sleep , Spatial Memory , Animals , Rats , Action Potentials/physiology , Bayes Theorem , Hippocampus/cytology , Hippocampus/physiology , Maze Learning/physiology , Models, Neurological , Neurons/physiology , Sleep/physiology , Spatial Memory/physiology , Theta Rhythm/physiology , Wakefulness/physiology
14.
Neuroimage ; 293: 120632, 2024 Jun.
Article En | MEDLINE | ID: mdl-38701994

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20-70 years) and 15 healthy participants (closed form, 7 females, age range 26-56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.


Aging , Glutathione , Humans , Female , Middle Aged , Male , Adult , Aged , Glutathione/metabolism , Aging/metabolism , Aging/physiology , Young Adult , Spatial Memory/physiology , Occipital Lobe/metabolism , Gyrus Cinguli/metabolism , Brain/metabolism
15.
PLoS One ; 19(4): e0297995, 2024.
Article En | MEDLINE | ID: mdl-38564573

Visuo-spatial working memory (VSWM) for sequences is thought to be crucial for daily behaviors. Decades of research indicate that oscillations in the gamma and theta bands play important functional roles in the support of visuo-spatial working memory, but the vast majority of that research emphasizes measures of neural activity during memory retention. The primary aims of the present study were (1) to determine whether oscillatory dynamics in the Theta and Gamma ranges would reflect item-level sequence encoding during a computerized spatial span task, (2) to determine whether item-level sequence recall is also related to these neural oscillations, and (3) to determine the nature of potential changes to these processes in healthy cognitive aging. Results indicate that VSWM sequence encoding is related to later (∼700 ms) gamma band oscillatory dynamics and may be preserved in healthy older adults; high gamma power over midline frontal and posterior sites increased monotonically as items were added to the spatial sequence in both age groups. Item-level oscillatory dynamics during the recall of VSWM sequences were related only to theta-gamma phase amplitude coupling (PAC), which increased monotonically with serial position in both age groups. Results suggest that, despite a general decrease in frontal theta power during VSWM sequence recall in older adults, gamma band dynamics during encoding and theta-gamma PAC during retrieval play unique roles in VSWM and that the processes they reflect may be spared in healthy aging.


Memory, Short-Term , Mental Recall , Spatial Memory , Theta Rhythm , Electroencephalography
16.
Behav Neurosci ; 138(2): 125-141, 2024 Apr.
Article En | MEDLINE | ID: mdl-38661671

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


LDL-Receptor Related Proteins , Mice, Knockout , Selenium , Spatial Learning , Animals , Mice , Diet , Hippocampus/metabolism , LDL-Receptor Related Proteins/genetics , LDL-Receptor Related Proteins/metabolism , Maze Learning/physiology , Maze Learning/drug effects , Memory/physiology , Memory/drug effects , Selenium/administration & dosage , Selenium/deficiency , Selenium/pharmacology , Selenoprotein P/genetics , Selenoprotein P/metabolism , Spatial Learning/physiology , Spatial Learning/drug effects , Spatial Memory/physiology , Spatial Memory/drug effects
17.
Behav Brain Res ; 466: 114978, 2024 May 28.
Article En | MEDLINE | ID: mdl-38582410

PURPOSE: As the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions. METHODS: Metformin was administered orally to male Wistar rats (20-22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis. RESULTS: Impaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity. CONCLUSION: Our results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect.


Acetylcholine , Aging , Choline O-Acetyltransferase , Disease Models, Animal , Hippocampus , Memory Disorders , Metformin , Rats, Wistar , Scopolamine , Animals , Metformin/pharmacology , Metformin/administration & dosage , Scopolamine/pharmacology , Male , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Rats , Choline O-Acetyltransferase/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Aging/drug effects , Acetylcholine/metabolism , Acetylcholinesterase/metabolism , Maze Learning/drug effects , Hypoglycemic Agents/pharmacology , Spatial Memory/drug effects
18.
J Alzheimers Dis ; 99(1): 121-143, 2024.
Article En | MEDLINE | ID: mdl-38640149

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.


Alzheimer Disease , Disease Models, Animal , Memory Disorders , Rats, Wistar , Vanadium Compounds , Animals , Alzheimer Disease/pathology , Alzheimer Disease/chemically induced , Male , Vanadium Compounds/pharmacology , Rats , Memory Disorders/pathology , Memory Disorders/chemically induced , Maze Learning/drug effects , Brain/pathology , Brain/drug effects , Brain/metabolism , Spatial Memory/drug effects , Neurofibrillary Tangles/pathology , Neurofibrillary Tangles/drug effects , Plaque, Amyloid/pathology , Dendritic Spines/drug effects , Dendritic Spines/pathology , Administration, Inhalation
19.
Anim Cogn ; 27(1): 37, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38684551

For most primates living in tropical forests, food resources occur in patchworks of different habitats that vary seasonally in quality and quantity. Efficient navigation (i.e., spatial memory-based orientation) towards profitable food patches should enhance their foraging success. The mechanisms underpinning primate navigating ability remain nonetheless mostly unknown. Using GPS long-term tracking (596 days) of one group of wild western lowland gorillas (Gorilla gorilla gorilla), we investigated their ability to navigate at long distances, and tested for how the sun was used to navigate at any scale by improving landmark visibility and/or by acting as a compass. Long episodic movements ending at a distant swamp, a unique place in the home range where gorillas could find mineral-rich aquatic plants, were straighter and faster than their everyday foraging movements relying on spatial memory. This suggests intentional targeting of the swamp based on long-distance navigation skills, which can thus be efficient over a couple of kilometres. Interestingly, for both long-distance movements towards the swamp and everyday foraging movements, gorillas moved straighter under sunlight conditions even under a dense vegetation cover. By contrast, movement straightness was not markedly different when the sun elevation was low (the sun azimuth then being potentially usable as a compass) or high (so providing no directional information) and the sky was clear or overcast. This suggests that gorillas navigate their home range by relying on visual place recognition but do not use the sun azimuth as a compass. Like humans, who rely heavily on vision to navigate, gorillas should benefit from better lighting to help them identify landmarks as they move through shady forests. This study uncovers a neglected aspect of primate navigation. Spatial memory and vision might have played an important role in the evolutionary success of diurnal primate lineages.


Gorilla gorilla , Animals , Gorilla gorilla/physiology , Male , Female , Spatial Navigation , Sunlight , Spatial Memory , Movement , Homing Behavior
20.
Neurología (Barc., Ed. impr.) ; 39(3): 244-253, Abr. 2024. ilus, tab, graf
Article Es | IBECS | ID: ibc-231690

Introducción: La relación entre la corteza entorrinal y el hipocampo ha sido estudiada por diferentes autores, que han destacado la importancia de las células de cuadrícula, las células de posicionamiento y la conexión trisináptica en los procesos que regulan: la persistencia de la memoria espacial, explícita y reciente, y su posible afección con el envejecimiento. Objetivo: Observar si existen diferencias en el tamaño y número de células de cuadrícula contenidas en la lámina iii de la corteza entorrinal y en la capa granular del giro dentado del hipocampo de pacientes mayores. Métodos: Realizamos estudios posmortem del cerebro de 6 sujetos de edades comprendidas entre los 56 y 87 años. Los cortes de cerebros que contenían el giro dentado del hipocampo y la corteza entorrinal adyacente se tiñeron con el método de Klüver-Barrera, después se midió, mediante el programa Image J, el área neuronal individual, el área neuronal total, así como el número de neuronas, contenidas en cuadrículas rectangulares a nivel de la lámina iii de la corteza entorrinal y la lámina ii del giro dentado y se llevó a cabo un análisis estadístico. Resultados: Se ha observado una reducción de la población celular de la capa piramidal externa de la corteza entorrinal, así como de las neuronas de la capa granular del giro dentado relacionada con el envejecimiento. Conclusión: Nuestros resultados indican que el envejecimiento produce una disminución en el tamaño y la densidad neuronal en las células de cuadrícula de la corteza entorrinal y de posicionamiento del giro dentado.(AU)


Introduction: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. Objective: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. Methods: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. Results: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. Conclusion: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.(AU)


Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Entorhinal Cortex , Hippocampus , Spatial Memory , Neurology , Nervous System Diseases
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