scholarly journals Spatial Memory and Microglia Activation in a Mouse Model of Chronic Neuroinflammation and the Anti-inflammatory Effects of Apigenin

2021 ◽  
Vol 15 ◽  
Author(s):  
Rose Chesworth ◽  
Rashmi Gamage ◽  
Faheem Ullah ◽  
Sandra Sonego ◽  
Christopher Millington ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Healthy Aging ◽  
Memory Function ◽  
Microglia Activation ◽  
Memory Recall ◽  
Suitable Model ◽  
Barnes Maze ◽  
Wild Type ◽  
Chronic Neuroinflammation ◽  
Age Related

Chronic neuroinflammation characterized by microglia reactivity is one of the main underlying processes in the initiation and progression of neurodegenerative diseases such as Alzheimer’s disease. This project characterized spatial memory during healthy aging and prolonged neuroinflammation in the chronic neuroinflammatory model, glial fibrillary acidic protein-interleukin 6 (GFAP-IL6). We investigated whether chronic treatment with the natural flavonoid, apigenin, could reduce microglia activation in the hippocampus and improve spatial memory. GFAP-IL6 transgenic and wild-type-like mice were fed with apigenin-enriched or control chow from 4 months of age and tested for spatial memory function at 6 and 22 months using the Barnes maze. Brain tissue was collected at 22 months to assess microgliosis and morphology using immunohistochemistry, stereology, and 3D single cell reconstruction. GFAP-IL6 mice showed age-dependent loss of spatial memory recall compared with wild-type-like mice. Chronic apigenin treatment decreased the number of Iba-1+ microglia in the hippocampus of GFAP-IL6 mice and changed microglial morphology. Apigenin did not reverse spatial memory recall impairment in GFAP-IL6 mice at 22 months of age. GFAP-IL6 mice may represent a suitable model for age-related neurodegenerative disease. Chronic apigenin supplementation significantly reduced microglia activation, but this did not correspond with spatial memory improvement in the Barnes Maze.

scholarly journals Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice

2020 ◽  
Vol 117 (38) ◽  
pp. 23925-23931
Author(s):  
Karoline Degenhardt ◽  
Jessica Wagner ◽  
Angelos Skodras ◽  
Michael Candlish ◽  
Anna Julia Koppelmann ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Vascular Dysfunction ◽  
Upper Body ◽  
Dependent Manner ◽  
Wild Type ◽  
Brain Vasculature ◽  
Cerebrovascular Function ◽  
Age Related ◽  
Novel Approach ◽  
Cerebrovascular Dysfunction

Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging.

scholarly journals Deleterious Effects of Ethanol, Δ(9)-Tetrahydrocannabinol (THC), and Their Combination on the Spatial Memory and Cognitive Flexibility in Adolescent and Adult Male Rats in the Barnes Maze Task

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 654
Author(s):  
Ewa Gibula-Tarlowska ◽  
Karolina Wydra ◽  
Jolanta H. Kotlinska
Keyword(s):  
Spatial Memory ◽  
Cognitive Flexibility ◽  
Drugs Of Abuse ◽  
Memory Function ◽  
Male Rats ◽  
Spatial Learning And Memory ◽  
Barnes Maze ◽  
Maze Task ◽  
Adult Rats ◽  
Ethanol Abuse

Research demonstrates that adolescents differ from adults in their response to drugs of abuse. The aim of the present study was to examine the influence of ethanol, Δ9-tetrahydrocannabinol hydrochloride (THC), and a combination of these drugs given during adolescence on spatial memory in adolescent and adult rats. Thus, adolescent rats (postnatal day (PND) 30) were subjected to the following groups: 0.9% NaCl; 1.5 g/kg ethanol; 1.0 mg/kg THC; 1.5 g/kg ethanol + 1.0 mg/kg THC. Rats received drug injection four times at three-day intervals. One day after the last injection, half of the treated animals were tested in the Barnes maze task, whereas the remaining animals were tested on PND 70. Results show that there was a significant age effect on spatial memory in the Barnes maze task after these drug administrations. Adolescent animals demonstrated more potent deficits in the spatial learning and memory (probe trial) and in cognitive flexibility (reversal learning) than did adults. However, in adult rats that received these drugs in adolescence, memory decline was observed only after ethanol and ethanol + THC administration. Thus, our results are important in understanding the deleterious impact of THC and/or ethanol abuse during adolescence on memory function across the lifespan (adolescent versus adult).

scholarly journals Short-term block of CRH receptor in adults mitigates age-related memory impairments provoked by early-life adversity

2019 ◽  
Author(s):  
Annabel K. Short ◽  
Pamela M. Maras ◽  
Aidan L. Pham ◽  
Autumn S. Ivy ◽  
Tallie Z. Baram
Keyword(s):  
Spatial Memory ◽  
Early Life ◽  
Middle Age ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Sensitive Period ◽  
Early Life Adversity ◽  
Memory Impairments ◽  
Age Related

AbstractIn humans, early-life adversity (ELA) is associated with impairments in learning and memory that may emerge later in life. In rodent models, ELA directly impacts hippocampal neuron structure and connectivity with progressive deficits in long-term potentiation and spatial memory function. Previous work has demonstrated that augmented release and actions of the stress-activated neuropeptide, CRH, contribute to the deleterious effects of ELA on hippocampal structure and memory-function. Early-life adversity increases CRH production and levels, and blocking CRH receptor type 1 (CRHR1) within the hippocampus immediately following adversity prevented the memory and LTP problems caused by ELA. Here we queried if blocking CRHR1 during adulthood ameliorates the adverse impact of ELA on memory in middle age. Blocking CRHR1 for a week in two month old male rats prevented ELA-induced deficits in object recognition memory that emerge during middle age. The intervention failed to mitigate the reduction of spatial memory at 4 and 8 months, but restored hippocampus-dependent location memory in ELA-experiencing rats during middle age (12 months of age).Notably, neither ELA nor blocking CRHR1 influenced anxiety- or depression-related behaviors These findings suggest a sensitive period during which interventions can fully prevent long-lasting effects of ELA, yet indicate that interventions later in life offer significant benefits.

scholarly journals Enriching hippocampal memory function in older adults through video games

2019 ◽  
Author(s):  
Gregory D. Clemenson ◽  
Shauna M. Stark ◽  
Samantha M. Rutledge ◽  
Craig E.L. Stark
Keyword(s):  
Older Adults ◽  
Video Games ◽  
Cognitive Decline ◽  
Video Game ◽  
Environmental Enrichment ◽  
Healthy Aging ◽  
Memory Function ◽  
Living Environment ◽  
Age Related ◽  
Age Related Cognitive Decline

AbstractHealthy aging is accompanied by a steady cognitive decline with clear losses in memory. Animal studies have consistently demonstrated that simply modifying an animal’s living environment (known as environmental enrichment) can have a positive influence on age-related cognitive decline in the hippocampus. Previously, we showed that playing immersive 3D video games can improve hippocampal-based memory in young healthy adults, suggesting that the exploration of the large open worlds of modern-day video games may act as proxy for environmental enrichment in humans. Here, we replicated our previous video game study in older adults and showing that playing video games for 4 weeks can improve hippocampal-based memory in a population that is already experiencing age-related decline in this memory. Furthermore, we showed that the improvements last for up to 4 weeks past the intervention, highlighting the potential of video games as intervention for age-related cognitive decline.

scholarly journals Neuropathological approaches to cerebral aging and neuroplasticity

2013 ◽  
Vol 15 (1) ◽  
pp. 29-43 ◽  
Keyword(s):  
Adult Neurogenesis ◽  
Healthy Aging ◽  
Brain Plasticity ◽  
Hippocampal Formation ◽  
Memory Function ◽  
Elderly Subjects ◽  
Preclinical Alzheimer’S Disease ◽  
Age Related ◽  
The Brain ◽  
Age Related Changes

Cerebral aging is a complex and heterogenous process related to a large variety of molecular changes involving multiple neuronal networks, due to alterations of neurons (synapses, axons, dendrites, etc), particularly affecting strategically important regions, such as hippocampus and prefrontal areas. A substantial proportion of nondemented, cognitively unimpaired elderly subjects show at least mild to moderate, and rarely even severe, Alzheimer-related lesions, probably representing asymptomatic preclinical Alzheimer's disease, and/or mixed pathologies. While the substrate of resilience to cognitive decline in the presence of abundant pathologies has been unclear, recent research has strengthened the concept of cognitive or brain reserve, based on neuroplasticity or the ability of the brain to manage or counteract age-related changes or pathologies by reorganizing its structure, connections, and functions via complex molecular pathways and mechanisms that are becoming increasingly better understood. Part of neuroplasticity is adult neurogenesis in specific areas of the brain, in particular the hippocampal formation important for memory function, the decline of which is common even in "healthy" aging. To obtain further insights into the mechanisms of brain plasticity and adult neurogenesis, as the basis for prevention and potential therapeutic options, is a major challenge of modern neurosciences.

scholarly journals Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 610
Author(s):  
Jessica C. Gaspar ◽  
Catherine Healy ◽  
Mehnaz I. Ferdousi ◽  
Michelle Roche ◽  
David P. Finn
Keyword(s):  
Spatial Memory ◽  
Cognitive Processing ◽  
Inflammatory Pain ◽  
Dorsal Hippocampus ◽  
Memory Function ◽  
Intraperitoneal Administration ◽  
Compensatory Mechanism ◽  
Chronic Inflammatory Pain ◽  
Pharmacological Blockade ◽  
Innate Anxiety

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPARα, PPARβ/δ and PPARγ. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether endogenous signalling via PPARs differentially modulates innate anxiety responses and mnemonic function in the presence and absence of inflammatory pain. We examined the effects of intraperitoneal administration of GW6471 (PPARα antagonist), GSK0660 (PPARβ/δ antagonist), GW9662 (PPARγ antagonist), and N-palmitoylethanolamide (PEA) on rat behaviour in the elevated plus maze (EPM), open field (OF), light-dark box (LDB), and novel object recognition (NOR) tests in the presence or absence of chronic inflammatory pain. Complete Freund’s Adjuvant (CFA)-injected rats exhibited impaired recognition and spatial mnemonic performance in the NOR test and pharmacological blockade of PPARα further impaired spatial memory in CFA-treated rats. N-oleoylethanolamide (OEA) levels were higher in the dorsal hippocampus in CFA-injected animals compared to their counterparts. The results suggest a modulatory effect of CFA-induced chronic inflammatory pain on cognitive processing, but not on innate anxiety-related responses. Increased OEA-PPARα signalling may act as a compensatory mechanism to preserve spatial memory function following CFA injection.

scholarly journals Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot Kaur Grewal ◽  
Shruti Chandra ◽  
Alan Bird ◽  
Glen Jeffery ◽  
Sobha Sivaprasad
Keyword(s):  
Macular Degeneration ◽  
Healthy Aging ◽  
Intraclass Correlation ◽  
Age Related Macular Degeneration ◽  
Healthy Individuals ◽  
Age Related ◽  
Rod Function ◽  
The Mean ◽  
Highly Correlated ◽  
Effect Of Age

AbstractTo evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

scholarly journals Autobiographical Memory in Normal Ageing and Dementia

1991 ◽  
Vol 4 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Harvey J. Sagar ◽  
Edith V. Sullivan ◽  
Suzanne Corkin
Keyword(s):  
Memory Function ◽  
Early Adulthood ◽  
Normal Subjects ◽  
Elderly Subjects ◽  
Retrieval Cues ◽  
Age Related ◽  
Normal Ageing ◽  
Severity Of Dementia ◽  
And Control ◽  
Cue Words

Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD) in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

Neuroprotection and Enhancement of Spatial Memory by Herbal Mixture HT008-1 in Rat Global Brain Ischemia Model

2008 ◽  
Vol 36 (02) ◽  
pp. 287-299 ◽  
Author(s):  
Yun Tai Kim ◽  
Youn-Ju Yi ◽  
Mi-Yeon Kim ◽  
Youngmin Bu ◽  
Zhen Hua Jin ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Brain Ischemia ◽  
Neuronal Damage ◽  
Memory Function ◽  
Neuronal Cell ◽  
Memory Deficit ◽  
Global Brain Ischemia ◽  
Herbal Mixture ◽  
Y Maze ◽  
Global Brain

To investigate whether HT008-1, a prescription used in traditional Korean medicine to treat mental and physical weakness, has a neuroprotective effect on a rat model of global brain ischemia and an enhancing effect against memory deficit following ischemia. Global brain ischemia was induced for 10 min by using 4-vessel occlusion (4-VO). HT008-1 was orally administered at doses of 30, 100, and 300 mg/kg respectively twice at 0 and 90 min after ischemia. The effect on memory deficit was investigated by using a Y-maze neurobehavioral test 4 days after brain ischemia, and the effect on neuronal damage was measured 7 days after ischemia. The mechanism of action was studied immunohistochemically using an anti-CD11b (OX-42) antibody. The oral administration of HT008-1 at 100 and 300 mg/kg significantly reduced hippocampal neuronal cell death by 49% and 53%, respectively, compared with a vehicle-treated group, and also improved spatial memory function in the Y-maze test. Immunohistochemically, HT008-1 inhibited OX-42 expression in the hippocampus. The effects of HT008-1 were more pronounced than those of its individual herb components. The herbal mixture HT008-1 protects the most vulnerable CA1 pyramidal cells of the hippocampus and enhances spatial memory function against global brain ischemia; an anti-inflammatory effect may be one of the mechanisms of action.

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