scholarly journals Microglial Activation in the Right Amygdala-Entorhinal-Hippocampal Complex is Associated with Preserved Spatial Learning in App mice

NeuroImage ◽  
2020 ◽  
pp. 117707
Author(s):  
Gloria Biechele ◽  
Karin Wind ◽  
Tanja Blume ◽  
Christian Sacher ◽  
Leonie Beyer ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Microglial Activation ◽  
The Right ◽  
Hippocampal Complex

scholarly journals Pre-therapeutic Microglia Activation and Sex Determine Therapy Effects of Chronic Immunomodulation

2021 ◽  
Author(s):  
Gloria Biechele ◽  
Tanja Blume ◽  
Maximilian Deussing ◽  
Benedikt Zott ◽  
Yuan Shi ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Learning Performance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Activated Microglia ◽  
Ppar Γ ◽  
Amyloid Accumulation ◽  
Β Amyloid

Modulation of the innate immune system is emerging as a promising therapeutic strategy against Alzheimer's disease (AD). However, determinants of a beneficial therapeutic effect are ill-understood. Thus, we investigated the potential of 18 kDa translocator protein positron-emission-tomography (TSPO-PET) for assessment of microglial activation in mouse brain before and during chronic immunomodulation. Serial TSPO-PET was performed during five months of chronic microglia modulation by stimulation of peroxisome proliferator-activated receptor (PPAR)-γ with pioglitazone in two different mouse models of AD (PS2APP, AppNL-G-F). Using mixed statistical models on longitudinal TSPO-PET data, we tested for effects of therapy and sex on treatment response. We tested correlations of baseline with longitudinal measures of TSPO-PET, and correlations between PET results with spatial learning performance and β-amyloid accumulation of individual mice. Immunohistochemistry was used to determine the molecular source of the TSPO-PET signal. Pioglitazone-treated female PS2APP and AppNL-G-F mice showed attenuation of the longitudinal increases in TSPO-PET signal when compared to vehicle controls, whereas treated male AppNL-G-F mice showed the opposite effect. Baseline TSPO-PET strongly predicted changes in microglial activation in treated mice (R=-0.874, p<0.0001) but not in vehicle controls (R=-0.356, p=0.081). Reduced TSPO-PET signal upon treatment was associated with better spatial learning and higher fibrillar β-amyloid accumulation. Immunohistochemistry confirmed activated microglia to be the source of the TSPO-PET signal (R=0.952, p<0.0001). TSPO-PET represents a sensitive biomarker for monitoring of immunomodulation and closely reflects activated microglia. Pre-therapeutic assessment of baseline microglial activation and sex are strong predictors of individual immunomodulation effects and could serve for responder stratification.

scholarly journals Right stellate ganglion block improves learning and memory dysfunction and hippocampal injury in rats with sleep deprivation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongsheng Dai ◽  
Biqiong Zheng ◽  
Zenggui Yu ◽  
Shizhu Lin ◽  
Yijie Tang ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Caspase 3 ◽  
Stellate Ganglion ◽  
Stellate Ganglion Block ◽  
Spatial Learning And Memory ◽  
Memory Dysfunction ◽  
Ganglion Block ◽  
The Right

Abstract Background Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats. Methods Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels. Results Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1β and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased. Conclusions The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation.

Finding the right motivation: Genotype-dependent differences in effective reinforcements for spatial learning

2012 ◽  
Vol 226 (2) ◽  
pp. 397-403 ◽  
Author(s):  
Jiun Youn ◽  
Bart A. Ellenbroek ◽  
Inti van Eck ◽  
Sandra Roubos ◽  
Matthijs Verhage ◽  
...  
Keyword(s):  
Spatial Learning ◽  
The Right

Microglial activation in schizophrenia: Is translocator 18 kDa protein (TSPO) the right marker?

2020 ◽  
Vol 215 ◽  
pp. 167-172 ◽  
Author(s):  
Marjolein A.M. Sneeboer ◽  
Thalia van der Doef ◽  
Manja Litjens ◽  
N.B.B. Psy ◽  
J. Melief ◽  
...  
Keyword(s):  
Microglial Activation ◽  
The Right

scholarly journals Paradoxical Enhancement of Spatial Learning Induced by Right Hippocampal Lesion in Rats

Symmetry ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2138
Author(s):  
Yukitoshi Sakaguchi ◽  
Yoshio Sakurai
Keyword(s):  
Spatial Learning ◽  
Hippocampal Lesion ◽  
Brain Dysfunction ◽  
Learning Performance ◽  
Lesion Group ◽  
Hippocampal Damage ◽  
Hemispheric Differences ◽  
Brain Functions ◽  
Significant Difference ◽  
The Right

The left–right hemispheric differences in some brain functions are well known in humans. Among them, savant syndrome has unique features, such as exceptional abilities in vision, memory, computation, and music, despite brain abnormalities. In cases of acquired savant and transient savant, brain damage or inhibition is often seen in the left hemisphere, suggesting a link between left hemispheric dysfunction and these talents. On the other hand, some functional left–right differences have been reported in rodent brains, and therefore, unilateral damage in rodents may also result in savant-like enhancements. In the present study, we examined the effects of hippocampal damage on spatial learning in rats with left, right, or bilateral hippocampal lesion. The results showed that learning performance was impaired in the bilateral lesion group, and there was no significant difference in the left lesion group, while performance was enhanced in the right lesion group. These results suggest that damage to the right hippocampus in rats may lead to savant-like enhancement in learning and memory. The construction of the savant model through these results will contribute to the neuroscientific elucidation of the paradoxical phenomenon observed in savants, that some abilities are enhanced despite their brain dysfunction.

scholarly journals Regional microglial activation in the substantia nigra is linked with fatigue in MS

2020 ◽  
Vol 7 (5) ◽  
pp. e854 ◽  
Author(s):  
Tarun Singhal ◽  
Steven Cicero ◽  
Hong Pan ◽  
Kelsey Carter ◽  
Shipra Dubey ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Microglial Activation ◽  
Statistical Parametric Mapping ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
Fatigue Score ◽  
Impact Scale ◽  
Level Of Significance ◽  
The Right

ObjectiveThe goal of our study is to assess the role of microglial activation in MS-associated fatigue (MSAF) using [F-18]PBR06-PET.MethodsFatigue severity was measured using the Modified Fatigue Impact Scale (MFIS) in 12 subjects with MS (7 relapsing-remitting and 5 secondary progressive) and 10 healthy control participants who underwent [F-18]PBR06-PET. The MFIS provides a total fatigue score as well as physical, cognitive, and psychosocial fatigue subscale scores. Standardized Uptake Value (SUV) 60–90 minute frame PET maps were coregistered to 3T MRI. Voxel-by-voxel analysis using Statistical Parametric Mapping and atlas-based regional analyses were performed. SUV ratios (SUVRs) were global brain normalized.ResultsPeak voxel-based level of significance for correlation between total fatigue score and PET uptake was localized to the right substantia nigra (T-score 4.67, p = 0.001). Similarly, SUVRs derived from atlas-based segmentation of the substantia nigra showed significant correlation with MFIS (r = 0.76, p = 0.004). On multiple regression, the right substantia nigra was an independent predictor of total MFIS (p = 0.02) and cognitive MFIS subscale values (p = 0.007), after adjustment for age, disability, and depression. Several additional areas of significant correlations with fatigue scores were identified, including the right parahippocampal gyrus, right precuneus, and juxtacortical white matter (all p < 0.05). There was no correlation between fatigue scores and brain atrophy and lesion load in patients with MS.ConclusionSubstantia nigra microglial activation is linked to fatigue in MS. Microglial activation across key brain regions may represent a unifying mechanism for MSAF, and further evaluation of neuroimmunologic basis of MSAF is warranted.

scholarly journals Impact of cannabis use on thalamic volume in people at familial high risk of schizophrenia

2011 ◽  
Vol 199 (5) ◽  
pp. 386-390 ◽  
Author(s):  
Killian A. Welch ◽  
Andrew C. Stanfield ◽  
Andrew M. McIntosh ◽  
Heather C. Whalley ◽  
Dominic E. Job ◽  
...  
Keyword(s):  
High Risk ◽  
Repeated Measures ◽  
Illicit Drugs ◽  
Subsequent Development ◽  
Volume Loss ◽  
Point Of Entry ◽  
High Genetic Risk ◽  
The Right ◽  
Hippocampal Complex ◽  
Familial High Risk

BackgroundNo longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia.AimsTo examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia.MethodMagnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n= 25) and not exposed (n= 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance.ResultsCannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F= 4.47,P= 0.04) and highly significant on the right (F=7.66,P=0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis.ConclusionsThese are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

scholarly journals Berberine Promotes TREM2-Dependent Phagocytosis of Amyloid-β By Microglia

2021 ◽  
Author(s):  
Yang-Yang Wang ◽  
Zhen-Ting Huang ◽  
Qian Zou ◽  
Yin-Shuang Pu ◽  
Ming-Hao Yuan ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Microglial Activation ◽  
Amyloid Β ◽  
Spatial Learning And Memory ◽  
Pathological Feature ◽  
Bv2 Cells ◽  
Aβ Clearance

Abstract Background: The production and accumulation of amyloid-β (Aβ) is the most important pathological feature of Alzheimer’s Disease (AD), and the deficiency of Aβ clearance contributes to the progression of AD. TREM2-dependent microglial activation may be the key to Aβ clearance. BBR plays the neuroprotective role in the progression of AD by inhibiting Aβ production and promoting Aβ degradation. However, the specific relationship between BBR and microglial activation remains unclear. Thus, we aimed to investigate whether BBR can inhibit the pathological progression of Aβ in AD by changing the phenotype of microglia.Methods: Western blot and Immunofluorescence staining were applied to detect the effects of BBR on the transformation of resting microglia to different phenotypes. ELISA, Immunohistochemistry and Immunofluorescence were used to detect the effect of BBR on microglial phagocytosis of Aβ. Morris water maze (MWM) test was applied to test the effect of BBR on the spatial learning and memory of experimental animals.Results: Firstly, BBR promoted the phagocytosis of Aβ1-42 by BV2 cells. Secondly, BBR promoted the changes of microglia to phenotypes M2 and DAM in vivo and in vitro, which were in close proximity to Aβ and reduced Aβ aggregation. Finally, BBR ameliorated spatial learning and memory impairment in APP/PS1 mice.Conclusion: BBR could enhance the phagocytosis of microglia, which decreased Aβ level and improved the spatial learning and memory of APP/PS1 mice.

scholarly journals Longitudinal Microglial Activation in Tau Transgenic P301S Mice Predicts Increased Tau Accumulation and Deteriorated Spatial Learning

2020 ◽  
Author(s):  
Florian Eckenweber ◽  
Jose Medina Luque ◽  
Tanja Blume ◽  
Christian Sacher ◽  
Gloria Biechele ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Spatial Learning ◽  
Microglial Activation ◽  
Amyloid Β ◽  
Learning Performance ◽  
Wild Type ◽  
Tspo Expression

Abstract Background: P301S tau transgenic mice show age-dependent accumulation of neurofibrillary tangles in brainstem, hippocampus, and neocortex, leading to neuronal loss and cognitive deterioration. However, there is hitherto only sparse documentation of the role of neuroinflammation in tau mouse models. Thus, we analyzed longitudinal microglial activation by small animal 18kDa translocator protein positron-emission-tomography (TSPO µPET) imaging in vivo , in conjunction with terminal assessment of tau pathology, spatial learning, and cerebral glucose metabolism. Methods: Transgenic P301S (n=33) and wild-type (n=18) female mice were imaged by 18 F-GE-180 TSPO µPET at the ages of 1.9, 3.9 and 6.4 months. We conducted behavioral testing in the Morris water maze, 18 F-fluordesoxyglucose ( 18 F-FDG) µPET and AT8 tau immunohistochemistry at 6.3-6.7 months. Terminal microglial immunohistochemistry served for validation of TSPO µPET results in vivo, applying target regions in brainstem, cortex, cerebellum and hippocampus. We compared the results with our historical data in amyloid -β mouse models. Results: TSPO expression in all target regions of P301S mice increased exponentially from 1.9 to 6.4 months, leading to significant differences in the contrasts with wild-type mice at 6.4 months (+11-23%, all p<0.001), but the apparent microgliosis proceeded more slowly than in our experience in amyloid-β mouse models. Spatial learning and glucose metabolism of AT8-positive P301S mice were significantly impaired at 6.3/6.5 months compared to the wild-type group. Longitudinal increases in TSPO expression predicted greater tau accumulation and lesser spatial learning performance at 6.7/6.3 months. Conclusions: Monitoring of microglial activation in P301S tau transgenic mice by TSPO µPET indicates a delayed time course when compared to amyloid-β mouse models. Detrimental associations of microglial activation with outcome parameters are opposite to earlier data in amyloid-β mouse models. The contribution of microglial response to pathology accompanying amyloid-β and tau over-expression merits further investigation.

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