Antibiotics-induced Intestinal Dysbacteriosis Caused Behavioral Alternations and Neuronal Activation in Different Brain Regions in Mice

Abstract Antibiotics affect gut microbial composition, leading to Gut-Brain-Axis imbalance and neurobehavioral changes. However, the intestinal dysbacteriosis associated behavior changes are not consistently reported. It is not clear whether these changes are transient or permanent. The neuroprotective effect of probiotics against intestinal dysbacteriosis induced alternations needs to be determined either. In the present study, oral antibiotic mixture including Ampicillin, Streptomycin, and Clindamycin was utilized to induce intestinal dysbacteriosis in mice. Antibiotics application triggered mechanical allodynia in von frey test and spontaneous pain in open field test. It also resulted in increased anxiety and depressive-like behaviors and damaged spatial memory performance. After application of probiotics, the mechanical allodynia and spontaneous pain were alleviated significantly. The anxiety behaviors, depressive-like behaviors and recognitive performance were ameliorative as well. By using Fos protein as a marker, it is found that the sensory, emotion and memory related brain regions were activated in mice with intestinal dysbacteriosis. Our study is not only helpful for enriching our basic knowledge for understanding the changed pain responses and related brain disorders in antibiotics-induced dysbacteriosis mice, but also beneficial for providing a more comprehensive mechanistic explanation for the regulation of antibiotics and probiotics on gut microbiota and relevant alternations in animal neurological behaviors.

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Antibiotics-induced intestinal dysbacteriosis caused behavioral alternations and neuronal activation in different brain regions in mice

Molecular Brain ◽

10.1186/s13041-021-00759-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Pan Wang ◽

Ke Tu ◽

Peng Cao ◽

Yuefan Yang ◽

Hao Zhang ◽

...

Keyword(s):

Mechanical Allodynia ◽

Neuroprotective Effect ◽

Memory Performance ◽

Mechanistic Explanation ◽

Brain Regions ◽

Basic Knowledge ◽

Spontaneous Pain ◽

Oral Antibiotic ◽

Microbial Composition ◽

Intestinal Dysbacteriosis

AbstractAntibiotics affect gut microbial composition, leading to Gut–Brain-Axis imbalance and neurobehavioral changes. However, the intestinal dysbacteriosis associated behavior changes are not consistently reported. It is not clear whether these changes are transient or permanent. The neuroprotective effect of probiotics against intestinal dysbacteriosis induced alternations needs to be determined either. In the present study, oral antibiotic mixture including Ampicillin, Streptomycin, and Clindamycin was utilized to induce intestinal dysbacteriosis in mice. Antibiotics application triggered mechanical allodynia in von frey test and spontaneous pain in open field test. It also resulted in increased anxiety and depressive-like behaviors and damaged spatial memory performance. After application of probiotics, the mechanical allodynia and spontaneous pain were alleviated significantly. The anxiety behaviors, depressive-like behaviors and recognitive performance were ameliorative as well. By using Fos protein as a marker, it is found that the sensory, emotion and memory related brain regions were activated in mice with intestinal dysbacteriosis. Our study is not only helpful for enriching our basic knowledge for understanding the changed pain responses and related brain disorders in antibiotics-induced dysbacteriosis mice, but also beneficial for providing a more comprehensive mechanistic explanation for the regulation of antibiotics and probiotics on gut microbiota and relevant alternations in animal neurological behaviors.

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Inefficient Encoding as an Explanation for Age-Related Deficits in Recollection-Based Processing

Journal of Psychophysiology ◽

10.1027/0269-8803/a000122 ◽

2014 ◽

Vol 28 (3) ◽

pp. 148-161 ◽

Cited By ~ 12

Author(s):

David Friedman ◽

Ray Johnson

Keyword(s):

Older Adults ◽

Young Adults ◽

Cognitive Processes ◽

Brain Activity ◽

Memory Performance ◽

Brain Regions ◽

Semantic Retrieval ◽

Age Related ◽

The Face ◽

Episodic Memories

A cardinal feature of aging is a decline in episodic memory (EM). Nevertheless, there is evidence that some older adults may be able to “compensate” for failures in recollection-based processing by recruiting brain regions and cognitive processes not normally recruited by the young. We review the evidence suggesting that age-related declines in EM performance and recollection-related brain activity (left-parietal EM effect; LPEM) are due to altered processing at encoding. We describe results from our laboratory on differences in encoding- and retrieval-related activity between young and older adults. We then show that, relative to the young, in older adults brain activity at encoding is reduced over a brain region believed to be crucial for successful semantic elaboration in a 400–1,400-ms interval (left inferior prefrontal cortex, LIPFC; Johnson, Nessler, & Friedman, 2013 ; Nessler, Friedman, Johnson, & Bersick, 2007 ; Nessler, Johnson, Bersick, & Friedman, 2006 ). This reduced brain activity is associated with diminished subsequent recognition-memory performance and the LPEM at retrieval. We provide evidence for this premise by demonstrating that disrupting encoding-related processes during this 400–1,400-ms interval in young adults affords causal support for the hypothesis that the reduction over LIPFC during encoding produces the hallmarks of an age-related EM deficit: normal semantic retrieval at encoding, reduced subsequent episodic recognition accuracy, free recall, and the LPEM. Finally, we show that the reduced LPEM in young adults is associated with “additional” brain activity over similar brain areas as those activated when older adults show deficient retrieval. Hence, rather than supporting the compensation hypothesis, these data are more consistent with the scaffolding hypothesis, in which the recruitment of additional cognitive processes is an adaptive response across the life span in the face of momentary increases in task demand due to poorly-encoded episodic memories.

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Resting‐State EEG Microstates Parallel Age‐Related Differences in Allocentric Spatial Working Memory Performance

Brain Topography ◽

10.1007/s10548-021-00835-3 ◽

2021 ◽

Author(s):

Adeline Jabès ◽

Giuliana Klencklen ◽

Paolo Ruggeri ◽

Christoph M. Michel ◽

Pamela Banta Lavenex ◽

...

Keyword(s):

Older Adults ◽

Working Memory ◽

Resting State ◽

Cognitive Aging ◽

Temporal Dynamics ◽

Spatial Working Memory ◽

Brain Activity ◽

Memory Performance ◽

Brain Regions ◽

Age Related

AbstractAlterations of resting-state EEG microstates have been associated with various neurological disorders and behavioral states. Interestingly, age-related differences in EEG microstate organization have also been reported, and it has been suggested that resting-state EEG activity may predict cognitive capacities in healthy individuals across the lifespan. In this exploratory study, we performed a microstate analysis of resting-state brain activity and tested allocentric spatial working memory performance in healthy adult individuals: twenty 25–30-year-olds and twenty-five 64–75-year-olds. We found a lower spatial working memory performance in older adults, as well as age-related differences in the five EEG microstate maps A, B, C, C′ and D, but especially in microstate maps C and C′. These two maps have been linked to neuronal activity in the frontal and parietal brain regions which are associated with working memory and attention, cognitive functions that have been shown to be sensitive to aging. Older adults exhibited lower global explained variance and occurrence of maps C and C′. Moreover, although there was a higher probability to transition from any map towards maps C, C′ and D in young and older adults, this probability was lower in older adults. Finally, although age-related differences in resting-state EEG microstates paralleled differences in allocentric spatial working memory performance, we found no evidence that any individual or combination of resting-state EEG microstate parameter(s) could reliably predict individual spatial working memory performance. Whether the temporal dynamics of EEG microstates may be used to assess healthy cognitive aging from resting-state brain activity requires further investigation.

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Effects of amnesia on processing in the hippocampus and default mode network during a naturalistic memory task: a case study

10.31234/osf.io/e9n8c ◽

2018 ◽

Author(s):

Christiane Oedekoven ◽

James L. Keidel ◽

Stuart Anderson ◽

Angus Nisbet ◽

Chris Bird

Keyword(s):

Functional Connectivity ◽

Episodic Memory ◽

Memory Performance ◽

Memory Task ◽

Structural Mri ◽

Brain Regions ◽

Left Hippocampus ◽

Cortical Regions ◽

The Right ◽

Encoding And Retrieval

Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of lifelike events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis revealed that in controls the functional connectivity between these regions when watching the videos was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of multimodal representations of the contents of an event.

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Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer’s disease

10.1101/2020.05.11.089383 ◽

2020 ◽

Author(s):

Xiong Jiang ◽

James H. Howard ◽

G. Wiliam Rebeck ◽

R. Scott Turner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Medial Temporal Lobe ◽

Inhibition Of Return ◽

Memory Performance ◽

Brain Regions ◽

List Type ◽

Older Individuals

ABSTRACTSpatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here we provide evidence supporting that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD), and the impairment is readily detectable using a novel double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the novel double cue spatial IOR paradigm may be useful in detecting MCI and early AD.SIGNIFICANCE STATEMENTNovel double cue spatial inhibition of return (IOR) paradigm revealed a robust effect IOR deficits in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD)Spatial IOR effect correlates with memory performance in healthy older adults at a elevated risk of Alzheimer’s disease (with a family history or APOE e4 allele)The data suggests that double cue spatial IOR may be sensitive to detect early AD pathological changes, which may be linked to disease progress at the posterior brain regions (rather than the medial temporal lobe)

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Neuroprotective Effects of Alisol A 24-acetate on Cerebral Ischemia-reperfusion Injury by Regulating PI3K/AKT Pathway

10.21203/rs.3.rs-927256/v1 ◽

2021 ◽

Author(s):

Taotao Lu ◽

Huihong Li ◽

Yangjie Zhou ◽

Wei Wei ◽

Linlin Ding ◽

...

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion Injury ◽

Neuroprotective Effect ◽

Ischemia Reperfusion ◽

Brain Regions ◽

Global Cerebral Ischemia ◽

Akt Pathway ◽

Object Recognition Test ◽

Neuroprotective Effects ◽

Cerebral Ischemia Reperfusion

Abstract BackgroundNeuroinflammation and apoptosis are involved in the pathogenesis of ischemic stroke. Alisol A 24-acetate (24A) has a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A in the global cerebral ischemia/ reperfusion (GCI/R) is still unclear. Methods GCI/R mice was used to investigated the neuroprotective effect of 24A. Modified neurological deficit scores, Morris Water Maze and object recognition test were used to evaluate behaviors. The metabolism in brain regions was detected by MRS. The changes of microglia, astrocytes and neurons was detected. The inflammation and apoptosis were measured.Results The results showed that 24A improved behavioral dysfunction and brain metabolism, alleviate neuroinflammation and apoptosis, inhibited microglia and astrocytes activation, which is associated with the activation of PI3K/AKT pathway. ConclusionsTaken together, our study demonstrated that 24A could alleviate GCI/R injury through anti-neuroinflammation and anti-apoptosis via regulating the PI3K/AKT pathway.

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0421 Decreased Actigraphic Daytime Activity is Associated with Lower Memory Performance in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer’s Disease

SLEEP ◽

10.1093/sleep/zsaa056.418 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A161-A161

Author(s):

E Pardilla-Delgado ◽

L Ramirez Gomez ◽

A Y Baena ◽

M I Montes ◽

Y Bocanegra ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Performance ◽

Word List ◽

Brain Regions ◽

Future Research ◽

Daytime Activity ◽

Mutation Carriers ◽

Wrist Actigraphy ◽

Circadian Dysfunction

Abstract Introduction Alzheimer’s disease (AD) impacts brain regions that control circadian regulation systems such as wakefulness and daytime physical activity. Recent evidence shows that AD pathology is damaging for wake-promoting neurons. Whether early changes in wakefulness and daytime activity occur during asymptomatic stages of familial AD (fAD) remains unknown. In this study, we aimed to investigate whether daytime activity differs between cognitively-unimpaired carriers of early-onset fAD and age-matched non-carrier family members. Further, we examined the associations between daytime activity and memory performance. Methods A total of 25 members of the large Colombian kindred with the Presenilin1 (PSEN1) E280A mutation were included in the study (9 mutation carriers and 16 non-carriers, mean age=38.2). PSEN1 mutation carriers develop dementia before the age of 50. All subjects underwent wrist actigraphy for 7-14 days to measure daytime activity (average activity per minute and per epoch), and completed the CERAD Word List Learning and the Free and Cued Selective Reminding Test (FCSRT). Results Compared to non-carriers, mutation carriers had less average daytime activity (Mann-Whitney U Test p=.04). Higher average daytime activity was associated with better memory recall in both the CERAD word list delayed recall (r=.47, p=.05) and the FCRST delayed total recall (r=.53, p=.02). No associations with age were observed. Conclusion Our results suggest that cognitively-unimpaired mutation carriers have reduced daytime activity, years before the onset of dementia. Reduced daytime activity in carriers is also associated with lower memory performance. Our preliminary findings add to the growing evidence that circadian dysfunction is present in early AD, and may play an important role in subsequent memory impairment. Future research with large samples is needed to further examine sleep and circadian dysfunction in asymptomatic individuals at genetic risk for AD. Support NIA 5R01AG054671-03 to YTQ

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Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson’s Disease: A Comparative Study

Antioxidants ◽

10.3390/antiox9010049 ◽

2020 ◽

Vol 9 (1) ◽

pp. 49 ◽

Cited By ~ 3

Author(s):

Lyubka P. Tancheva ◽

Maria I. Lazarova ◽

Albena V. Alexandrova ◽

Stela T. Dragomanova ◽

Ferdinando Nicoletti ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuroprotective Effect ◽

Memory Performance ◽

Natural Antioxidants ◽

Control Group ◽

Biochemical Assays ◽

Male Wistar Rats ◽

Improved Learning ◽

6 Hydroxydopamine

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson’s disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

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Brain Activity in Self- and Value-Related Regions in Response to Online Antismoking Messages Predicts Behavior Change

Journal of Media Psychology Theories Methods and Applications ◽

10.1027/1864-1105/a000146 ◽

2015 ◽

Vol 27 (3) ◽

pp. 93-109 ◽

Cited By ~ 35

Author(s):

Nicole Cooper ◽

Steve Tompson ◽

Matthew Brook O’Donnell ◽

B. Falk Emily

Keyword(s):

Behavior Change ◽

Risk Perceptions ◽

Brain Activity ◽

Smoking Behavior ◽

Mechanistic Explanation ◽

Health Behavior Change ◽

Brain Regions ◽

Self Report ◽

Traditional Theory ◽

And Behavior

Abstract. In this study, we combined approaches from media psychology and neuroscience to ask whether brain activity in response to online antismoking messages can predict smoking behavior change. In particular, we examined activity in subregions of the medial prefrontal cortex linked to self- and value-related processing, to test whether these neurocognitive processes play a role in message-consistent behavior change. We observed significant relationships between activity in both brain regions of interest and behavior change (such that higher activity predicted a larger reduction in smoking). Furthermore, activity in these brain regions predicted variance independent of traditional, theory-driven self-report metrics such as intention, self-efficacy, and risk perceptions. We propose that valuation is an additional cognitive process that should be investigated further as we search for a mechanistic explanation of the relationship between brain activity and media effects relevant to health behavior change.

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Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

Neurology ◽

10.1212/wnl.0000000000007728 ◽

2019 ◽

Vol 93 (1) ◽

pp. e29-e39 ◽

Cited By ~ 13

Author(s):

Val J. Lowe ◽

Tyler J. Bruinsma ◽

Heather J. Wiste ◽

Hoon-Ki Min ◽

Stephen D. Weigand ◽

...

Keyword(s):

Entorhinal Cortex ◽

Medial Temporal Lobe ◽

Memory Performance ◽

Standardized Uptake Value ◽

Brain Regions ◽

Population Based ◽

Cognitive Test ◽

Amyloid Pet ◽

Cross Sectional ◽

Tau Pet

ObjectiveTo assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults.MethodsTau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49.ResultsHigher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+.ConclusionsTau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

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