Spatial memory and gut microbiota alterations are already present in early-adulthood in a preclinical transgenic model of Alzheimer´s disease

The irreversible and progressive neurodegenerative Alzheimer’s disease (AD) is characterized by cognitive decline, extracellular β-amyloid peptide accumulation, and tau neurofibrillary tangles in the cortex and hippocampus. The triple-transgenic (3xTg) mouse model of AD presents memory impairment in several behavioral paradigms and histopathological alterations from 6 to 16 months old. Additionally, it seems that dysbiotic gut microbiota is present in both mouse models and patients of AD at the cognitive symptomatic stage. The present study aimed to assess spatial learning, memory retention, and gut microbiota alterations in an early adult stage of the 3xTg-AD mice as well as to explore its sexual dimorphism. We evaluated motor activity, novel-object localization training, and retention test as well as collected fecal samples to characterize relative abundance, alpha- and beta-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) analysis in gut microbiota in both female and male 3xTg-AD mice, and controls [non-transgenic mice (NoTg)], at 3 and 5 months old. We found spatial memory deficits in female and male 3xTg-AD but no alteration neither during training nor in motor activity. Importantly, already at 3 months old, we observed decreased relative abundances of Actinobacteria and TM7 in 3xTg-AD compared to NoTg mice, while the beta diversity of gut microbiota was different in female and male 3xTg-AD mice in comparison to NoTg. Our results suggest that gut microbiota modifications in 3xTg-AD mice anticipate and thus could be causally related to cognitive decline already at the early adult age of AD. We propose that microbiota alterations may be used as an early and non-invasive diagnostic biomarker of AD.

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Neonatal exposure to androgens dynamically alters gut microbiota architecture

Journal of Endocrinology ◽

10.1530/joe-20-0277 ◽

2020 ◽

Vol 247 (1) ◽

pp. 69-85

Author(s):

Alexia Barroso ◽

Jose Antonio Santos-Marcos ◽

Cecilia Perdices-Lopez ◽

Ana Vega-Rojas ◽

Miguel Angel Sanchez-Garrido ◽

...

Keyword(s):

Gut Microbiota ◽

Early Adulthood ◽

Metabolic Programming ◽

Female Rats ◽

Sex Steroid ◽

Postnatal Life ◽

Metabolic Derangement ◽

Control Male ◽

Male And Female Rats ◽

The Individual

Gonadal steroids strongly contribute to the metabolic programming that shapes the susceptibility to the manifestation of diseases later in life, and the effect is often sexually dimorphic. Microbiome signatures, together with metabolic traits and sex steroid levels, were analyzed at adulthood in neonatally androgenized female rats, and compared with those of control male and female rats. Exposure of female rats to high doses of androgens on early postnatal life resulted in persistent alterations of the sex steroid profile later on life, namely lower progesterone and higher estradiol and estrone levels, with no effect on endogenous androgens. Neonatally androgenized females were heavier (10% at early adulthood and 26% at adulthood) than controls and had impaired glucose homeostasis observed by higher AUC of glucose in GTT and ITT when subjected to obesogenic manipulations. Androgenized female displayed overt alterations in gut microbiota, indicated especially by higher Bacteroidetes and lower Firmicutes abundance at early adulthood, which disappeared when animals were concurrently overfed at adulthood. Notably, these changes in gut microbiota were related with the intestinal expression of several miRNAs, such as miR-27a-3p, miR-29a-5p, and miR-100-3p. Our results suggest that nutritional and hormonal disruption at early developmental periods not only alters the metabolic programming of the individual later in life but also perturbs the architecture of gut microbiota, which may interact with the host by a cross-talk mediated by intestinal miRNAs; phenomena that may contribute to amplify the metabolic derangement caused by obesity, as seen in neonatally androgenized female rats.

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Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18–25 years) with corresponding changes in gut bacterial composition

Scientific Reports ◽

10.1038/s41598-021-87865-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nicola Johnstone ◽

Chiara Milesi ◽

Olivia Burn ◽

Bartholomeus van den Bogert ◽

Arjen Nauta ◽

...

Keyword(s):

Gut Microbiota ◽

Early Adulthood ◽

Later Life ◽

Well Being ◽

Transitional Period ◽

Double Blind ◽

Effective Interventions ◽

Health Related ◽

High Trait Anxiety ◽

Healthy Females

AbstractCurrent research implicates pre- and probiotic supplementation as a potential tool for improving symptomology in physical and mental ailments, which makes it an attractive concept for clinicians and consumers alike. Here we focus on the transitional period of late adolescence and early adulthood during which effective interventions, such as nutritional supplementation to influence the gut microbiota, have the potential to offset health-related costs in later life. We examined multiple indices of mood and well-being in 64 healthy females in a 4-week double blind, placebo controlled galacto-oligosaccharides (GOS) prebiotic supplement intervention and obtained stool samples at baseline and follow-up for gut microbiota sequencing and analyses. We report effects of the GOS intervention on self-reported high trait anxiety, attentional bias, and bacterial abundance, suggesting that dietary supplementation with a GOS prebiotic may improve indices of pre-clinical anxiety. Gut microbiota research has captured the imagination of the scientific and lay community alike, yet we are now at a stage where this early enthusiasm will need to be met with rigorous research in humans. Our work makes an important contribution to this effort by combining a psychobiotic intervention in a human sample with comprehensive behavioural and gut microbiota measures.

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The role of the gut microbiota and nutrition on spatial learning and spatial memory: a mini review based on animal studies

Molecular Biology Reports ◽

10.1007/s11033-021-07078-2 ◽

2022 ◽

Author(s):

Seyyed Mohammad Amin Alemohammad ◽

Seyed Mohammad Reza Noori ◽

Ehsan Samarbafzadeh ◽

Seyyed Mohammad Ali Noori

Keyword(s):

Gut Microbiota ◽

Spatial Memory ◽

Spatial Learning ◽

Animal Studies

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Review for "Anti‐Lingo ‐1 antibody ameliorates spatial memory and synapse loss induced by chronic stress"

10.1002/cne.25038/v1/review2 ◽

2020 ◽

Keyword(s):

Spatial Memory ◽

Chronic Stress ◽

Synapse Loss

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Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_pers-sig5-2019-0002 ◽

2019 ◽

Vol 4 (4) ◽

pp. 633-640 ◽

Cited By ~ 1

Author(s):

Canice E. Crerand ◽

Ari N. Rabkin

Keyword(s):

Cognitive Abilities ◽

Psychotic Disorders ◽

Developmental Stages ◽

Early Adulthood ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Psychosocial Risks ◽

Empirically Supported ◽

Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

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