Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse

Scott, Karen A.; Ida, Masayuki; Peterson, Veronica L.; Prenderville, Jack; Moloney, Gerard M.; Izumo, Takayuki; Murphy, Kiera; Murphy, Amy; Ross, R. Paul; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.

doi:10.1016/j.bbi.2017.02.004

Cited by 172 publications

(124 citation statements)

References 81 publications

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“…Increasing age from middle age to old age induces further changes in a wide range of behaviors, such as decreased locomotor activity, increased anxiety‐like behavior, reduced social behavior, decreased ASR, decreased Barnes maze performance, and increased freezing when exposed to the fear‐conditioning context and the altered context. The results of behavioral differences between young and aged male C57BL/6J mice were generally consistent with the previous reports (eg, Refs ). These findings indicate that aging is associated with gradual changes in behaviors related to locomotor activity, anxiety‐like behavior, and memory functions from young to old age.…”

Section: Discussionsupporting

confidence: 92%

“…Consistent with the absence of marked age differences in social behavior in aged mice, the results of the sociability test showed that middle‐ and old‐aged mice, as well as young mice, exhibited a preference for the novel mouse, which suggests that there are no clear differences in neophobic responses to a novel social stimulus, social interest, or sociability among the age groups. In the social novelty preference test conducted immediately after the sociability test, aged mice (17‐ and 23‐months old) exhibited no preference for a new stranger mouse (a decreased social novelty preference), which is consistent with a recent report . The decreased preference for social novelty might reflect a reduced ability to discriminate between individual mice, suggesting that a social recognition deficit is present in aged mice.…”

Section: Discussionsupporting

confidence: 89%

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Age‐related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program

Shoji

Miyakawa

2019

Neuropsychopharm Rep

149

103

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Aim Aging is thought to coincide with gradual and progressive changes in brain function and behavior over the lifetime. Our previous meta‐analytic study reported age‐related behavioral changes from young to middle age in male C57BL/6J mice. However, the previous study had some limitations that could affect the generalizability of the findings because of the potential influence of genetic and environmental factors on behavior, in addition to a lack of information regarding the behaviors of old‐aged mice. Here, to investigate age‐related behavioral changes from young to old age in mice, we analyzed the behaviors of male C57BL/6J mice from four different age groups (8, 47, 73, and 99 weeks of age at the beginning of the experiment) from a colony that had been maintained in a genetically controlled condition based on The Jackson Laboratory's Genetic Stability Program in an environmentally controlled animal facility. Methods We used a battery of behavioral tests, including the light/dark transition, open field, elevated plus maze, hot plate, social interaction, rotarod, three‐chamber social approach, prepulse inhibition, Porsolt forced swim, T‐maze, Barnes maze, tail suspension, and fear‐conditioning tests. Results Some behavioral changes occurred between young and middle age, and further changes in various behaviors were observed in old age. Decreased locomotor activity and increased anxiety‐like behavior were found in old‐aged mice compared to those in young and middle‐aged mice in the light/dark transition test. Similarly, an age‐dependent decrease in locomotor activity was observed in the open field test and the elevated plus maze test, while there was an age‐dependent increase in the time spent in the center area in the open field test and there were no significant differences among age groups in behavioral measures of anxiety in the elevated plus maze test. Decreases in motor performance and the auditory startle response were found in middle‐aged mice compared to those in young mice. Similar behavioral changes and increased pain sensitivity, decreased social novelty preference, reduced working and spatial memory, and impaired cued fear memory were observed in old‐aged mice compared to those in young mice. Prepulse inhibition was higher in middle‐aged mice than in young and old‐aged mice. Age‐related changes in depression‐related behavior were dependent on the type of test and the test time period. Conclusions This study generally confirmed our previous report regarding age‐related behavioral changes from young to middle age and expanded the previous observations by examining the behaviors of old‐aged mice. Our results show age‐related changes in a wide range of behaviors in mice from young to old age. Most behaviors showed gradual changes with advancing age, but some types of behaviors, such as vertical activity, prepulse inhibition, and depression‐related behavior, did not show unidirectional changes with age. These findings provide basic information about the behavioral characteristics of young, middl...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Age‐related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program

Shoji

Miyakawa

2019

Neuropsychopharm Rep

149

103

View full text Add to dashboard Cite

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“…For instance, we have recently characterized the microbiota composition of aged (20–21 months old) versus young (2–3 months old) mice . Aged animals displayed an altered microbiota, with changes observed in phyla that have previously been associated with inflammation, which is consistent with previous reports . Aged animals display increased basal intestinal permeability, which is exacerbated in response to stress.…”

Section: Microbiota and Neurology: Aging And Neurodegenerationsupporting

confidence: 89%

Recent developments in understanding the role of the gut microbiota in brain health and disease

Sherwin

Dinan

Cryan

2017

Annals of the New York Academy of Sciences

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273

164

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There is a growing appreciation of the role of the gut microbiota in all aspects of health and disease, including brain health. Indeed, roles for the bacterial commensals in various psychiatric and neurological conditions, such as depression, autism, stroke, Parkinson's disease, and Alzheimer's disease, are emerging. Microbiota dysregulation has been documented in all of these conditions or in animal models thereof. Moreover, depletion or modulation of the gut microbiota can affect the severity of the central pathology or behavioral deficits observed in a variety of brain disorders. However, the mechanisms underlying such effects are only slowly being unraveled. Additionally, recent preclinical and clinical evidence suggest that targeting the microbiota through prebiotic, probiotic, or dietary interventions may be an effective "psychobiotic" strategy for treating symptoms in mood, neurodevelopmental disorders, and neurodegenerative diseases.

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“…In a observational study considering mice of different ages, these symptoms were correlated with increased gut permeability, increased systemic inflammation and overrepresentation of several bacterial taxa in the cecal microbiota, including Porphyromonadaceae, Odoribacter, Butyricimonas, Clostridium and Oxalobacter , a microbiome profile resembling to that of murine inflammatory bowel disease 41. The presence of gut microbiota dysbiosis also negatively influenced the immunological response and clinical outcomes of experimental mouse models of stroke, resulting in worse motoric and cognitive symptoms than those of mice with a healthy microbiota profile 42…”

Section: Resultsmentioning

confidence: 99%

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

168

133

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Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of “gut–brain axis” has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer’s disease) support the concept of a gut–brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.

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Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse

Cited by 172 publications

References 81 publications

Age‐related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program

Age‐related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program

Recent developments in understanding the role of the gut microbiota in brain health and disease

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

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