The battery of tests for experimental behavioral phenotyping of aging animals

Gorina, Ya. V.; Kоmleva, Yu. K.; Lopatina, Olga; Volkova, Valentyna; Черных, А. И.; Shabalova, Anna A.; Semenchukov, A. A.; Olovyannikova, R. Ya.; Салмина, А. Б.

doi:10.1134/s2079057017020060

Cited by 12 publications

(15 citation statements)

References 18 publications

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“…Since anxiety is reported to increase in aging rodents [66] and cholinergic manipulations are known to influence anxiety levels [67,68], in the present study we used the EPM as a validated test to measure anxiety in rodents based on their natural aversion for heights and open spaces [39,40,69,70].…”

Section: Elevated Plus Maze (Epm)mentioning

confidence: 99%

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Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

Cutuli

Landolfo

Decandia

et al. 2020

IJMS

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As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 PUFA supplementation on behavioral deficits, hippocampal neurogenesis, volume loss, and astrogliosis in aged mice that underwent a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valid model to mimic a key component of the cognitive deficits associated with dementia. Aged mice were supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks and then cholinergically depleted with mu-p75-saporin immunotoxin. Two weeks after lesioning, mice were behaviorally tested to assess anxious, motivational, social, mnesic, and depressive-like behaviors. Subsequently, morphological and biochemical analyses were performed. In lesioned aged mice the n-3 PUFA pre-treatment preserved explorative skills and associative retention memory, enhanced neurogenesis in the dentate gyrus, and reduced volume and VAChT levels loss as well as astrogliosis in hippocampus. The present findings demonstrating that n-3 PUFA supplementation before cholinergic depletion can counteract behavioral deficits and hippocampal neurodegeneration in aged mice advance a low-cost, non-invasive preventive tool to enhance life quality during aging.

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Section: Elevated Plus Maze (Epm)mentioning

confidence: 99%

“…The SI test is used to investigate social behaviors, which are known to decrease with age in rodents [66,74].…”

Section: Social Interactions (Si)mentioning

confidence: 99%

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

Cutuli

Landolfo

Decandia

et al. 2020

IJMS

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“…To further verify the anti-oxidative and anti-apoptosis properties of TB and SA, the extracts were administered Aβ 25-35 -induced mice. It is considered that the majority of people with AD are older (≥65 years) and as such, the age of experimental animals is a critical variable in experimental research (37). The current study assessed the protective role of PhGs in AD.…”

Section: Discussionmentioning

confidence: 99%

Protective role of phenylethanoid glycosides, Torenoside�B and Savatiside A, in Alzheimer's disease

Zhao

et al. 2019

Exp Ther Med

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The current study assessed the efficacy of two phenylethanoid glycosides (PhGs), Torenoside B (TB) and Savatiside A (SA), in the treatment of Alzheimer's disease (AD). The effects of TB and SA compounds were first assessed following amyloid beta (Aβ) 25-35 induction in SH-SY5Y cells at a range of concentrations. Their effects on cell viability and reactive oxygen species (ROS) were determined by performing MTT and dichlorofluorescin diacetate assays, respectively. The concentration of intracellular Ca 2+ was determined using Fluo-3AM to stain SH-SY5Y cells. SA and TB treatments were also assessed in Aβ 25-35-induced mice. Y-maze and Morris water maze methods were utilized to assess murine learning and memory capability. The pathological changes of murine hippocampi was determined using H&E and Nissl staining. In addition, biochemical parameters associated with intracellular reactive oxygen pathways including Maleic dialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE) and Calnexin were also assessed. TB and SA treatment in Aβ 25-35-induced SH-SY5Y cells resulted in the restoration of cell morphology, an increase of SOD and GSH-Px activity, a decrease in ROS, Ca 2+ and MDA content, and a decrease in Calnexin expression. Furthermore, SA or TB treatment administered to Aβ 25-35-induced mice improved their spatial/non-spatial learning and memory capabilities. The efficacy of treatment was also supported by a marked change in the morphological structure of pyramidal neurons in the CA1 areas of murine hippocampi, as well as an increase of SOD and GSH-Px activity. Treatment also resulted in a decrease in MDA content, AchE activity and Calnexin expression in murine hippocampal tissue. As potential AD treatment drugs, SA and TB compounds have been demonstrated to alleviate the oxidative stress induced by Aβ 25-35 via the regulation of intracellular calcium homeostasis and Calnexin, preventing AD development.

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“…These results indicate that BBB dysfunction appears earlier than has been appreciated, placing it among the earliest known biomarkers of aging in the rodent brain. The onset of BBB dysfunction at around 12 months corresponds with other early biological hallmarks of aging, including the typical onset of reproductive senescence in female mice, as well as the earliest appearance of mild cognitive impairments in various behavior tasks (32)(33)(34)(35)(36)(37). To confirm age-related BBB dysfunction, we raised a separate cohort of aged mice and used an alternate method to quantify BBB permeability, based on detecting leakage of a fluorescent tracer, Evans blue (EB), into the brain after i.v.…”

Section: Progressive Bbb Dysfunction and Albumin Extravasation In Thementioning

confidence: 99%

“…2A; Table S1). We first established normal levels of brain permeability based on permeability values in healthy, young patients (age [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], setting an upper value for "normal permeability" at the 95 th percentile (i.e. 95% of brain voxels in the averaged healthy young brain were below this value).…”

Section: The Aging Human Brain Shows Progressive Bbb Dysfunction Assomentioning

confidence: 99%

Blood-brain barrier dysfunction in aging induces hyper-activation of TGF-beta signaling and chronic yet reversible neural dysfunction

Senatorov

Friedman

Milikovsky

et al. 2019

Preprint

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Aging involves a decline in neural function that contributes to cognitive impairment and disease. However, the mechanisms underlying the transition from a young-and-healthy to aged-anddysfunctional brain are not well understood. Here, we report breakdown of the vascular blood-brain barrier (BBB) in aging humans and rodents, which begins as early as middle age and progresses to the end of the lifespan. Gain-of-function and loss-of-function manipulations show that this BBB dysfunction triggers hyperactivation of transforming growth factor β (TGFβ) signaling in astrocytes, which is necessary and sufficient to cause neural dysfunction and age-related pathology. Specifically, infusion of the serum protein albumin into the young brain (mimicking BBB leakiness) induced astrocytic TGFβ signaling and an aged brain phenotype including aberrant electrocorticographic activity, vulnerability to seizures, and cognitive impairment. Furthermore, conditional genetic knockdown of astrocytic TGFβ receptors, or pharmacological inhibition of TGFβ signaling, reversed these symptomatic outcomes in aged mice. Finally, we found that this same signaling pathway is activated in aging human subjects with BBB dysfunction. Our study identifies dysfunction in the neurovascular unit as one of the earliest triggers of neurological aging, and demonstrates that the aging brain may retain considerable latent capacity which can be revitalized by therapeutic inhibition of TGFβ signaling. cm or less), and percentage of time at the novel object was quantified as (duration investigating novel object) / (total duration investigating all three objects). The set objects were chosen from common items such as lab bottles, pipette boxes, cups (placed open-side down), etc., that were of similar dimensions but varied in shape, color, and material. The sequence and position of objects used across trials was identical for all mice.

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The battery of tests for experimental behavioral phenotyping of aging animals

Cited by 12 publications

References 18 publications

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

Protective role of phenylethanoid glycosides, Torenoside�B and Savatiside A, in Alzheimer's disease

Blood-brain barrier dysfunction in aging induces hyper-activation of TGF-beta signaling and chronic yet reversible neural dysfunction

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