Anxiety and Alzheimer’s disease: Behavioral analysis and neural basis in rodent models of Alzheimer’s-related neuropathology

Pentkowski, Nathan S.; Rogge-Obando, Kimberly; Donaldson, Tia N.; Bouquin, Samuel J.; Clark, Benjamin J.

doi:10.1016/j.neubiorev.2021.05.005

Cited by 61 publications

(36 citation statements)

References 259 publications

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“…In db/db mice, we detected a functional disturbance in emotion that corresponds to Alzheimer's-disease-like pathology [46], namely, anxiety in the elevated plus-maze and open field tests and its good alleviation due to trehalose application. There was also a recovery of exploratory and locomotor activity as assessed by the open field test.…”

Section: Discussionmentioning

confidence: 95%

Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice

Короленко¹,

Дубровина²,

Ovsyukova³

et al. 2021

Cells

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Autophagy attenuation has been found in neurodegenerative diseases, aging, diabetes mellitus, and atherosclerosis. In experimental models of neurodegenerative diseases, the correction of autophagy in the brain reverses neuronal and behavioral deficits and hence seems to be a promising therapy for neuropathologies. Our aim was to study the effect of an autophagy inducer, trehalose, on brain autophagy and behavior in a genetic model of diabetes with signs of neuronal damage (db/db mice). A 2% trehalose solution was administered as drinking water during 24 days of the experiment. Expressions of markers of autophagy (LC3-II), neuroinflammation (IBA1), redox state (NOS), and neuronal density (NeuN) in the brain were assessed by immunohistochemical analysis. For behavioral phenotyping, the open field, elevated plus-maze, tail suspension, pre-pulse inhibition, and passive avoidance tests were used. Trehalose caused a slight reduction in increased blood glucose concentration, considerable autophagy activation, and a decrease in the neuroinflammatory response in the brain along with improvements of exploration, locomotor activity, anxiety, depressive-like behavior, and fear learning and memory in db/db mice. Trehalose exerted some beneficial peripheral and systemic effects and partially reversed behavioral alterations in db/db mice. Thus, trehalose as an inducer of mTOR-independent autophagy is effective at alleviating neuronal and behavioral disturbances accompanying experimental diabetes.

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Section: Discussionmentioning

confidence: 95%

Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice

Короленко¹,

Дубровина²,

Ovsyukova³

et al. 2021

Cells

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“…Oxidative disbalance is known to be associated with anxiety [62][63][64], which, in its turn, is often considered an early marker or risk factor for Alzheimer's disease [65][66][67]. This and other neurodegenerative diseases, characterized by the reduced redox status of the brain, also exhibit the decreased activity of the brain OGDHC, already at the initial study of the disease [68].…”

Section: Discussionmentioning

confidence: 99%

Increasing Inhibition of the Rat Brain 2-Oxoglutarate Dehydrogenase Decreases Glutathione Redox State, Elevating Anxiety and Perturbing Stress Adaptation

et al. 2022

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Specific inhibitors of mitochondrial 2-oxoglutarate dehydrogenase (OGDH) are administered to animals to model the downregulation of the enzyme as observed in neurodegenerative diseases. Comparison of the effects of succinyl phosphonate (SP, 0.02 mmol/kg) and its uncharged precursor, triethyl succinyl phosphonate (TESP, 0.02 and 0.1 mmol/kg) reveals a biphasic response of the rat brain metabolism and physiology to increasing perturbation of OGDH function. At the low (TE)SP dose, glutamate, NAD+, and the activities of dehydrogenases of 2-oxoglutarate and malate increase, followed by their decreases at the high TESP dose. The complementary changes, i.e., an initial decrease followed by growth, are demonstrated by activities of pyruvate dehydrogenase and glutamine synthetase, and levels of oxidized glutathione and citrulline. While most of these indicators return to control levels at the high TESP dose, OGDH activity decreases and oxidized glutathione increases, compared to their control values. The first phase of metabolic perturbations does not cause significant physiological changes, but in the second phase, the ECG parameters and behavior reveal decreased adaptability and increased anxiety. Thus, lower levels of OGDH inhibition are compensated by the rearranged metabolic network, while the increased levels induce a metabolic switch to a lower redox state of the brain, associated with elevated stress of the animals.

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“…The OFT has been shown to be a relatively non-stressful test (Bodden et al, 2018), and a proper testing order for three unconditioned anxiety tests has been suggested as OFT, LDB, and last, EZM or EPM, with at least a 48-h interval between tests (Tsuda et al, 2020). Employing a combination of conditioned and unconditioned tests has also been suggested (Pentkowski et al, 2021).…”

Section: Use Of Multiple Tests and Alternative Data Analysis Methodsmentioning

confidence: 99%

“…The authors reported that only about 13% of the injured animals were found to be "vulnerable, " showing increased exploration of anxiogenic regions during testing compared to baseline behavior and to sham-treated animals (Popovitz et al, 2021). The behavior of the vulnerable mice had neurobiological correlates in the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus; all areas that are associated with stress and anxiety (Almeida-Suhett et al, 2014;Bryant and Barker, 2020;Kenwood et al, 2021;Liu et al, 2021;McCorkle et al, 2021;Pentkowski et al, 2021). Statz et al employed a different "affective profiling" technique to identify "affected" and "unaffected" rats 3 weeks or 6 months following exposure to repeated blast overpressure (Statz et al, 2019).…”

Section: Use Of Multiple Tests and Alternative Data Analysis Methodsmentioning

confidence: 99%

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury

Tucker

McCabe

2021

Front. Behav. Neurosci.

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Anxiety is a common complaint following acquired traumatic brain injury (TBI). However, the measurement of dysfunctional anxiety behavioral states following experimental TBI in rodents is complex. Some studies report increased anxiety after TBI, whereas others find a decreased anxiety-like state, often described as increased risk-taking behavior or impulsivity. These inconsistencies may reflect a lack of standardization of experimental injury models or of behavioral testing techniques. Here, we review the most commonly employed unconditioned tests of anxiety and discuss them in a context of experimental TBI. Special attention is given to the effects of repeated testing, and consideration of potential sensory and motor confounds in injured rodents. The use of multiple tests and alternative data analysis methods are discussed, as well as the potential for the application of common data elements (CDEs) as a means of providing a format for documentation of experimental details and procedures of each published research report. CDEs may improve the rigor, reproducibility, as well as endpoint for better relating findings with clinical TBI phenotypes and the final goal of translation. While this may not resolve all incongruities in findings across laboratories, it is seen as a way forward for standardized and universal data collection for improvement of data quality and sharing, and advance therapies for neuropsychiatric symptoms that often present for decades following TBI.

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Anxiety and Alzheimer’s disease: Behavioral analysis and neural basis in rodent models of Alzheimer’s-related neuropathology

Cited by 61 publications

References 259 publications

Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice

Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice

Increasing Inhibition of the Rat Brain 2-Oxoglutarate Dehydrogenase Decreases Glutathione Redox State, Elevating Anxiety and Perturbing Stress Adaptation

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury

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