Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Siedhoff, Heather R.; Chen, Shanyan; Balderrama, Ashley; Sun, Grace Y.; Koopmans, Bastijn; DePalma, Ralph G.; Cui, Jiankun; Z, Gu

doi:10.1089/neur.2021.0063

Cited by 7 publications

(8 citation statements)

References 47 publications

(65 reference statements)

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“…The results of these studies show a correlation >0.9 between NREM and REM sleep, on the hand, and the animals being still ≥40s, on the other. This behavioural criterion for sleep has subsequently been used in a number of studies [51][52][53][54][55]. We conclude based on our results and those obtained with other HCM techniques (idem) that bouts of inferred sleep (no distinction made here between NREM and REM) in single housed mice of this strain commonly have a duration of 300-400s but can exceed 1000s and occur with an average density of ~120 bouts per day preferentially during lights on.…”

Section: Bouts Of Rest and Pasupporting

confidence: 59%

Bouts of rest and physical activity in C57BL/6J mice

Pernold¹,

Rullman²,

Ulfhake³

2023

Preprint

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The objective was to exploit the raw data output from a scalable home cage (type IIL IVC) monitoring (HCM) system (DVC®), to characterize pattern of undisrupted rest and physical activity (PA) of C57BL/6J mice. The system's tracking algorithm show that mice in isolation spend 67% of the time in bouts of long rest (>=40s) and 59 % of the time was interpreted as sleep. Twenty percent is physical activity (PA), split equally between local movements and locomotion. Decomposition revealed that a day contains ~6500 discrete bouts of short and long rest, local and locomotor movements. Mice travel ~330m per day, mainly during the dark hours, while travelling speed is similar through the light-dark cycle. Locomotor bouts are usually <0.2m and <1% are >1m. Tracking revealed also fits of abnormal behaviour. The starting positions of the bouts showed no preference for the rear over the front of the cage floor, while there was a strong bias for the peripheral (75%) over the central floor area. The composition of bouts has a characteristic circadian pattern, however, intrusive husbandry routines increased bout fragmentation by ~40%. Extracting electrode activations density (EAD) from the raw data yielded results close to those obtained with the tracking algorithm, with 59% of time in long rest (<1 EAD s-1) and 20% in PA. We confirm that EAD correlates closely with movement distance (rs>0.95) and the data agreed in ~96% of the file time. Thus, albeit EAD being less informative it may serve as a proxy for PA and rest, enabling monitoring group housed mice. The data show that a change in housing density from one to two, and up to three mice had the same effect size on EAD (~2) with no difference between sexes. The EAD deviated significantly from this stepwise increase with 4 mice per cage, suggesting a crowdedness stress inducing sex specific adaptations. We conclude that informative metrics on rest and PA can be automatically extracted from the raw data flow in near-real time (< 1 hrs). These metrics relay useful longitudinal information to those that use or care for the animals.

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Section: Bouts Of Rest and Pasupporting

confidence: 59%

Bouts of rest and physical activity in C57BL/6J mice

Pernold¹,

Rullman²,

Ulfhake³

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The results of these studies show a correlation >0.9 between NREM and REM sleep, on the hand, and the animals being still �40s, on the other. This behavioural criterion for sleep has subsequently been used in a number of studies [52][53][54][55][56]. We conclude based on our results on single housed female mice and those obtained with other HCM techniques (idem) that bouts of inferred sleep (no distinction made here between NREM and REM) in single housed mice of this strain commonly have a duration of 300-400s but can exceed 1000s and occur with an average density of ˜120 bouts per day preferentially during lights on.…”

Section: Plos Onesupporting

confidence: 53%

Bouts of rest and physical activity in C57BL/6J mice

2023

View full text Add to dashboard Cite

The objective was to exploit the raw data output from a scalable home cage (type IIL IVC) monitoring (HCM) system (DVC®), to characterize pattern of undisrupted rest and physical activity (PA) of C57BL/6J mice. The system’s tracking algorithm show that mice in isolation spend 67% of the time in bouts of long rest (≥40s). Sixteen percent is physical activity (PA), split between local movements (6%) and locomotion (10%). Decomposition revealed that a day contains ˜7100 discrete bouts of short and long rest, local and locomotor movements. Mice travel ˜330m per day, mainly during the dark hours, while travelling speed is similar through the light-dark cycle. Locomotor bouts are usually <0.2m and <1% are >1m. Tracking revealed also fits of abnormal behaviour. The starting positions of the bouts showed no preference for the rear over the front of the cage floor, while there was a strong bias for the peripheral (75%) over the central floor area. The composition of bouts has a characteristic circadian pattern, however, intrusive husbandry routines increased bout fragmentation by ˜40%. Extracting electrode activations density (EAD) from the raw data yielded results close to those obtained with the tracking algorithm, with 81% of time in rest (<1 EAD s-1) and 19% in PA. Periods ≥40 s of file when no movement occurs and there is no EAD may correspond to periods of sleep (˜59% of file time). We confirm that EAD correlates closely with movement distance (rs>0.95) and the data agreed in ˜97% of the file time. Thus, albeit EAD being less informative it may serve as a proxy for PA and rest, enabling monitoring group housed mice. The data show that increasing density from one female to two males, and further to three male or female mice had the same effect size on EAD (˜2). In contrast, the EAD deviated significantly from this stepwise increase with 4 mice per cage, suggesting a crowdedness stress inducing sex specific adaptations. We conclude that informative metrics on rest and PA can be automatically extracted from the raw data flow in near-real time (< 1 hrs). As discussed, these metrics relay useful longitudinal information to those that use or care for the animals.

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“…The mice were housed in standard home-cages with bedding, maintained on a 12-h light/dark cycle, and provided with ad libitum access to food and water throughout the study period. The open-field LIB exposures were performed at the Missouri University of Science & Technology, following established procedures as previously reported [ 4 , 11 , 13 , 14 , 40 , 43 , 44 , 86 ]. The study included a total of 20 male mice: 10 rTg4510 (RRID: IMSR_JAX:024854) [Tg(CaMKIIa-tTA)/Mmay and Fgf14/Tg(tetO-MAPT·P301L)4510 mice] and 10 non-carrier (RRID: IMSR_JAX:019019) mice in the same C57BL/6J background recommend by and purchased from Jackson Laboratory (Bar Harbor, ME, USA), both aged 2 months.…”

Section: Methodsmentioning

confidence: 99%

“…These mice were found to have hyperphosphorylation of the tau protein in the cortex [ 13 ]. Other behavioral deficits associated with BINT in rodents include anxiety-like behaviors [ 44 ], poor cognition and cognitive flexibility [ 11 ], learning deficits [ 11 ], reduced motor and sensorimotor function [ 12 ], weight loss [ 45 ], and apnea [ 45 ], many of which have been observed in rTg4510 mice [ 22 , 46 ]. Three months following BINT, mice displayed reduced discriminatory learning and reversal learning abilities which correlated with protein expression changes related to synaptic plasticity in the hippocampus [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Chronic Effects of a Single Low-Intensity Blast Exposure on Phosphoproteome Networks and Cognitive Function Influenced by Mutant Tau Overexpression

Jackson,

Chen,

Nguyen

et al. 2024

IJMS

Self Cite

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Blast-induced neurotrauma (BINT) is a pressing concern for veterans and civilians exposed to explosive devices. Affected personnel may have increased risk for long-term cognitive decline and developing tauopathies including Alzheimer’s disease-related disorders (ADRD) or frontal-temporal dementia (FTD). The goal of this study was to identify the effect of BINT on molecular networks and their modulation by mutant tau in transgenic (Tg) mice overexpressing the human tau P301L mutation (rTg4510) linked to FTD or non-carriers. The primary focus was on the phosphoproteome because of the prominent role of hyperphosphorylation in neurological disorders. Discrimination learning was assessed following injury in the subsequent 6 weeks, using the automated home-cage monitoring CognitionWall platform. At 40 days post injury, label-free phosphoproteomics was used to evaluate molecular networks in the frontal cortex of mice. Utilizing a weighted peptide co-expression network analysis (WpCNA) approach, we identified phosphopeptide networks tied to associative learning and mossy-fiber pathways and those which predicted learning outcomes. Phosphorylation levels in these networks were inversely related to learning and linked to synaptic dysfunction, cognitive decline, and dementia including Atp6v1a and Itsn1. Low-intensity blast (LIB) selectively increased pSer262tau in rTg4510, a site implicated in initiating tauopathy. Additionally, individual and group level analyses identified the Arhgap33 phosphopeptide as an indicator of BINT-induced cognitive impairment predominantly in rTg4510 mice. This study unveils novel interactions between ADRD genetic susceptibility, BINT, and cognitive decline, thus identifying dysregulated pathways as targets in potential precision-medicine focused therapeutics to alleviate the disease burden among those affected by BINT.

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Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Cited by 7 publications

References 47 publications

Bouts of rest and physical activity in C57BL/6J mice

Bouts of rest and physical activity in C57BL/6J mice

Bouts of rest and physical activity in C57BL/6J mice

The Chronic Effects of a Single Low-Intensity Blast Exposure on Phosphoproteome Networks and Cognitive Function Influenced by Mutant Tau Overexpression

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