Individually ventilated cages cause chronic low-grade hypoxia impacting mice hematologically and behaviorally

York, James L.; McDaniel, A.W.; Blevins, Neil A.; Guillet, R.; Allison, Sarah O; Cengel, Keith A.; Freund, Gregory G.

doi:10.1016/j.bbi.2012.04.008

Cited by 26 publications

(19 citation statements)

References 48 publications

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“…This figure shows that after lipopolysaccharide (LPS) administration, mice housed in individually ventilated caging (IVC) recover short-term locomotor activity faster than mice housed in ambient environment caging (AEC) 6 . While the initial loss of locomotor activity is similar between LPS injected groups, the recovery to basal LMA is more rapid in IVC-housed mice as was velocity of movement (Figure 1b) and duration of movement (Figure 1c).…”

Section: Representative Resultsmentioning

confidence: 99%

Mouse Short- and Long-term Locomotor Activity Analyzed by Video Tracking Software

York

Blevins

McNeil

et al. 2013

JoVE

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Locomotor activity (LMA) is a simple and easily performed measurement of behavior in mice and other rodents. Improvements in video tracking software (VTS) have allowed it to be coupled to LMA testing, dramatically improving specificity and sensitivity when compared to the line crossings method with manual scoring. In addition, VTS enables high-throughput experimentation. While similar to automated video tracking used for the open field test (OFT), LMA testing is unique in that it allows mice to remain in their home cage and does not utilize the anxiogenic stimulus of bright lighting during the active phase of the light-dark cycle. Traditionally, LMA has been used for short periods of time (mins), while longer movement studies (hrs-days) have often used implanted transmitters and biotelemetry. With the option of real-time tracking, long-, like short-term LMA testing, can now be conducted using videography. Long-term LMA testing requires a specialized, but easily constructed, cage so that food and water (which is usually positioned on the cage top) does not obstruct videography. Importantly, videography and VTS allows for the quantification of parameters, such as path of mouse movement, that are difficult or unfeasible to measure with line crossing and/or biotelemetry. In sum, LMA testing coupled to VTS affords a more complete description of mouse movement and the ability to examine locomotion over an extended period of time. Video LinkThe video component of this article can be found at http://www.jove.com/video/50252/ Protocol 1. Short-term LMA Set Up and Procedure 1. Short-term LMA cage set up 1. Test short-term LMA within the home cage of a single-housed mouse. To facilitate VTS-dependent image analysis, use bedding in high contrast with mouse color (i.e. dark colored bedding for white mice and light colored bedding for black mice). 2. During short-term LMA testing, cover cages with clear ¼ in Plexiglas with 11 x ¼ in diameter holes to support appropriate ventilation.2. Short-term LMA testing room 1. Test mice in a clean environment in which they have been acclimated to for at least 24 hr 8 . 2. To illuminate the testing environment, use brooder clamp lights with red bulbs (< 125 lumens). Prior to videography, adjust the angle and position of the lights to remove glare or reflections from the Plexiglas cage tops. 3. Remove or avoid room noise above 70 dB. Use a white noise generator if intermittent background noise is unavoidable during mouse testing. 4. Cover the testing surface upon which the cages are placed in the testing room with butcher or lab bench paper of similar color to the cage bedding, in case the cage floor is exposed during videography.3. Short-term LMA videography 1. Center and place a ceiling-mounted night vision-capable video camera with at least 120 GB of memory above the recording area in the testing room. Do not exceed the resolution capability of the VTS used by placing too many cages within the video camera view frame (e.g. Ethovision XT 7 by Noldus Information Technology (Leesbu...

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Section: Representative Resultsmentioning

confidence: 99%

Mouse Short- and Long-term Locomotor Activity Analyzed by Video Tracking Software

York

Blevins

McNeil

et al. 2013

JoVE

Self Cite

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“…Brain regions were dissected from PBS perfused whole brains and RNA was isolated (York et al, 2012b). RNA was reverse transcribed using the High-Capacity cDNA Reverse Transcription Kit (PN 4368813) (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice

Kaczmarczyk

Machaj

Chiu

et al. 2013

Psychoneuroendocrinology

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106

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The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1–3 wks) of a high-fat diet (HFD). After 1 wk of a HFD feeding, mouse burrowing and spontaneous wheel running were increased while mouse exploration of the open quadrants of a zero maze, perfect alternations in a Y-maze and recognition of a novel object were impaired. Examination of mouse cortex, hippocampus and hypothalamus for dopamine and its metabolites demonstrated increased homovanillic acid (HVA) concentrations in the hippocampus and cortex that were associated with decreased cortical BDNF gene expression. In contrast, pro-inflammatory cytokine gene transcripts and serum IL-1α, IL-1β, TNF-α and IL-6 were unaffected by the short-term HFD feeding. Administration to mice of the psychostimulant methylphenidate prevented HFD-dependent impairment of learning/memory. HFD learning/memory impairment was not inhibited by the anti-depressants desipramine or reboxetine nor was it blocked in IDO or IL-1R1 knockout mice. In sum, a HFD rapidly impacts dopamine metabolism in the brain appearing to trigger anxiety-like behaviors and learning/memory impairments prior to the onset of weight gain and/or pre-diabetes. Thus, overnutrition due to fats may be central to childhood psychological perturbations such as anxiety and ADHD.

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“…We suspected differences in the used caging systems to be the cause for the observed heterogeneity. Indeed, a recent publication reveals that mice from individually ventilated cages (IVC) suffer from chronic low grade hypoxia as compared to ambient environment caging (AEC) (York et al 2012 ). In this work we show data, suggesting the used caging system as an important contributing factor to the observed ROS results.…”

Section: Introductionmentioning

confidence: 48%

“…As recently shown, mice from AEC conditions have normoxic blood parameters whereas animals from IVC systems suffer from chronic low grade hypoxia evidenced by corresponding blood parameters such as increased hematocrit, red blood cell count etc. (York et al 2012 ).…”

Section: Resultsmentioning

confidence: 95%

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Measurement of ROS Levels and Membrane Potential Dynamics in the Intact Carotid Body Ex Vivo

Bernardini

Brockmeier

Metzen

et al. 2015

Advances in Experimental Medicine and Biology

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Reactive oxygen species (ROS) generated by the NADPH oxidase have been proposed to play an important role in the carotid body (CB) oxygen sensing process (Cross et al. 1990). Up to now it remains unclear whether hypoxia causes an increase or decrease of CB ROS levels. We transfected CBs with the ROS sensitive HSP-FRET construct and subsequently measured the intracellular redox state by means of Förster resonance energy transfer (FRET) microscopy. In a previous study we found both increasing and decreasing ROS levels under hypoxic conditions. The transition from decreasing to increasing ROS levels coincided with the change of the caging system from ambient environment caging (AEC) to individually ventilated caging (IVC) (Bernardini A, Brockmeier U, Metzen E, Berchner-Pfannschmidt U, Harde E, Acker-Palmer A, Papkovsky D, Acker H, Fandrey J, Type I cell ROS kinetics under hypoxia in the intact mouse carotid body ex vivo: a FRET based study. Am J Physiol Cell Physiol. doi: 10.1152/ajpcell.00370.2013 , 2014). In this work we analyze hypoxia induced ROS reaction of animals from an IVC system that had been exposed to AEC conditions for 5 days. The results further support the hypothesis of an important impact of the caging system on CB ROS reaction.

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Individually ventilated cages cause chronic low-grade hypoxia impacting mice hematologically and behaviorally

Cited by 26 publications

References 48 publications

Mouse Short- and Long-term Locomotor Activity Analyzed by Video Tracking Software

Mouse Short- and Long-term Locomotor Activity Analyzed by Video Tracking Software

Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice

Measurement of ROS Levels and Membrane Potential Dynamics in the Intact Carotid Body Ex Vivo

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