Environmental bias? Effects of housing conditions, laboratory environment and experimenter on behavioral tests

Lewejohann, Lars; Reinhard, Christian; Schrewe, A.; Brandewiede, Joerg; Haemisch, Andreas; Görtz, Nicole; Schachner, Melitta; Sachser, Norbert

doi:10.1111/j.1601-183x.2005.00140.x

Cited by 118 publications

(95 citation statements)

References 26 publications

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“…In contrast, no deficits were observed by Salinger et al in a floorplate nose-poke task (Salinger et al 2003). These inconsistencies between laboratories may result from differences in the age of the mice, training and testing protocols, rearing conditions, and genetic background, all of which can easily influence the outcome of behavioral experiments (Wahlsten et al 2003;Lewejohann et al 2006). This potential susceptibility to precise experimental conditions may reflect the fact that changes induced by reelin haploinsufficiency are either very specific or very subtle.…”

Section: Discussionmentioning

confidence: 98%

Assessment of cognitive function in the heterozygous reeler mouse

et al. 2006

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RATIONALE-The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia, based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal cortex-dependent cognitive function, has yet to be determined.OBJECTIVE-Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients.METHODS-Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task; (2) impulsivity in an inhibitory control task; (3) attentional function in a threechoice serial reaction time task; and (4) working memory in a delayed matching-to-position task.RESULTS-No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning.CONCLUSIONS-These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.

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Section: Discussionmentioning

confidence: 98%

Assessment of cognitive function in the heterozygous reeler mouse

et al. 2006

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“…The ndings of this paper have important implications for animal husbandry and housing standardization. Behavioral testing across laboratories does not always yield similar results despite rigorous attempts at standardization [46,47]. One unknown variable that may contribute to be disparate behaviors across laboratories may be bedding.…”

Section: Discussionmentioning

confidence: 99%

Influence of housing variables on the development of stress-sensitive behaviors in the rat

Sakhai

Preslik

Francis

2013

Physiology & Behavior

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• Laboratory bedding material inuences developmental programming of rats.• Bedding material during early life can alter stress sensitive measures in adulthood.• Corncob bedding during sensitive periods decreases adult measures of anxiety.• Bedding material during adulthood does not affect adult anxiety-like behavior. Diverse environments early in mammalian life can have profound inuences on the physiology and behavior of developing offspring. Environmental factors can inuence offspring development directly or through perturbations in parental care. In the current study, we wished to determine if the inuence of a single environmental variable, type of bedding material used in laboratory cages, is capable of altering physiological and behavioral outcomes in offspring. Female rats were housed in cages containing wood pulp or corncob bedding and allowed to mature. These rats, while housed on assigned bedding material, were bred and allowed to give birth. At weaning, male offspring were housed on one of the two bedding conditions and tested later in adulthood on stress-sensitive behavioral measures. Postmortem analysis of glucocorticoid receptor expression and CRH mRNA levels were also measured. Maternal care directed at the pups reared in the two different bedding conditions was also recorded. Rats reared from birth on corncob bedding exhibited decreased anxiety-like behavior, as adults, in both open eld and light-dark box tasks compared to wood pulp reared animals. Animals that received similar overall levels of maternal care, regardless of bedding condition, also differed in anxiety-like behaviors as adults, indicating that the bedding condition is capable of altering phenotype independent of maternal care. Despite observed behavioral differences in adult offspring reared in different bedding conditions, no changes in glucocorticoid receptor expression at the level of the hippocampus, frontal cortex, or corticotrophin releasing hormone (CRH) mRNA expression in the hypothalamus were observed between groups. These results highlight the importance of early life housing variables in programming stress-sensitive behaviors in adult offspring. a b s t r a c t a r t i c l e i n f oPublished by Elsevier Inc.

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“…For a detailed description of behavioral tests see Ref. 29. Data analysis was conducted using the statistical software "R" (The R Project for Statistical Computing, available on the web) using non-parametric statistics.…”

Section: Figure 3 Ndst3mentioning

confidence: 99%

Altered Heparan Sulfate Structure in Mice with Deleted NDST3 Gene Function

Pallerla¹,

Lawrence

Lewejohann

et al. 2008

Journal of Biological Chemistry

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We report the generation and analysis of mutant mice bearing a targeted disruption of the heparan sulfate (HS)-modifying enzyme GlcNAc N-deacetylase/N-sulfotransferase 3 (NDST3). NDST3؊/؊ mice develop normally, are fertile, and show only subtle hematological and behavioral abnormalities in agreement with only moderate HS undersulfation. Compound mutant mice made deficient in NDST2;NDST3 activities also develop normally, showing that both isoforms are not essential for development. In contrast, NDST1؊/؊ ;NDST3 ؊/؊ compound mutant embryos display developmental defects caused by severe HS undersulfation, demonstrating NDST3 contribution to HS synthesis in the absence of NDST1. Moreover, analysis of HS composition in dissected NDST3 mutant adult brain revealed regional changes in HS sulfation, indicating restricted NDST3 activity on nascent HS in defined wild-type tissues. Taken together, we show that NDST3 function is not essential for development or adult homeostasis despite contributing to HS synthesis in a region-specific manner and that the loss of NDST3 function is compensated for by the other NDST isoforms to a varying degree. Heparan sulfate (HS)2 is produced by most mammalian cells as part of membrane and extracellular matrix proteoglycans (1). The chain grows by the copolymerization of GlcA␤1,4 and GlcNAc␣1,4 residues and undergoes modification by one or more of the four NDST isozymes, which remove acetyl groups from subsets of GlcNAc residues and add sulfate to the free amino groups. In vertebrates, ndst1 and ndst2 mRNA are expressed in all embryonic and adult tissues examined, whereas ndst3 and ndst4 transcripts are predominantly expressed during embryonic development and in the adult brain (2). Most subsequent modifications of the HS chain by O-sulfotransferases and a GlcA C5-epimerase depend on the presence of GlcNS residues, making the NDSTs largely responsible for the generation of sulfated ligand binding sites in HS (3-5). In vitro, NDST3 differs biochemically from the other NDST isoforms by possessing a high deacetylase activity but very low sulfotransferase activity (2).Many growth factors and morphogens bind to HS. In some cases, HS-proteoglycans are thought to act as co-receptors for these ligands. Studies in Drosophila melanogaster demonstrated that HS is crucial for embryonic development (6) and that the fly NDST ortholog, Sulfateless, affects signaling mediated by Wingless (Wg), Hedgehog (HH), and fibroblast growth factor (FGF) (7-9). The ability of HS to regulate the activity of morphogens and growth factors is currently best understood for the FGFs. HS was found to be a necessary component of FGF-FGF receptor binding and assembly (10), and global changes in HS expression regulate FGF and FGF receptor assembly during mouse development (11). Due to the multiple developmental processes regulated by the 23 FGFs, including those of the lung, limbs, heart, skeleton, and brain (reviewed in Ref. 12), perturbed HS synthesis results in the generation of FGF-related phenotypes (13,14). The crucial rol...

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Environmental bias? Effects of housing conditions, laboratory environment and experimenter on behavioral tests

Cited by 118 publications

References 26 publications

Assessment of cognitive function in the heterozygous reeler mouse

Assessment of cognitive function in the heterozygous reeler mouse

Influence of housing variables on the development of stress-sensitive behaviors in the rat

Altered Heparan Sulfate Structure in Mice with Deleted NDST3 Gene Function

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