scholarly journals Comprehensive characterization of motor and coordination functions in three adolescent wild-type mouse strains

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ahmed Eltokhi ◽  
Barbara Kurpiers ◽  
Claudia Pitzer
Keyword(s):  
Developmental Stages ◽  
Wild Type Mouse ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Face Validity ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wild Type ◽  
Behavioral Experiments ◽  
Behavioral Studies

AbstractNeuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders. Although the onset of many neuropsychiatric disorders including autism spectrum disorder, schizophrenia, and attention-deficit hyperactivity disorder emerges mainly during infancy and adolescence, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, possibly missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we examined which behavioral tests assessing both motor and coordination functions can be performed in mice at two different adolescent stages. As strain and sex affect mouse behavior, our experiments covered both male and female mice of three inbred wild-type strains, C57BL/6N, DBA/2, and FVB/N. Adolescent mice of both postnatal days (P)22–30 and P32–40 developmental stages were capable of mastering common motor and coordination tests. However, results differed significantly between strains and sexes. Moreover, the 10-day interval between the two tested cohorts uncovered a strong difference in the behavioral results, confirming the significant impact of maturation on behavioral patterns. Interestingly, the results of distinct behavioral experiments were directly correlated with the weight of mice, which may explain the lack of reproducibility of some behavioral results in genetically-modified mice. Our study paves the way for better reproducibility of behavioral tests by addressing the effect of the developmental stage, strain, sex, and weight of mice on achieving the face validity of neuropsychiatric disorder-associated motor dysfunctions.

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

1995 ◽  
Vol 53 ◽  
pp. 970-971
Author(s):  
L. Vacca-Galloway ◽  
Y.Q. Zhang ◽  
P. Bose ◽  
S.H. Zhang
Keyword(s):  
Spinal Cord ◽  
Early Stage ◽  
Cervical Spinal Cord ◽  
Wild Type Mouse ◽  
Reflex Response ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wobbler Mouse ◽  
Stage 4 ◽  
Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

scholarly journals Transmission and Adaptation of Chronic Wasting Disease to Hamsters and Transgenic Mice: Evidence for Strains

2007 ◽  
Vol 81 (8) ◽  
pp. 4305-4314 ◽  
Author(s):  
Gregory J. Raymond ◽  
Lynne D. Raymond ◽  
Kimberly D. Meade-White ◽  
Andrew G. Hughson ◽  
Cynthia Favara ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Wild Type Mouse ◽  
Mouse Strains ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Wasting Disease ◽  
Incubation Periods

ABSTRACT In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

scholarly journals Which Zebrafish Strains Are More Suitable to Perform Behavioral Studies? A Comprehensive Comparison by Phenomic Approach

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 200 ◽  
Author(s):  
Gilbert Audira ◽  
Petrus Siregar ◽  
Stefan-Adrian Strungaru ◽  
Jong-Chin Huang ◽  
Chung-Der Hsiao
Keyword(s):  
Coefficient Of Variation ◽  
Predator Avoidance ◽  
Principal Component ◽  
Behavioral Tests ◽  
Wild Type ◽  
Behavioral Differences ◽  
Behavioral Test ◽  
Behavioral Studies ◽  
Comprehensive Comparison ◽  
Different Strains

Wild-type (WT) zebrafish are commonly used in behavioral tests, however, the term WT corresponds to many different strains, such as AB, Tübingen long fin (TL), and Wild Indian Karyotype (WIK). Since these strains are widely used, there has to be at least one study to demonstrate the behavioral differences between them. In our study, six zebrafish strains were used, which are AB, absolute, TL, golden, pet store-purchased (PET), and WIK zebrafishes. The behavior of these fishes was tested in a set of behavioral tests, including novel tank, mirror-biting, predator avoidance, social interaction, and shoaling tests. From the results, the differences were observed for all behavioral tests, and each strain displayed particular behavior depending on the tests. In addition, from the heatmap and PCA (principal component analysis) results, two major clusters were displayed, separating the AB and TL zebrafishes with other strains in another cluster. Furthermore, after the coefficient of variation of each strain in every behavioral test was calculated, the AB and TL zebrafishes were found to possess a low percentage of the coefficient of variation, highlighting the strong reproducibility and the robustness of the behaviors tested in both fishes. Each zebrafish strain tested in this experiment showed specifically different behaviors from each other, thus, strain-specific zebrafish behavior should be considered when designing experiments using zebrafish behavior.

scholarly journals Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish

2021 ◽  
Author(s):  
Ester Anton-Galindo ◽  
Elisa Dalla Vecchia ◽  
Javier G Orlandi ◽  
Gustavo Castro ◽  
Emilio Gualda ◽  
...  
Keyword(s):  
Neural Development ◽  
Neurodevelopmental Disorders ◽  
Genome Engineering ◽  
Developmental Stages ◽  
Brain Activity ◽  
Autism Spectrum ◽  
Wild Type ◽  
Zebrafish Model ◽  
Risk Variants

Genetic risk variants in YWHAZ, encoding 14-3-ζ, have been found to contribute to psychiatric disorders such as autism spectrum disorder and schizophrenia, and have been related to an impaired neurodevelopment in humans and mice. Here, we have used a zebrafish model to further understand the mechanisms by which YWHAZ contribute to neurodevelopmental disorders. We first observed pan-neuronal expression of ywhaz during developmental stages, suggesting an important role of this gene in neural development. During adulthood ywhaz expression was restricted to Purkinje cells in the cerebellum, a region that shows alterations in autistic patients. We then established a novel stable ywhaz knockout (KO) zebrafish line using CRISPR/Cas9 genome engineering. We performed whole-brain calcium imaging in wild-type (WT) and ywhaz KO larvae and found altered neural activity and functional connectivity in the hindbrain. Interestingly, adult ywhaz KO fish also display decreased levels of dopamine and serotonin in the hindbrain and freeze when exposed to novel stimuli, a phenotype that can be reversed with fluoxetine and quinpirole, drugs that target serotonin and dopamine neurotransmission. Together, these findings suggest an important role for ywhaz in establishing neuronal connectivity during developmental stages. ywhaz deficiency leads to impaired dopamine and serotonin neurotransmission that may underlie the altered behaviour observed during adulthood.

scholarly journals Gait performance of adolescent mice assessed by the CatWalk XT depends on age, strain and sex and correlates with speed and body weight

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Pitzer ◽  
Barbara Kurpiers ◽  
Ahmed Eltokhi
Keyword(s):  
Body Weight ◽  
Gait Analysis ◽  
Inbred Mouse ◽  
Neuropsychiatric Disorders ◽  
Face Validity ◽  
Mouse Strains ◽  
Rodent Models ◽  
Gait Performance ◽  
Sex Development ◽  
Gait Abnormalities

AbstractThe automatization of behavioral tests assessing motor activity in rodent models is important for providing robust and reproducible results and evaluating new therapeutics. The CatWalk system is an observer-independent, automated and computerized technique for the assessment of gait performance in rodents. This method has previously been used in adult rodent models of CNS-based movement disorders such as Parkinson’s and Huntington’s diseases. As motor and gait abnormalities in neuropsychiatric disorders are observed during infancy and adolescence, it became important to validate the CatWalk XT in the gait analysis of adolescent mice and unravel factors that may cause variations in gait performance. Three adolescent wild-type inbred mouse strains, C57BL/6N, DBA/2 and FVB/N, were tested using the CatWalk XT (Version 10.6) for suitable detection settings to characterize several gait parameters at P32 and P42. The same detection settings being suitable for C57BL/6N and DBA/2 mice allowed a direct comparison between the two strains. On the other hand, due to their increased body weight and size, FVB/N mice required different detection settings. The CatWalk XT reliably measured the temporal, spatial, and interlimb coordination parameters in the investigated strains during adolescence. Additionally, significant effects of sex, development, speed and body weight within each strain confirmed the sensitivity of motor and gait functions to these factors. The CatWalk gait analysis of rodents during adolescence, taking the effect of age, strain, sex, speed and body weight into consideration, will decrease intra-laboratory discrepancies and increase the face validity of rodent models of neuropsychiatric disorders.

scholarly journals Baseline Depression-Like Behaviors in Wild-Type Adolescent Mice Are Strain and Age but Not Sex Dependent

2021 ◽  
Vol 15 ◽  
Author(s):  
Ahmed Eltokhi ◽  
Barbara Kurpiers ◽  
Claudia Pitzer
Keyword(s):  
Sex Differences ◽  
Mouse Models ◽  
Public Health Problem ◽  
Neuropsychiatric Disorders ◽  
Sensitive Period ◽  
Strong Impact ◽  
Rodent Models ◽  
Wild Type ◽  
Behavioral Experiments ◽  
Behavioral Outcome

Depression is a major neuropsychiatric disorder, decreasing the ability of hundreds of millions of individuals worldwide to function in social, academic, and employment settings. Beyond the alarming public health problem, depression leads to morbidity across the entire age including adolescence and adulthood. Modeling depression in rodents has been used to understand the pathophysiological mechanisms behind this disorder and create new therapeutics. Although women are two times more likely to be diagnosed with depression compared to men, behavioral experiments on rodent models of depression are mainly performed in males based on the assumption that the estrous cycles in females may affect the behavioral outcome and cause an increase in the intrinsic variability compared to males. Still, the inclusion of female rodents in the behavioral analysis is mandatory to establish the origin of sex bias in depression. Here, we investigated the baseline depression-like behaviors in male and female mice of three adolescent wild-type inbred strains, C57BL/6N, DBA/2, and FVB/N, that are typically used as background strains for mouse models of neuropsychiatric disorders. Our experiments, performed at two different developmental stages during adolescence (P22–P26 and P32–P36), revealed strain but no sex differences in a set of depression-related tests, including tail suspension, sucrose preference and forced swim tests. Additionally, the 10-day interval during this sensitive period uncovered a strong impact on the behavioral outcome of C57BL/6N and FVB/N mice, highlighting a significant effect of maturation on behavioral patterns. Since anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders, we extended our study and included hyponeophagia as an anxiety test. Consistent with a previous study revealing sex differences in other anxiety tests in adolescent mice, male and females mice behaved differently in the hyponeophagia test at P27. Our study gives insight into the behavioral experiments assessing depression and stresses the importance of considering strain, age and sex when evaluating neuropsychiatric-like traits in rodent models.

scholarly journals Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

2021 ◽  
Author(s):  
Nevena V. Radonjić ◽  
Jonathan L. Hess ◽  
Paula Rovira ◽  
Ole Andreassen ◽  
Jan K. Buitelaar ◽  
...  
Keyword(s):  
Association Studies ◽  
Genetic Correlations ◽  
Neuropsychiatric Disorders ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Genetic Etiology ◽  
Compulsive Disorder ◽  
Pairwise Correlations ◽  
Genomewide Association ◽  
Structural Brain

AbstractGenomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

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