Dataset Information

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation.

ABSTRACT: Early-life stress and its possible correlations to genes, environment, and later health outcomes can only be studied retrospectively in humans. Animal models enable the exploration of such connections with prospective, well-controlled study designs. However, with the recent awareness of replicability issues in preclinical research, the reproducibility of results from animal models has been highlighted. The present study aims to reproduce the behavioral effects of maternal separation (MS) previously observed in the multivariate concentric square fieldTM (MCSF) test. A second objective was to replicate the adolescent behavioral profiles previously described in the MCSF test. Male rats, subjected to short or prolonged MS or standard rearing, were subjected to behavioral testing in early adolescence and early adulthood. As seen in previous studies, the behavioral effects of MS in the MCSF were small at both tested time points. When tested in early adolescence, the animals exhibited a similar behavioral profile as previously seen, and the finding of adolescent behavioral types was also reproduced. The distribution of animals into the behavioral types was different than in the initial study, but in a manner consistent with developmental theories, as the current cohort was younger than the previous. Notably, the Shelter seeker behavioral type persisted through development, while the Explorer type did not. The lack of basal behavioral effect after MS is in line with the literature on this MS paradigm; the working hypothesis is that the prolonged MS gives rise to a phenotype predisposed to negative health outcomes but which is not apparent without additional provocation.

SUBMITTER: Lundberg S

PROVIDER: S-EPMC7096550 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation.

Lundberg Stina S Nylander Ingrid I Roman Erika E

Frontiers in behavioral neuroscience 20200319

Early-life stress and its possible correlations to genes, environment, and later health outcomes can only be studied retrospectively in humans. Animal models enable the exploration of such connections with prospective, well-controlled study designs. However, with the recent awareness of replicability issues in preclinical research, the reproducibility of results from animal models has been highlighted. The present study aims to reproduce the behavioral effects of maternal separation (MS) previou ...[more]

PMID: 32265671

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Project description:Early life stress (ELS) leads to a permanent reprogramming of biochemical stress response cascades that may also be relevant for the processing of chronic pain states such as neuropathy. Despite clinical evidence, little is known about ELS-related vulnerability for neuropathic pain and the possibly underlying etiology. In the framework of experimental studies aimed at investigating the respective relationships we used the established ELS model of maternal separation (MS). Rat dams and neonates were separated for 3 h/day from post-natal day 2-12. At adulthood, noxious mechanical and thermal thresholds were assessed before and during induction of neuropathic pain by chronic constriction injury (CCI). The potential involvement of spinal glutamatergic transmission, glial cells, pro-inflammatory cytokines and growth factors was studied by using qPCR. MS per se did not modify pain thresholds. But, when exposed to neuropathic pain, MS rats exhibited a marked reduction of thermal sensitivity and a delayed development of mechanical allodynia/hyperalgesia when compared to control animals. Also, MS did not alter glucocorticoid receptor mRNA levels, but prevented the CCI-induced down-regulation of NR1 and NR2 sub-units of the NMDA receptor and of the glutamate transporter EAAT3 as observed at 21 days post-surgery. Additionally, CCI-provoked up-regulation of glial cell markers was either prevented (GFAP for astrocytes) or dampened (Iba1 for microglia) by MS. Pro-inflammatory cytokine mRNA expression was either not affected (IL-6) or reduced (IL-1?) by MS shortly after CCI. The growth factors GDNF and NGF were only slightly downregulated 4 days after CCI in the MS-treated animals. The changes in glutamatergic signaling, astroglial and cytokine activation as well as neurotrophin expression could, to some extent, explain these changes in pain behavior. Taken together, the results obtained in the described experimental conditions support the mismatch theory of chronic stress where an early life stress, rather than predisposing individuals to certain pathologies, renders them resilient.

Project description:BackgroundAs more adults undergo surgical fixation of clavicle fractures with improved outcomes, interest is renewed in managing clavicle fractures in adolescents. The medial clavicular physis does not fuse until 23 to 25 years of age, but studies report minimal clavicular growth during adolescence-studies that employed cross-sectional methodologies, which cannot not capture growth in patients over time. The assumption that clavicle length at each stage is uniform, as is the final overall length, may not be accurate if the age groups studied comprise various ethnicities, socioeconomic status, or height.Questions/purposesWe sought to quantify longitudinal clavicular growth on serial radiographs in adolescents and young adults. Our hypothesis was that substantial clavicular growth would be seen beyond the age of 12 years.MethodsWe conducted a longitudinal case series of non-syndromic patients in a single orthopedic clinic and analyzed serial radiographic images of the clavicles. For ethical reasons, only patients with non-neuromuscular scoliosis and kyphosis (in whom the existing standard of care includes serial thoracic radiographs) were considered for inclusion. Patients ages 10 to 25 years old were included in the study if three or more serial thoracic radiographs over a minimum 5 years were available that captured the entire length of at least one non-rotated clavicle. Three types of radiographs were included for analysis: digital low-dose-radiation stereoradiographic (EOS Imaging, Paris, France), non-EOS digital, and non-EOS printed. The overall longitudinal growth, yearly growth, and the yearly growth percentage were calculated for each clavicle.ResultsFifty-seven patients (22 male and 35 female) met the inclusion criteria. In male patients, at ages 12 to 15 years, the clavicular growth was 4.9 mm/year, or 4%/year; at ages 16 to 19 years, growth was 3.2 mm/year, or 2.4%/year; and at ages 20 to 25 years, growth was 1.7 mm/year, or 1.1%/year. In female patients, at ages 12 to 15 years, growth was 4.7 mm/year, or 4%/year; at 16 to 19 years, growth was 2.2 mm/year, or 1.7%/year; and at ages 20 to 25 years, growth was 0.2 mm/year or 0.1%/year. We could not detect the age of terminal growth in either sex because growth was ongoing in most patients in the oldest group.ConclusionWe found substantial clavicular growth potential after age 18 years, when growth is thought to be nearly finished, as well as remodeling potential even up to age 25 years. Further research is needed, but our findings suggest that strategies for managing clavicle fracture in adults may not be applied universally to adolescents and young adults.

Dataset Information

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation.

Publications

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation.

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