Dataset Information

Altered Behavior in Mice Socially Isolated During Adolescence Corresponds With Immature Dendritic Spine Morphology and Impaired Plasticity in the Prefrontal Cortex.

ABSTRACT: Mice socially isolated during adolescence exhibit behaviors of anxiety, depression and impaired social interaction. Although these behaviors are well documented, very little is known about the associated neurobiological changes that accompany these behaviors. It has been hypothesized that social isolation during adolescence alters the development of the prefrontal cortex, based on similar behavioral abnormalities observed in isolated mice and those with disruption of this structure. To establish relationships between behavior and underlying neurobiological changes in the prefrontal cortex, Thy-1-GFP mice were isolated from weaning until adulthood and compared to group-housed littermates regarding behavior, electrophysiological activity and dendritic morphology. Results indicate an immaturity of dendritic spines in single housed animals, with dendritic spines appearing smaller and thinner. Single housed mice additionally show impaired plasticity through measures of long-term potentiation. Together these findings suggest an altered development and impairment of the prefrontal cortex of these animals underlying their behavioral characteristics.

SUBMITTER: Medendorp WE

PROVIDER: S-EPMC5954042 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Altered Behavior in Mice Socially Isolated During Adolescence Corresponds With Immature Dendritic Spine Morphology and Impaired Plasticity in the Prefrontal Cortex.

Medendorp William E WE Petersen Eric D ED Pal Akash A Wagner Lina-Marie LM Myers Alexzander R AR Hochgeschwender Ute U Jenrow Kenneth A KA

Frontiers in behavioral neuroscience 20180509

Mice socially isolated during adolescence exhibit behaviors of anxiety, depression and impaired social interaction. Although these behaviors are well documented, very little is known about the associated neurobiological changes that accompany these behaviors. It has been hypothesized that social isolation during adolescence alters the development of the prefrontal cortex, based on similar behavioral abnormalities observed in isolated mice and those with disruption of this structure. To establish ...[more]

PMID: 29867388

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Project description:Prior studies have demonstrated reduced dendritic spine density in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. However, it remains unclear how generalizable this finding is in schizophrenia and if it is seen in bipolar disorder, a historically distinct psychiatric condition.To assess whether spine loss is present in the DLPFC of individuals with schizophrenia and individuals with bipolar disorder.This study used postmortem human brain tissue from individuals with schizophrenia (n=14), individuals with bipolar disorder (n=9), and unaffected control participants (n=19). Tissue samples containing the DLPFC (Brodmann area 46) were Golgi-stained, and basilar dendrites of pyramidal cells in the deep half of layer III were reconstructed.The number of spines per dendrite, spine density, and dendrite length were compared across groups. We also assessed for the potential effects of clinical and demographic variables on dendritic parameters.The mean (SD) spine density was significantly reduced (ie, by 10.5%) in individuals with bipolar disorder (0.28 [0.04] spines/?m) compared with control participants (0.31 [0.05] spines/?m) (P=.02). In individuals with schizophrenia, the mean (SD) spine density was also reduced (by 6.5%; 0.29 [0.03] spines/?m) but just missed significance when compared with control participants (P=.06). There was a significant reduction in the mean (SD) number of spines per dendrite in both individuals with schizophrenia (72.8 [24.9] spines per dendrite) and individuals with bipolar disorder (68.9 [12.9] spines per dendrite) compared with controls (92.8 [31.1] spines per dendrite) (individuals with schizophrenia vs controls: 21.6% reduction [P=.003]; individuals with bipolar disorder vs controls: 25.8% reduction [P=.005]). In addition, both individuals with schizophrenia and individuals with bipolar disorder had a reduced mean (SD) dendrite length (246.5 [67.4] and 245.6 [29.8] ?m, respectively) compared with controls (301.8 [75.1] ?m) (individuals with schizophrenia vs controls: 18.3% reduction [P=.005]; individuals with bipolar disorder vs controls: 18.6% reduction [P=.005]).Dendritic spine loss in the DLPFC was seen in both individuals with schizophrenia and individuals with bipolar disorder, suggesting that the 2 disorders may share some common pathophysiological features.

Project description:Background: Neighborhood deprivation adversely effects neurodevelopment and cognitive function; however, mechanisms remain unexplored. Neighborhood deprivation could be particularly impactful in late childhood/early adolescence, in neural regions with protracted developmental trajectories, e.g., prefrontal cortex (PFC).Methods: The Adolescent Brain Cognitive Development (ABCD) study recruited 10,205 youth. Geocoded residential history was used to extract individual neighborhood characteristics. A general cognitive ability index and MRI scans were completed. Associations with neurocognition were examined. The relation of PFC surface area and cortical thickness to neighborhood deprivation was tested. PFC subregions and asymmetry, with putative differential environmental susceptibility during key developmental periods, were explored. Analyses tested PFC area as a possible mediating mechanism.Results: Neighborhood deprivation predicted neurocognitive performance (? ?= ?-0.11), even after accounting for parental education and household income (? ?= ?-0.07). Higher neighborhood deprivation related to greater overall PFC surface area (?p2 ?= ?0.003), and differences in leftward asymmetry were observed for area (?p2 ?= ?0.001), and thickness (?p2 ?= ?0.003). Subregion analyses highlighted differences among critical areas that are actively developing in late childhood/early adolescence and are essential to modulating high order cognitive function. These included orbitofrontal, superior frontal, rostral middle frontal, and frontal pole regions (Cohen's d ?= ?0.03-0.09). PFC surface area partially mediated the relation between neighborhood deprivation and neurocognition.Discussion: Neighborhood deprivation related to cognitive function (a foundational skill tied to a range of lifetime outcomes) and PFC morphology, with evidence found for partial mediation of PFC on neurocognitive function. Results inform public health conceptualizations of development and environmental vulnerability.

Dataset Information

Altered Behavior in Mice Socially Isolated During Adolescence Corresponds With Immature Dendritic Spine Morphology and Impaired Plasticity in the Prefrontal Cortex.

Publications

Altered Behavior in Mice Socially Isolated During Adolescence Corresponds With Immature Dendritic Spine Morphology and Impaired Plasticity in the Prefrontal Cortex.

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