Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is broadly characterized by neurodegeneration, pathology accumulation, and cognitive decline. There is considerable variation in the progression of clinical symptoms and pathology in humans, highlighting the importance of genetic diversity in the study of AD. To address this, we analyze cell composition and amyloid-beta deposition of 6- and 14-month-old AD-BXD mouse brains. We utilize the analytical QUINT workflow- a suite of software designed to support atlas-based quantification, which we expand to deliver a highly effective method for registering and quantifying cell and pathology changes in diverse disease models. In applying the expanded QUINT workflow, we quantify near-global age-related increases in microglia, astrocytes, and amyloid-beta, and we identify strain-specific regional variation in neuron load. To understand how individual differences in cell composition affect the interpretation of bulk gene expression in AD, we combine hippocampal immunohistochemistry analyses with bulk RNA-sequencing data. This approach allows us to categorize genes whose expression changes in response to AD in a cell and/or pathology load-dependent manner. Ultimately, our study demonstrates the use of the QUINT workflow to standardize the quantification of immunohistochemistry data in diverse mice, - providing valuable insights into regional variation in cellular load and amyloid deposition in the AD-BXD model.

Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is characterized by neurodegeneration, pathology accumulation, and progressive cognitive decline. There is significant variation in age at onset and severity of symptoms highlighting the importance of genetic diversity in the study of AD. To address this, we analyzed cell and pathology composition of 6- and 14-month-old AD-BXD mouse brains using the semi-automated workflow (QUINT); which we expanded to allow for nonlinear refinement of brain atlas-registration, and quality control assessment of atlas-registration and brain section integrity. Near global age-related increases in microglia, astrocyte, and amyloid-beta accumulation were measured, while regional variation in neuron load existed among strains. Furthermore, hippocampal immunohistochemistry analyses were combined with bulk RNA-sequencing results to demonstrate the relationship between cell composition and gene expression. Overall, the additional functionality of the QUINT workflow delivers a highly effective method for registering and quantifying cell and pathology changes in diverse disease models.

A cross-sectional matched sample study of nonsuicidal self-injury among young adults: support for interpersonal and intrapersonal factors, with implications for coping strategies.

BACKGROUND: Young adults are a high-risk group for nonsuicidal self-injury (NSSI). It is important to have a better understanding of these behaviors in order to facilitate effective research, intervention, and treatment. Models have been presented to explain these behaviors where emotion regulation, coping, and support play a role. Yet conflicting results have occurred based on demographic factors such as race and sex. While controlling for the observable demographic factors, this study sought to examine differences between individuals who currently engage in NSSI, engaged in NSSI in the past, and never engaged in NSSI related to emotions, coping strategies, interpersonal support, and ethnic identity and belonging. METHODS: Participants were selected from freshman students at two universities, in geographically different locations in the United States (N = 282). Participants in this study were matched on demographic factors: race, sex, and university. This led to demographically matched groups (current, past, never engagement in NSSI; n = 94 per group). Groups were compared on intrapersonal factors (i.e., emotions: depression and anxiety; coping strategies: adaptive and maladaptive; interpersonal support: family, friend, and significant other; and ethnic identity and belonging). Descriptive statistics and ANOVA with post hoc Scheffe were utilized to explicate differences between groups. RESULTS: Individuals who never engaged in NSSI reported significantly higher levels of ethnic belonging and interpersonal support and lower levels of depression and anxiety than both groups who engaged in NSSI. Individuals who never self-injured used less adaptive and maladaptive coping strategies than participants who self-injured. Young adults who currently engaged in NSSI reported higher levels of depression and anxiety, higher levels of both types of coping, and perceived less support. CONCLUSIONS: It is important to understand the differences between individuals who self-injure in comparison to those who do not so that mental health clinicians can provide more effective services and preventative efforts.