Biology subjects

Anastassiadis, C.

Publications and source records attributed to Anastassiadis, C..

4 recordsLinked to original sources

bioRxiv2025

Examining Alzheimer's Disease Modifiable Risk Factors: Impact of Physical Activity and Diet on Neuroanatomy and Behaviour in Mice

Dementia is a global public health challenge, with obesity emerging as an important modifiable risk factor. Here, we examined whether lifestyle interventions can mitigate the effects of diet-induced obesity on body weight, behaviour, and brain anatomy in mouse models. Using a longitudinal design, wild-type and triple-transgenic (3xTgAD) mouse models of Alzheimers disease were exposed to a high-fat diet and assigned to one of three interventions: voluntary physical activity, a low-fat diet, and their combination. A high-fat diet significantly increased body weight and induced widespread neuroanatomical changes, with effects modulated by sex and genotype. The combined intervention led to significant weight loss in males of both genotypes. Neuroanatomical analyses revealed that a high-fat diet significantly reduced hippocampal and cerebellar volumes in wild-type mice but had a less pronounced effect on 3xTgAD mice; nevertheless, interventions, particularly the combined approach, increased localized brain volumes in these regions regardless of genotype. Multivariate integration of behavioural and neuroanatomical measures identified a brain pattern linking hippocampal and cerebellar volumes to intervention and behavioural performance. Spatial gene enrichment analysis of this pattern identified biological processes, including glucose homeostasis, as potential biological mechanisms underlying intervention effects. Overall, these findings suggest that voluntary physical activity and a low-fat diet can modulate brain structure and behaviour, partially counteracting the effects of a high-fat diet, and potentially recruiting biological processes that may support brain health.

neuroscience↗

bioRxiv2023

Effects of sex and gonadal hormones on manually segmented hypothalamic and pituitary gland volumes in young healthy adults

The hypothalamus and pituitary regulate, amongst other functions, third order endocrine systems, and their volumes have been associated with normal and pathological outcomes. Yet, there are very few studies that examine their combined structural variations in vivo. This is due, in part, to their small size and a lack of comprehensive image segmentation protocols. In the current project we acquired high-resolution T1- (1mm isotropic) and T2-weighted (0.4mm in plane resolution) 3T magnetic resonance images (MRI) of the hypothalamus and pituitary gland, as well as salivary estradiol and testosterone from 31 (17M, 14F) young healthy adults. Women reported oral contraceptive use. Image preprocessing included non-uniformity correction, signal intensity normalization and standard stereotaxic space registration. We applied a comprehensive manual segmentation protocol of the whole hypothalamus, with detailed segmentation of the pituitary stalk, the anterior and posterior pituitary gland, and the posterior bright spot. We also propose a novel medial-lateral hypothalamic parcellation into medial preoptic, periventricular (PVN), and lateral hypothalamic regions. The protocol yielded good inter- (range: 0.78-0.92) and intra-rater (range: 0.79-0.94) Dice kappa overlap coefficients. We detected sex differences of the whole hypothalamus and each hemisphere, and a trend for the right preoptic region to be larger in males than in females, with a moderate effect size. Sex differences were maintained or enhanced when covarying for estradiol, but not when covarying for testosterone. In addition, testosterone was associated with the volume of the PVN, but only in women. In summary, these results suggest that there are morphometric differences at the level of the pituitary and hypothalamus that are likely driven by central regulation of gonadal hormones. The here described protocol allows the structural investigation of neuroendocrine effects in the central nervous system.

neuroscience↗

bioRxiv2022

Examining Litter Specific Variability in Mice and its Impact on Neurodevelopmental Studies

Our current understanding of litter variability in neurodevelopmental studies using mouse may limit translation of neuroscientific findings. Higher variance of measures across litters than within, often termed intra-litter likeness, may be attributable to pre- and postnatal environment. This study aimed to assess the litter-effect within behavioral assessments (2 timepoints), and anatomy using T1-weighted magnetic resonance images (4 timepoints) across 72 brain region volumes (36 C57bl/6J inbred mice; 7 litters: 19F/17M). Between-litter comparisons of brain and behavioral measures and their associations were evaluated using univariate and multivariate techniques. A power analysis using simulation methods was then performed modeling neurodevelopment and evaluating trade-offs between number-of-litters, mice-per-litter, and sample size. Our results show litter-specific developmental effects, from the adolescent period to adulthood for brain structure volumes and behaviors, and their associations in adulthood. Our power simulation analysis results suggest increasing the number-of-litters in experimental design to achieve the smallest total sample size for detecting different rates of change in specific brain regions. Our results also demonstrate how litter-specific effects may influence development and that increasing the litters to the total sample size ratio should be strongly considered when designing neurodevelopmental studies.

neuroscience↗

bioRxiv2020

Early or late gestational exposure to maternal immune activation alters neurodevelopmental trajectories in mice: an integrated neuroimaging, behavioural, and transcriptional study

Prenatal maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders. How gestational timing of MIA-exposure differentially impacts downstream development remains unclear. Here, we characterize neurodevelopmental trajectories of mice exposed to MIA induced by poly I:C either early (gestational day [GD]9) or late (GD17) in gestation using longitudinal structural magnetic resonance imaging from weaning to adulthood. Early MIA-exposure associated with accelerated brain volume increases in adolescence/early-adulthood that normalized in later adulthood, in regions including the striatum, hippocampus, and cingulate cortex. Similarly, alterations in anxiety, stereotypic, and sensorimotor gating behaviours observed in adolescence normalized in adulthood. In contrast, MIA-exposure in late gestation had less impact on anatomical and behavioural profiles. Using a multivariate technique to relate imaging and behavioural variables for the time of greatest alteration, i.e. adolescence/early adulthood, we demonstrate that variation in anxiety, social, and sensorimotor gating associates significantly with volume of regions including the dorsal and ventral hippocampus, and anterior cingulate cortex. Using RNA sequencing to explore the molecular underpinnings of region-specific alterations in early MIA-exposed mice in adolescence, we observed the most transcriptional changes in the dorsal hippocampus, with regulated genes enriched for fibroblast growth factor regulation, autistic behaviours, inflammatory pathways, and microRNA regulation. This indicates that MIA in early gestation perturbs brain development mechanisms implicated in neurodevelopmental disorders. Our findings demonstrate the inherent strength of an integrated hypothesis- and data-driven approach in linking brain-behavioural alterations to the transcriptome to understand how MIA confers risk for major mental illness.

neuroscience↗