Biology subjects

Madularu, D.

Publications and source records attributed to Madularu, D..

3 recordsLinked to original sources

bioRxiv2021

Longitudinal characterization of neuroanatomical changes in the Fischer 344 rat brain during normal aging and between sexes

Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is also one of the most frequently used models in aging research. Despite frequency of use, characterization of neuroanatomical change with age has not been performed in the F344 rat. To this end, we present a comprehensive longitudinal examination of morphometric change in 73 brain regions and at a voxel-wise level during normative aging in a mixed-sex cohort of F344 rats. We identified age- and sex-related changes in regions such as the cortex, hippocampus, cingulum, caudoputamen, and nucleus accumbens, which are implicated in memory and motor control circuits frequently affected by aging and neurodegenerative disease. These findings provide a baseline for neuroanatomical changes associated with aging in male and female F344 rats, to which data from transgenic models or other background strains can be compared. HIGHLIGHTSO_LIIn vivo magnetic resonance imaging reveals altered neuroanatomy in aging Fischer rats C_LIO_LILinear and curvilinear age effects exist in both grey and white matter structures C_LIO_LISex differences are primarily seen in grey matter structures C_LIO_LIThis study clarifies normal aging trajectories across 73 brain regions in both sexes C_LIO_LIImproved understanding of normal aging will inform future pathological aging studies C_LI

neuroscience↗

bioRxiv2020

Longitudinal Quantification of Metabolites and Macromolecules Reveals Age- and Sex-Related Changes in the Healthy Fischer 344 Rat Brain

Normal aging is associated with numerous biological changes including altered brain metabolism and tissue chemistry. In vivo characterization of the neurochemical profile during aging is possible using magnetic resonance spectroscopy, a powerful non-invasive technique capable of quantifying brain metabolites involved in physiological processes that become impaired with age. A prominent macromolecular signal underlies those of brain metabolites and is particularly visible at high fields; parameterization of this signal into components improves quantification and expands the number of biomarkers comprising the neurochemical profile. The present study reports, for the first time, the simultaneous absolute quantification of brain metabolites and individual macromolecules in aging male and female Fischer 344 rats, measured longitudinally using proton magnetic resonance spectroscopy at 7T. We identified age- and sex-related changes in neurochemistry, with prominent differences in metabolites implicated in anaerobic energy metabolism, antioxidant capacity, and neuroprotection, as well as numerous macromolecule changes. These findings contribute to our understanding of the neurobiological processes associated with healthy aging, critical for the proper identification and management of pathological aging trajectories. HIGHLIGHTS[->] Magnetic resonance spectroscopy reveals altered chemistry in the aging rat brain [->]Age- and sex-dependent differences in metabolites and macromolecules are present [->]Metabolites and macromolecules are markers of processes involved in healthy aging [->]This study clarifies normative progression of brain chemistry and metabolism in vivo [->]Improved understanding will inform future studies in pathological aging

neuroscience↗

bioRxiv2019

An MRI-Derived Neuroanatomical Atlas of the Fischer 344 Rat Brain for Automated Anatomical Segmentation

This paper reports the development of a high-resolution 3-D MRI atlas of the Fischer 344 adult rat brain. The atlas is a 60 m isotropic image volume composed of 256 coronal slices with 71 manually delineated structures and substructures. The atlas was developed using Pydpiper image registration pipeline to create an average brain image of 41 four-month-old male and female Fischer 344 rats. Slices in the average brain image were then manually segmented, individually and bilaterally, on the basis of image contrast in conjunction with Paxinos and Watsons (2007) stereotaxic rat brain atlas. Summary statistics (mean and standard deviation of regional volumes) are reported for each brain region across the sample used to generate the atlas, and a statistical comparison of a chosen subset of regional brain volumes between male and female rats is presented. On average, the coefficient of variation of regional brain volumes across all rats in our sample was 4%, with no individual brain region having a coefficient of variation greater than 13%. A full description of methods used, as well as the atlas, the template that the atlas was derived from, and a masking file, can be found at Zenodo at https://doi.org/10.5281/zenodo.3555556. To our knowledge, this is the first MRI atlas created using Fischer 344 rats and will thus provide an appropriate neuroanatomical model for researchers working with this strain. HIGHLIGHTS Open-access high-resolution anatomical MRI template for Fischer 344 rat brain. Segmented atlas of 71 regions for use as a tool in Fischer 344 preclinical research paradigms. Analysis of population variability of regional brain volumes. Analysis of sex-differences in regional brain volumes KEYWORDS: Fischer 344; Structural MRI; Segmentation; Rat brain template; Digital brain atlas; Sex-differences;

neuroscience↗