Rodents, particularly mice and rats, are extensively utilized in fundamental neuroscience research. Brain atlases have played a pivotal role in this field, evolving from traditional printed histology atlases to digital atlases incorporating diverse imaging datasets. Magnetic resonance imaging (MRI)-based brain atlases, also known as brain maps, have been employed in specific studies. However, the existence of numerous versions of MRI-based brain atlases has impeded their standardized application and widespread use, despite the consensus within the academic community regarding their significance in mice and rats. Furthermore, there is a dearth of comprehensive and systematic reviews on MRI-based brain atlases for rodents. This review aims to bridge this gap by providing a comprehensive overview of the advancements in MRI-based brain atlases for rodents, with a specific focus on mice and rats. It seeks to explore the advantages and disadvantages of histologically printed brain atlases in comparison to MRI brain atlases, delineate the standardized methods for creating MRI brain atlases, and summarize their primary applications in neuroscience research. Additionally, this review aims to assist researchers in selecting appropriate versions of MRI brain atlases for their studies or refining existing MRI brain atlas resources, thereby facilitating the development and widespread adoption of standardized MRI-based brain atlases in rodents.

UNASSIGNED: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord with a poor prognosis. Previous studies have observed cognitive decline and changes in brain morphometry in ALS patients. However, it remains unclear whether the brain structural alterations contribute to the risk of ALS. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) and colocalization analysis to investigate this causal relationship.
UNASSIGNED: Summary data of genome-wide association study were obtained for ALS and the brain structures, including surface area (SA), thickness and volume of subcortical structures. Inverse-variance weighted (IVW) method was used as the main estimate approach. Sensitivity analysis was conducted detect heterogeneity and pleiotropy. Colocalization analysis was performed to calculate the posterior probability of causal variation and identify the common genes.
UNASSIGNED: In the forward MR analysis, we found positive associations between the SA in four cortical regions (lingual, parahippocampal, pericalcarine, and middle temporal) and the risk of ALS. Additionally, decreased thickness in nine cortical regions (caudal anterior cingulate, frontal pole, fusiform, inferior temporal, lateral occipital, lateral orbitofrontal, pars orbitalis, pars triangularis, and pericalcarine) was significantly associated with a higher risk of ALS. In the reverse MR analysis, genetically predicted ALS was associated with reduced thickness in the bankssts and increased thickness in the caudal middle frontal, inferior parietal, medial orbitofrontal, and superior temporal regions. Colocalization analysis revealed the presence of shared causal variants between the two traits.
UNASSIGNED: Our results suggest that altered brain morphometry in individuals with high ALS risk may be genetically mediated. The causal associations of widespread multifocal extra-motor atrophy in frontal and temporal lobes with ALS risk support the notion of a continuum between ALS and frontotemporal dementia. These findings enhance our understanding of the cortical structural patterns in ALS and shed light on potentially viable therapeutic targets.

BACKGROUND: The aim of this study was to develop a pipeline using state-of-the-art deep learning methods to automatically delineate and measure several of the most important brain structures in fetal brain ultrasound (US) images.
METHODS: The dataset was composed of 5,331 images of the fetal brain acquired during the routine mid-trimester US scan. Our proposed pipeline automatically performs the following three steps: brain plane classification (transventricular, transthalamic, or transcerebellar plane); brain structures delineation (9 different structures); and automatic measurement (from the structure delineations). The methods were trained on a subset of 4,331 images and each step was evaluated on the remaining 1,000 images.
RESULTS: Plane classification reached 98.6% average class accuracy. Brain structure delineation obtained an average pixel accuracy higher than 96% and a Jaccard index higher than 70%. Automatic measurements get an absolute error below 3.5% for the four standard head biometries (head circumference, biparietal diameter, occipitofrontal diameter, and cephalic index), 9% for transcerebellar diameter, 12% for cavum septi pellucidi ratio, and 26% for Sylvian fissure operculization degree.
CONCLUSIONS: The proposed pipeline shows the potential of deep learning methods to delineate fetal head and brain structures and obtain automatic measures of each anatomical standard plane acquired during routine fetal US examination.

UNASSIGNED: TV viewing in the elderly and in children is associated with subsequent greater decline of various cognitive functions including verbal working memory, but results of its association with subsequent risk of dementia were divided.
UNASSIGNED: In this longitudinal cohort study of UK Biobank, we investigated the associations of TV viewing length with subsequent risk of dementia and longitudinal changes of brain structural measures after corrections of a wide range of potential confounders.
UNASSIGNED: Our results showed longer TV viewing was associated with increased risk of subsequent onset of dementia, as well as subsequent greater decline in intracellular volume fraction (ICVF) in the extensive areas of right lateral temporal cortex and the right medial temporal cortex, in the area around the left middle and inferior temporal cortex as well as the left fusiform gyrus, and the area adjacent to the left inferior frontal gyrus, and left insula.
UNASSIGNED: These results may suggest prolonged TV viewing was associated with decline in density of neurites (axon, dendrites) in areas particularly implicated in language, communication, and memory, which are altered in dementia.

Social isolation (SI) is chronic psycho-emotional stress for humans and other socially living species. There are few comparative studies that have measured monoamine levels in brain structures in male and female rats subjected to SI. Existing data is highly controversial. In our recent study, we investigated behavioral effects of SI prolonged up to 9 months on a rather large sample of 69 male and female Wistar rats. In the present study, we measured the levels of monoamines-norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), and DA and 5-HT metabolites-in the brain structures of 40 rats from the same sample. The single-housed rats of both sexes showed hyperactivity and reduced reactivity to novelty in the Open Field test, and impaired passive avoidance learning. Regardless of their sex, by the time of sacrifice, the single-housed rats weighed less and had lower pain sensitivity and decreased anxiety compared with group-housed animals. SI decreased NE levels in the hippocampus and increased them in the striatum. SI induced functional activation of the DA-ergic system in the frontal cortex and hypothalamus, with increased DA and 3-methoxytyramine levels. SI-related changes were found in the 5-HT-ergic system: 5-HT levels increased in the frontal cortex and striatum, while 5-hydroxyindoleacetic acid only increased in the frontal cortex. We believe that SI prolonged for multiple months could be a valuable model for comparative analysis of the behavioral alterations and the underlying molecular processes in dynamics of adaptation to chronic psychosocial stress in male and female rats in relation to age-dependent changes.

Anxiety disorders are one of the most prevalent mood disorders that can lead to impaired quality of life. Current treatment of anxiety disorders has various adverse effects, safety concerns, or restricted efficacy; therefore, novel therapeutic targets need to be studied. Sex steroid hormones (SSHs) play a crucial role in the formation of brain structures, including regions of the limbic system and prefrontal cortex during perinatal development. In the brain, SSHs have activational and organizational effects mediated by either intracellular or transmembrane G-protein coupled receptors. During perinatal developmental periods, the physiological concentrations of SSHs lead to the normal development of the brain; however, the early hormonal dysregulation could result in various anxiety diorders later in life. Sex differences in the prevalence of anxiety disorders suggest that SSHs might be implicated in their development. In this review, we discuss preclinical and clinical studies regarding the role of dysregulated SSHs signaling during early brain development that modifies the risk for anxiety disorders in a sex-specific manner in adulthood. Moreover, our aim is to summarize potential molecular mechanisms by which the SSHs may affect anxiety disorders in preclinical research. Finally, the potential effects of SSHs in the treatment of anxiety disorders are discussed.

The relationship between obesity and neurocognitive consequences is complex. Here we investigated associations between body mass index (BMI) and subsequent changes in brain structures, cognitive changes, and the onset of dementia after adjustment of a wide range of potential confounding variables using a large prospective cohort data of UK Biobank. After correcting for confounding factors, higher BMI was associated with greater retention in visuospatial memory performance (decline in error numbers) [beta = -0.019 (CI:-0.027~-0.016), N = 39191], increase in depression tendency scores [beta = 0.036(0.027~0.045)] as well as decreased risk of incident dementia [increasing BMI by 1 is associated with HR of 0.981 (CI:0.969~0.992), N = 398782], but not changes in fluid intelligence or reaction time. Whole brain multiple regression analyses (volumetric analyses: N = 1253, other analyses: N = 1241) revealed positive associations between BMI and subsequent changes in regional gray matter volume (rGMV) in multiple areas, regional white matter volume changes in widespread white matter (WM) tracts, fractional anisotropy changes in several tracts, and intracellular volume fraction (ICVF) and orientation dispersion (OD) in widespread areas, and isotropic volume fraction (ISOVF) in a few areas, and negative associations between BMI and subsequent changes in rGMV in the bilateral medial temporal lobe areas, mean, axial and radial diffusivity, and ISOVF in widespread areas. These results are mostly consistent with the view that less BMI precedes greater neurocognitive aging or atrophy, with a few exceptions including OD findings and the rGMV finding of the medial temporal lobes as most of significant longitudinal associations of higher BMI were opposite to those seen in higher age and dementia. Future epidemiological studies should consider separating effects of higher BMI itself from potential confounders.

Epilepsy is a common chronic neurological disease that is characterized by spontaneous seizures. It is commonly comorbid with behavioral and mood disorders. No studies have yet examined the behavioral or structural brain changes associated with coriaria lactone (CL)-induced and pentylenetetrazol (PTZ)-induced kindlings. This study examined whether the increased seizure susceptibility induced by CL/PTZ is accompanied by behavioral impairments and aimed to identify associated structural brain changes. Kindling models were induced using CL and PTZ, with 10 rats in each group. After successful kindling, rats were subjected to brain structural imaging using T2-weighted imaging and underwent behavioral tests, namely, the open field test, water maze tasks, and contextual fear conditioning. Voxel-based morphometry was then used to identify possible brain structural changes associated with kindling and/or behaviors. Support-vector machine learning was also applied for the integrative analysis of behavioral changes and structural brain imaging. In the open field test, both the CL (P = 0.04) and PTZ groups (P = 0.002) spent more time in the central area than the control group. Only the PTZ group (50.29 ± 29.56 s) showed a freezing time that was significantly less than that of the control group (94.8 ± 41.04 s; P = 0.024, Tukey\'s HSD-corrected) in contextual fear conditioning, which is suggestive of impaired fear-associated learning ability. Furthermore, brain imaging analysis revealed that the gray matter volume (GMV) of the hippocampus changed in both the CL and PTZ groups when compared to control. The support-vector machine learning model indicated that the retrosplenial dysgranular and primary somatosensory cortices were associated with both of the mentioned kindling models. Furthermore, the support-vector regression model results indicated that kindling-associated GMV changes can be used to predict general exploratory activity in the open field test. In conclusion, this is the first study to report greater general exploratory activity in a CL-induced kindling model. Moreover, the general exploratory activity in the open field test can be predicted by the GMV of brain regions associated with kindling.

Intact Disc1-L100P mice carrying a point mutation DISC1Rgsc1390 in the second exon of the DISC1 gene (genetic model of schizophrenia) differ from the parental C57BL/6NCrl strain by higher content of CD3+ T cells and reduced number of CD19+B cells in the peripheral blood and spleen. Analysis of T cell subpopulations revealed an increase in the number of CD3+CD4+ T helpers in the blood of mutant mice and a decrease in the level of CD3+CD8+ suppressor/cytotoxic T cells and CD3+CD4+CD25+ T-regulatory cells. The distribution pattern of inflammatory (IL-1β, IL-2, IL-6, IL-17, IFNγ, and TNFα) and anti-inflammatory (IL-4, IL-10) cytokines specific for Disc1-L100P mice was revealed in the brain structures involved in the pathogenesis of schizophrenia. A possible implication of immune mechanisms in the development of schizophrenia-like endophenotype of Disc1-L100P mice is discussed.

The sex steroid hormones (SSHs) play several roles in regulation of various processes in the cardiovascular, immune, muscular and neural systems. SSHs affect prenatal and postnatal development of various brain structures, including regions associated with important physiological, behavioral, cognitive, and emotional functions. This action can be mediated by either intracellular or transmembrane receptors. While the classical mechanisms of SSHs action are relatively well examined, the physiological importance of non-classical mechanism of SSHs action through membrane-associated and transmembrane receptors in the brain remains unclear. The most recent summary describing the role of SSHs in different body systems is lacking. Therefore, the aim of this review is to discuss classical and non-classical signaling pathways of testosterone and estradiol action via their receptors at functional, cellular, tissue level and to describe the effects on various body systems and behavior. Particular emphasis will be on brain regions including the hippocampus, hypothalamus, frontal cortex and cerebellum.