Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion increases the risk of neuropsychiatric disorders like autism and schizophrenia. Disruption of large-scale functional connectivity in 22q11 deletion syndrome (22q11DS) has been widely reported, but the biological factors driving these changes remain unclear.

Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation.

The course of normal development and response to pathology are strongly influenced by biological sex. For instance, female childhood cancer survivors who have undergone cranial radiation therapy (CRT) tend to display more pronounced cognitive deficits than their male counterparts. Sex effects can be the result of sex chromosome complement (XX vs.

Sex-biasing influence of autism-associated gene overdosage at connectomic, behavioral, and transcriptomic levels.

Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene () affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases.

Mapping and comparing fMRI connectivity networks across species.

Technical advances in neuroimaging, notably in fMRI, have allowed distributed patterns of functional connectivity to be mapped in the human brain with increasing spatiotemporal resolution. Recent years have seen a growing interest in extending this approach to rodents and non-human primates to understand the mechanism of fMRI connectivity and complement human investigations of the functional connectome. Here, we discuss current challenges and opportunities of fMRI connectivity mapping across species.

Exercise promotes growth and rescues volume deficits in the hippocampus after cranial radiation in young mice.

Human and animal studies suggest that exercise promotes healthy brain development and function, including promoting hippocampal growth. Childhood cancer survivors that have received cranial radiotherapy exhibit hippocampal volume deficits and are at risk of impaired cognitive function, thus they may benefit from regular exercise. While morphological changes induced by exercise have been characterized using magnetic resonance imaging (MRI) in humans and animal models, evaluation of changes across the brain through development and following cranial radiation is lacking.

Protection From Radiation-Induced Neuroanatomic Deficits by CCL2 Deficiency Is Dependent on Sex.

Purpose: Cranial radiation therapy for the treatment of pediatric brain tumors results in changes to brain development that are detectable with magnetic resonance imaging. We have previously demonstrated similar structural changes in both humans and mice. The goal of the current study was to examine the role of inflammation in this response.

Unique spatiotemporal fMRI dynamics in the awake mouse brain.

Human imaging studies have shown that spontaneous brain activity exhibits stereotypic spatiotemporal reorganization in awake, conscious conditions with respect to minimally conscious states. However, whether and how this phenomenon can be generalized to lower mammalian species remains unclear. Leveraging a robust protocol for resting-state fMRI (rsfMRI) mapping in non-anesthetized, head-fixed mice, we investigated functional network topography and dynamic structure of spontaneous brain activity in wakeful animals.

Arginase-1 deficiency in neural cells does not contribute to neurodevelopment or functional outcomes after sciatic nerve injury.

Arginase-1 (Arg1) is an enzyme controlling the final step of the urea cycle, with highest expression in the liver and lower expression in the lungs, pancreas, kidney, and some blood cells. Arg1 deficiency is an inherited urea cycle disorder presenting with neurological dysfunction including spastic diplegia, intellectual and growth retardation, and encephalopathy. The contribution of Arg1 expression in the central and peripheral nervous system to the development of neurological phenotypes remains largely unknown.

p53 Loss Mitigates Early Volume Deficits in the Brains of Irradiated Young Mice.

Purpose: Pediatric cranial radiation therapy results in lasting changes in brain structure. Though different facets of radiation response have been characterized, the relative contributions of each to altered development is unclear. We sought to determine the role of radiation-induced programmed cell death, as mediated by the Trp53 (p53) gene, on neuroanatomic development.

Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry.

Ex vivo magnetic resonance imaging (MRI) requires chemical fixation to preserve tissue during storage or extended imaging sessions. Although it is commonly understood that fixation may alter tissue volume and shape, the potential confounding effects of fixation and storage on morphometric analyses have not been well characterized. With increasing use of ex vivo MRI for mouse brain phenotying and opportunities for inter-study comparisons, we sought to characterize how changes in fixation and/or storage times affected tissue volume, and how this might impact phenotyping results.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice.

Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species.

Treatment age, dose and sex determine neuroanatomical outcome in irradiated juvenile mice.

Pediatric cranial radiation therapy can induce long-term neurocognitive deficits, the risk and severity of these deficits are amplified in females and in those individuals exposed at a younger age and/or those irradiated at higher doses. To investigate the developmental consequences of these factors in greater detail, male and female C57Bl/6J mice between infancy and late childhood (16 and 36 days) were irradiated at a single time point with a whole-brain dose of 0, 3, 5 or 7 Gy. In vivo and ex vivo magnetic resonance imaging (MRI) and deformation-based morphometry was used to identify radiation-induced volume differences.