Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum.
ABSTRACT: Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA) mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons. The corpus callosum (CC) is the largest white matter tract in mammals, and more than 99% of the cell somata correspond to glial cells in rodents. Whether glial cell density is altered in anorexia is unknown. Thus, the aim of this study was to estimate glial cell density in the three main regions of the CC (genu, body, and splenium) in a murine model of DIA. The astrocyte density was significantly reduced (~34%) for the DIA group in the body of the CC, whereas in the genu and the splenium no significant changes were observed. DIA and forced food restriction (FFR) also reduced the ratio of astrocytes to glial cells by 57.5% and 22%, respectively, in the body of CC. Thus, we conclude that DIA reduces astrocyte density only in the body of the rat CC.
Project description:<b>Objective: </b>To investigate the quantitative diffusion properties of the corpus callosum (CC) in a large group of patients with periventricular nodular heterotopia (PNH) related epilepsy and to further investigate the effect of <i>Filamin A</i> (<i>FLNA</i>) mutation on these properties.<br><br><b>Methods: </b>Patients with PNH (n = 34), subdivided into <i>FLNA</i>-mutated (n = 11) and <i>FLNA</i>-nonmutated patients (n = 23) and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion imaging scan (64 direction). Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the three major subdivisions of the CC (genu, body and splenium). Correlations between DTI metric changes and clinical parameters were also evaluated. Furthermore, the effect of <i>FLNA</i> mutation on structural integrity of the corpus callosum was examined.<br><br><b>Results: </b>Patients with PNH and epilepsy had significant reductions in FA for the genu and splenium of the CC, accompanied by increases in MD for the splenium, as compared to healthy controls. There were no correlations between clinical parameters of epilepsy and MD. The FA value in the splenium negatively correlated with epilepsy duration. Interestingly, <i>FLNA</i>-mutated patients showed significantly decreased FA for all three major subdivisions of the CC, and increased MD for the genu and splenium, as compared to HCs and <i>FLNA</i>-nonmutated patients.<br><br><b>Conclusions: </b>These findings support the conclusion that patients with epilepsy secondary to PNH present widespread microstructural changes found in the corpus callosum that extend beyond the macroscopic MRI-visible lesions. This study also indicates that <i>FLNA</i> may affect white matter integrity in this disorder.
Project description:Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (-23%) and dentate gyrus (-48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.
Project description:PURPOSE:Frequency difference mapping (FDM) is a phase processing technique which characterizes the nonlinear temporal evolution of the phase of gradient echo (GE) signals. Here, a novel FDM-processing algorithm is introduced, which is shown to reveal information about white matter microstructure. Unlike some other phase-processing techniques, the FDM algorithm presented here does not require the use of phase unwrapping or sophisticated image processing. It uses a series of scaled complex divisions to unwrap phase and remove background fields. METHODS:Ten healthy subjects underwent a series of single-slice, sagittal multi-echo GE scans at 7T with the slice positioned at the midline. Phase data were processed with the novel FDM algorithm, and the temporal evolution of the magnitude signal and frequency difference was examined in 5 regions of the corpus callosum (CC; genu, anterior body, middle body, posterior body, and splenium). RESULTS:Consistent frequency difference contrast relative to surrounding tissue was observed in all subjects in the CC and in other white matter regions where the nerve fibers run perpendicular to B0 , such as the superior cerebellar peduncle. Examination of the frequency difference curves shows distinct variations over the CC, with the genu and splenium displaying larger frequency differences than the other regions (in addition to a faster decay of signal magnitude). CONCLUSION:The novel FDM algorithm presented here yields images sensitive to tissue microstructure and microstructural differences over the CC in a simple manner, without the requirement for phase unwrapping or sophisticated image processing.
Project description:Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with neurocognitive impairments. The neural substrates of cognitive impairments in 22q11DS remain poorly understood. Because the corpus callosum (CC) is found to be abnormal in a variety of neurodevelopmental disorders, we obtained volumetric measurements of the CC and its subregions, examined the relationship between these regions and neurocognition and selected genotypes within candidate genes in the 22q11.2 interval in 59 children with 22q11DS and 53 control subjects. The total CC, splenium and genu were significantly larger in children with 22q11DS and the enlargement was associated with better neurocognitive functioning in the 22q11DS group, suggestive of a compensatory increase in the CC volumes. The expected age-related increase in the volume of the CC was not seen in children with 22q11DS, indicative of dysmaturation of the CC in these children. The increased volumes in the genu, splenium and total CC in the 22q11DS group were associated with polymorphisms within the candidate genes: COMT (rs4680), ZDHHC8 (rs175174) and UFD1L (rs5992403). These findings indicate that alterations in the CC volume in children with 22q11DS are associated with cognition and specific genotypes in the 22q11.2 interval.
Project description:Objective:Although many studies have shown that the corpus callosum (CC) may play an important role in bipolar disorder (BD) and suicide, the pathophysiological mechanism of BD underlying suicidal behavior is still unclear. This study aimed to explore the relationship between the CC, and BD and suicidal ideation using diffusion tensor imaging (DTI). Method:A total of 203 participants (47 BD patients with suicidal ideation, 59 with BD without suicidal ideation, and 97 healthy controls [HC]) underwent DTI scanning at a single site. We examined the white matter integrity of the CC in the three groups. Results:A comparison among groups showed that BD patients with suicidal ideation had significant lower fractional anisotropy (FA) values than those of BD without suicidal ideation and HCs in the body and genu of the CC, and FA values of BD without suicidal ideation were significantly lower than those of HCs. However, in the splenium of corpus callosum, no difference was found between BD without suicidal ideation and HCs. Conclusions:Our findings add to the evidence suggesting that the CC plays a key role in BD with suicidal ideation, especially with respect to the role of the genu and body of the CC subserving emotion regulation.
Project description:Traumatic brain injury (TBI) often leads to impaired consciousness. Recent diffusion tensor imaging studies associated consciousness with imaging metrics including fractional anisotropy (FA) and apparent diffusion coefficient (ADC). We evaluated their correlations and determined the best index in candidate regions. Six databases were searched, including PubMed and Embase, and 16 studies with 701 participants were included. Data from region-of-interest and whole-brain analysis methods were meta-analysed separately. The FA-consciousness correlation was marginal in the whole-brain white matter (r?=?0.63, 95% CI [0.47, 0.79], p?=?0.000) and the corpus callosum (CC) (r?=?0.60, 95% CI [0.48, 0.71], p?=?0.000), and moderate in the internal capsule (r?=?0.48, 95% CI [0.24, 0.72], p?=?0.000). Correlations with ADC trended negative and lacked significance. Further subgroup analysis revealed that consciousness levels correlated strongly with FA in the CC body (r?=?0.66, 95% CI [0.43, 0.89]), moderately in the splenium (r?=?0.58, 95% CI [0.38, 0.78]), but insignificantly in the genu. In conclusion, FA correlates better with consciousness levels than ADC in TBI. The degree of correlation varies among brain regions. The CC (especially its splenium and body) is a reliable candidate region to quantitatively reflect consciousness levels.
Project description:Children with unilateral spastic cerebral palsy (USCP) have shown impaired bimanual coordination. The corpus callosum (CC) connects the two hemispheres and is critical for tasks that require inter-hemisphere communication. The relationship between the functional bimanual coordination impairments and structural integrity of the CC is unclear. We hypothesized that better integrity of the CC would relate to better bimanual coordination performance during a kinematic bimanual drawer-opening task. Thirty-nine children with USCP (Age: 6-17 years old; MACS levels: I-III) participated in the study. Measurement of the CC integrity was performed using diffusion tensor imaging. The CC was measured as a whole and was also divided into three regions: genu, midbody, and splenium. Fractional anisotropy, axial diffusivity (AD), radial diffusivity, mean diffusivity, number of voxels, and number of streamlines were evaluated in whole and within each region of the CC. 3-D kinematic analyses of bimanual coordination were also assessed while children performed the bimanual task. There were negative correlations between bimanual coordination measures of total movement time and AD of whole CC (p = 0.037), number of streamlines and voxels of splenium (p = 0.038, 0.032, respectively); goal synchronization and AD of whole CC (p = 0.04), and number of streamlines and voxels of splenium (p = 0.001, 0.01, respectively). The current results highlight the possible connection between the integrity of the CC, especially between the splenium region and temporal bimanual coordination performance for children with USCP.
Project description:The corpus callosum (CC) provides the main route of communication between the 2 hemispheres of the brain. In monkeys, chimpanzees, and humans, callosal axons of distinct size interconnect functionally different cortical areas. Thinner axons in the genu and in the posterior body of the CC interconnect the prefrontal and parietal areas, respectively, and thicker axons in the midbody and in the splenium interconnect primary motor, somatosensory, and visual areas. At all locations, axon diameter, and hence its conduction velocity, increases slightly in the chimpanzee compared with the macaque because of an increased number of large axons but not between the chimpanzee and man. This, together with the longer connections in larger brains, doubles the expected conduction delays between the hemispheres, from macaque to man, and amplifies their range about 3-fold. These changes can have several consequences for cortical dynamics, particularly on the cycle of interhemispheric oscillators.
Project description:Alzheimer's Disease (AD) is a neurodegenerative disorder that mainly affects grey matter (GM). Nevertheless, a number of investigations have documented white matter (WM) pathology associated with AD. The corpus callosum (CC) is the largest WM fiber bundle in the human brain. It has been shown to be susceptible to atrophy in AD mainly as a correlate of Wallerian degeneration of commissural nerve fibers of the neocortex. The aim of this study was to investigate which callosal regions are affected and whether callosal degeneration is associated with the stage of the disease. For this purpose, we analyzed high-resolution MRI data of patients with amnesic mild cognitive impairment (MCI) (n=20), mild AD (n=20), severe AD (n=10), and of healthy controls (n=20). Callosal morphology was investigated applying two different structural techniques: mesh-based geometrical modeling methods and whole-brain voxel-based analyses. Our findings indicate significant reductions in severe AD patients compared to healthy controls in anterior (genu and anterior body) and posterior (splenium) sections. In contrast, differences between healthy controls and mild AD patients or amnesic MCI patients were less pronounced and did not survive corrections for multiple comparisons. When correlating anterior and posterior WM density of the CC with GM density of the cortex in the severe AD group, we detected significant positive relationships between posterior sections of the CC and the cortex. We conclude that callosal atrophy is present predominantly in the latest stage of AD, where two mechanisms might contribute to WM alterations in severe AD: the Wallerian degeneration in posterior subregions and the myelin breakdown process in anterior subregions.
Project description:BACKGROUND AND PURPOSE:Mild traumatic brain injury is a leading cause of death and disability worldwide with 42 million cases reported annually, increasing the need to understand the underlying pathophysiology because this could help guide the development of targeted therapy. White matter, particularly the corpus callosum, is susceptible to injury. Animal models suggest stretch-induced mechanoporation of the axonal membrane resulting in ionic shifts and altered sodium ion distribution. The purpose of this study was to compare the distribution of total sodium concentration in the corpus callosum between patients with mild traumatic brain injury and controls using sodium (23Na) MR imaging. MATERIALS AND METHODS:Eleven patients with a history of mild traumatic brain injury and 10 age- and sex-matched controls underwent sodium (23Na) MR imaging using a 3T scanner. Total sodium concentration was measured in the genu, body, and splenium of the corpus callosum with 5-mm ROIs; total sodium concentration of the genu-to-splenium ratio was calculated and compared between patients and controls. RESULTS:Higher total sodium concentration in the genu (49.28 versus 43.29 mmol/L, P = .01) and lower total sodium concentration in the splenium (which was not statistically significant; 38.35 versus 44.06 mmol/L, P = .08) was seen in patients with mild traumatic brain injury compared with controls. The ratio of genu total sodium concentration to splenium total sodium concentration was also higher in patients with mild traumatic brain injury (1.3 versus 1.01, P = .001). CONCLUSIONS:Complex differences are seen in callosal total sodium concentration in symptomatic patients with mild traumatic brain injury, supporting the notion of ionic dysfunction in the pathogenesis of mild traumatic brain injury. The total sodium concentration appears to be altered beyond the immediate postinjury phase, and further work is needed to understand the relationship to persistent symptoms and outcome.