Synaptic changes in cortical and subcortical brain formations in old rats

Electron microscopy was used to study structural changes of synapses in sensorimotor, parietal, limbic cortical areas, hippocamp, blue spot and hypothalamus of old Wistar rats, aged 28-30 months. Polymorphism of ultrastructural changes in neuronal and synapse processes and individual variability of these shifts in the brain of old rats have been revealed. The predominant damage of post-synaptic synapse components with ageing is demonstrated. Along with dystrophic and destructive changes in pre- and post-synaptic parts of the contact, signs of compensatory adaptive resettings in inter-neuronal links have been detected.     

Genetic associations with brain cortical thickness in multiple sclerosis

Multiple sclerosis (MS) is characterized by temporal and spatial dissemination of demyelinating lesions in the central nervous system. Associated neurodegenerative changes contributing to disability have been recognized even at early disease stages. Recent studies show the importance of gray matter damage for the accrual of clinical disability rather than white matter where demyelination is easily visualized by magnetic resonance imaging (MRI). The susceptibility to MS is influenced by genetic risk, but genetic factors associated with the disability are not known. We used MRI data to determine cortical thickness in 557 MS cases and 75 controls and in another cohort of 219 cases. We identified nine areas showing different thickness between cases and controls (regions of interest, ROI) (eight of them were negatively correlated with Kurtzke's expanded disability status scale, EDSS) and conducted genome‐wide association studies (GWAS) in 464 and 211 cases available from the two data sets. No marker exceeded genome‐wide significance in the discovery cohort. We next combined nominal statistical evidence of association with physical evidence of interaction from a curated human protein interaction network, and searched for subnetworks enriched with nominally associated genes and for commonalities between the two data sets. This network‐based pathway analysis of GWAS detected gene sets involved in glutamate signaling, neural development and an adjustment of intracellular calcium concentration. We report here for the first time gene sets associated with cortical thinning of MS. These genes are potentially correlated with disability of MS.     

Relations among alveolar surface tension, surface area, volume, and recoil pressure

For pulmonary structure-function analysis excised rabbit lungs were fixed by vascular perfusion at six points on the pressure-volume (P-V) curve, i.e. at 40, 80, and 100% of total lung capacity (TLC) on inflation, at 80 and 40% TLC on deflation, and at 80% TLC on reinflation. Before fixation alveolar surface tensions (gamma) were measured in individual alveoli over the entire P-V loop, using an improved microdroplet method. A maximal gamma of approximately 30 mN/m was measured at TLC, which decreased during lung deflation to about 1 mN/m at 40% TLC. Surface tensions were considerably higher on the inflation limb starting from zero pressure than on the deflation limb (gamma-V hysteresis). In contrast, the corresponding alveolar surface area-volume (SA-V) relationship did not form a complete hysteresis over the entire volume range. There was a considerable difference in SA between lungs inflated to 40% TLC (1.49 +/- 0.11 m2) and lungs deflated to 40% TLC (2.19 +/- 0.21 m2), but at 80% TLC the values of SA were essentially the same regardless of the volume history. The data indicate that the gamma-SA hysteresis is only in part accountable for the P-V hysteresis and that the determinative factors of alveolar geometry change with lung volume. At low lung volumes airspace dimensions appear to be governed by an interplay between surface and tissue forces. At higher lung volumes the tissue forces become predominant.     

Classification of first-episode schizophrenia patients and healthy subjects by automated MRI measures of regional brain volume and cortical thickness

Background

Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls.

Method

Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis.

Results

Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%.

Conclusion

Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia.     

Correction of changes induced by toluene in the cortical and subcortical structures of albino rat brain

The number and weight of cells in the cortical and subcortical structures of the cerebral and cerebellar motor system in albino rats after a long-term exposure to toluene were determined. Toluene intoxication proved to kill projection neurons and interneurons in the sensorimotor cortex, ventrolateral thalamic nucleus, caudate nucleus, pallidum, red nucleus, and inferior olivary complex. The decreased number of cerebellar cells was mediated by atrophic changes as indicated by the decrease in the area and dry weight of Purkinje cells. The addition of plaferon LB to the diet attenuated the cytotoxic effect of toluene.     

A genome‐wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus

Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is highly variable across individuals. This variability has been linked to sound perception ability in both speech and music domains. Previous studies show that variations in morphological features of HG, such as cortical surface area and thickness, are heritable. To identify genetic variants that affect HG morphology, we conducted a genome‐wide association scan (GWAS) meta‐analysis in 3054 healthy individuals using HG surface area and thickness as quantitative traits. None of the single nucleotide polymorphisms (SNPs) showed association P values that would survive correction for multiple testing over the genome. The most significant association was found between right HG area and SNP rs72932726 close to gene DCBLD2 (3q12.1; P = 2.77 × 10^?7). This SNP was also associated with other regions involved in speech processing. The SNP rs333332 within gene KALRN (3q21.2; P = 2.27 × 10^?6) and rs143000161 near gene COBLL1 (2q24.3; P = 2.40 × 10^?6) were associated with the area and thickness of left HG, respectively. Both genes are involved in the development of the nervous system. The SNP rs7062395 close to the X‐linked deafness gene POU3F4 was associated with right HG thickness (Xq21.1; P = 2.38 × 10^?6). This is the first molecular genetic analysis of variability in HG morphology.     

Regional variations in cortical modeling in the femoral mid-shaft: sex and age differences

Modern lifestyle changes may result in site-specific alterations in the skeleton. Our aim was to determine sex and age differences in regional geometry at the mid-femur. Complete cross sections from 113 individuals aged 20-97 years from a modern Australian population were obtained. A further subsample of 24, in whom the precise orientation of specimens was known, was subsequently collected. Microradiographs were made of 100-microm sections and the bone was analyzed using image processing software (Optimas, Media Cybernetics). The periosteal boundary was extracted automatically and the centroid of the periosteal outline was calculated. Fourier shape analysis was used to delineate the endocortical surface. Radial and cortical widths in each quadrant were determined. The posterior was identified by the linea aspera, and the medial and lateral were indistinguishable and therefore grouped together. For analysis, the entire sample was divided into three groups: young (20-40 years), middle (41-60 years), and old (61+ years). Raw and height-normalized values were analyzed with SPSS using t-tests, analysis of variance, and Tukey's honestly significant difference (HSD) tests. The results show that with age the femoral mid-shaft in both sexes becomes larger and more circular, with a slight shift towards the anterior. Apposition is least on the posterior and resorption greatest on the anterior, the latter being particularly evident in postmenopausal females. The greatest sex differences are seen in the middle years, lessening again in the old. We conclude that differential circumferential modeling in response to functional and postural changes occurs in both sexes with age.     

Regional and species differences in endogenous prostaglandin biosynthesis by brain homogenates

Endogenously formed prostaglandins (PGs) D₂, E₂ and F_2α were determined in homogenates of brain regions from rat, guinea-pig, rabbit and cat, using gas-chromatography-mass spectrometry. The main PGs formed in the brain regions of the rat were PGD₂, in the guinea-pig PGD₂ and PGF_2α, in the rabbit PGF_2α and in the cat PGE₂. Brain regions from the same animal species showed the same pattern of PG formation. They varied, however, in the amount of total PGs formed, the limbic system and the cerebral cortex being highest and cerebellum lowest.     

Regional blood volume and peripheral blood flow in postural tachycardia syndrome

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.