Microglial Reaction in the Rat Cerebral Cortex Induced by Cortical Spreading Depression

The response of microglial cells to cortical spreading depression (CSD) was studied in rat brain by immunocytochemistry. CSD was elicited for one hour by the topical application of 4M potassium chloride solution and the microglial reaction examined immunocytochemically after 4, 16, 24 and 72 hours. CSD was sufficient to induce a microglial reaction throughout the cortex at 24 hours. Activated microglial cells furthermore showed a striking de-novo expression of major histocompatibility complex class II antigens. In contrast, no microglial reaction was observed in the cortex of sham-operated animals. This microglial reaction in response to CSD was not associated with histologically detectable neuronal damage. These results support the view that microglial cells are extremely sensitive to changes of the brain microenvironment. Their activation may be related to changes of ion homeostasis in the brain which are not sufficient to trigger neuronal injury.     

Alpha-thalassemia/mental retardation syndrome in a 45,X male

An unbalanced Y;autosome translocation leading to a male with a 45,X karyotype is rare with about 30 published cases. A male with a 45,X karyotype as a result of a unique, submicroscopic, unbalanced Y;16 translocation is presented with alpha-thalassemia/mental retardation syndrome.     

Effects of a feed additive blend on broilers challenged with heat stress

ABSTRACT

We evaluated a blend of medium-chain fatty acids (MCFA), organic acids, and a polyphenol antioxidant on gut integrity. Eighty Ross Broilers were exposed to 20–22°C (control – normothermic) or to 35–39.5°C (heat stress) for eight hours a day for a period of 1 or 5 days. Birds were fed a standard diet, or a diet supplemented with the test blend. Thereafter, birds were euthanized, and intestinal sections were excised for morphological, morphometric and gene expression analyses. Blood samples were collected for glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px) activity and trolox equivalent antioxidant capacity (TEAC) determination. Heart and liver tissues were used to quantify the expression of heat shock proteins 60 and 70 (HSP60 and HSP70, respectively) and inhibitor of kappa light chain gene enhancer in B cells alpha (IKBA). The jejunum was the most sensitive intestinal section, where heat stress modulated the expression of HSP70, of the inflammatory markers IKBA, interleukin 8 (IL-8), interferon gamma (IFNγ), and toll-like receptor 4 (TLR4). Moreover, expression of tight junctions (CLDN1, ZO1 and ZO2) and nutrient transporters (PEPT1 and EAAT3) was modulated especially in the jejunum. In conclusion, the feed additive blend protected intestines during heat stress from the decrease in villus height and crypt depth, and from the increase in villus width. Especially in the jejunum, heat stress played an important role by modulating oxidative stress and inflammation, impairing gut integrity and nutrient transport, and such deleterious effects were alleviated by the feed additive blend.

RESEARCH HIGHLIGHTS

• Jejunum is the most sensitive intestinal segment during heat stress.

• Heat stress affects the expression of tight junctions and nutrient transporters.

• Feed management helps to alleviate the disturbances caused by heat stress.

• A blend of MCFA, organic acids and a polyphenol protects broilers under heat stress.

     

Reproductive planning after genetic counselling: a perspective from the last decade

Studies from the last decade on factors influencing reproductive planning after genetic counselling were reviewed. Increased possibilities of DNA-analysis and prenatal diagnosis might have brought about a shift in the paramountcy of factors influencing reproductive planning after genetic counselling. In contrast to the literature in the seventies, the magnitude of the genetic risk was no longer found to be one of the decisive factors in postcounselling reproductive planning. Instead, the interpretation of the risk as high or low and the desire to have children appeared to be paramount. The impact of new developments in DNA-analysis in prenatal diagnosis and presymptomatic testing will be an important subject for future studies on factors influencing reproductive planning.     

Circulating leucocyte subpopulations in sedentary subjects following graded maximal exercise with hypoxia

Summary Ten healthy sedentary subjects [age, 27.5 (SD 3.5) years; height, 180 (SD 5) cm; mass, 69.3 (SD 6.3) kg] performed two periods of maximal incremental graded cycle ergometer exercise in a supine position. Randomly ordered and using an open spirometric system, one exercise was carried out during normoxia [maximal oxygen consumption ( O_2max)=38.6 (SD 3.5) ml·min^–1·kg^–1; maximal blood lactate concentration, 9.86 (SD 1.85) mmol·l^–1; test duration, 22.6 (SD 2.7) min], the other during hypoxia [ O_2max=33.2 (SD 3.2) ml·min^–1· kg^–1; maximal blood lactate concentration, 10.38 (SD 2.02) mmol·l^–1; test duration, 19.7 (SD 2.8) min]. At rest, immediately (0 p) and 60 min (60 p) after exercise, counts of leucocyte subpopulations (flow cytometry), cortisol and catecholamine concentrations were determined. At 0 p in contrast to normoxia, during hypoxia there was no significant increase of granulocytes. There were no significant differences between normoxia and hypoxia in the increases from rest to 0 p in counts of monocytes, total lymphocytes and lymphocyte subpopulations [clusters of differentiation (CD), CD3⁺, CD4⁺CD45RO^–, CD4⁺CD45RO⁺, CD8⁺CD45RO^–, CD8⁺CD45RO⁺, CD3⁺HLA-DR⁺, CD3^–CD16/CD56⁺, CD3⁺CD16/CD56⁺, CD 19⁺] as well as adrenaline, noradrenaline and cortisol concentrations. The counts of CD3 ^–CD16/CD56⁺-and CD8 ⁺CD45RO⁺-cells increased most. At 60 p, CD3^–CD16/CD56⁺ and CD3⁺CD16/CD56⁺-cell counts were below pre-exercise levels and under hypoxia slightly but significantly lower than under normoxia. We concluded that the exercise-induced mobilization and redistribution of most leucocyte and lymphocyte subpopulations were unimpaired under acute hypoxia at sea level. Reduced increases of granulocyte counts during the study and reduced cell numbers of natural killer cells and cytotoxic, not major histocompatibility complex-restricted T-cells, only indicated marginal effects on the immune system.     

Source Localization of P300 from Oddball, Single Stimulus, and Omitted-Stimulus Paradigms

Three different auditory stimulus paradigms were used to elicit P300 potentials. Normal subjects were tested on the classical rare target stimulus, single-stimulus and omitted-stimulus conditions. Noninvasive identification of the cerebral sources of the event-related potentials (ERPs) was performed using spatio-temporal multiple dipole modeling (BESA software) with individually sized spherical head models. The grand average data of each condition was first independently modeled and these models were used as starting values for modeling each individual subject's data. Models for the rare-stimulus condition and single-stimulus condition both consisted of 6 dipoles. Models for the omitted-stimulus condition consisted of 2 dipoles. The dipole locations of the final individual 6-dipole models for the rare and single-stimulus conditions did not differ significantly from each other or from one previous result obtained from a another group of subjects (Tarkka et al. 1995). Super-imposition of the dipole coordinates on the sterotaxic brain atlas suggests that bilateral deep medial temporal lobe structures are the major contributors to rare and single-stimulus P300s. Because both the wave form morphology and the source model of the P300 elicited by single stimulus were close to those of the rare-stimulus P300 it may be that the underlying neural mechanisms eliciting these P300 potentials are essentially the same.     

Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade.     

Chromosomal radiosensitivity of breast cancer with a CHEK2 mutation

Recently, multiple studies have shown that a sequence variant in CHEK2 (CHEK2 1100delC) plays a role in the susceptibility to breast cancer. This mutation should confer about a twofold increased breast cancer risk in women and a 10-fold increased risk in men. Because the CHEK2 gene plays a critical role in DNA damage repair and the CHEK2 1100delC variant confers susceptibility to breast cancer, we investigated if patients carrying the CHEK2 1100delC mutation are characterized by an enhanced chromosomal radiosensitivity. To this end, familial breast cancer patients, sporadic breast cancer patients, and healthy women, considered in our previously studied to determine their chromosomal radiosensitivity with the G2 and G0-MN assay, were all tested in present study for the presence of the CHEK2 1100delC variant. The 1100delC variant was detected in none of the 100 healthy individuals, in 1 of 100 (1%) unselected breast cancer patients and in 3 of 78 (3.8%) breast cancer patients with a family history of breast cancer. The breast cancer patients with the CHEK2 1100delC genotype had a mean radiation-induced yield of chromatid breaks that was not significantly different from that of the healthy control group. Although the mean yield of micronuclei (MN) was significantly higher compared to the healthy control group, this higher mean MN yield was due to a single patient who had a very high number of MN compared to the parallel control. Our data suggest that breast cancer patients with a CHEK2 1100delC mutation are in general not characterized by a distinct enhanced chromosomal radiosensitivity. These conclusions are, however, very preliminary, because of the small numbers of CHEK2 1100delC breast cancer patients studied.     

Encoding of visceral noxious stimuli in the discharge patterns of visceral afferent fibres from the colon

Afferent fibres, in the inferior splanchnic nerves and lumbar white rami, which supply the colon and its mesentery in the cat, were investigated for their responses to distension and contraction of the colon and to local pressure applied to colon and its mesentery. 1) 63% (177 out of 287) of the axons had resting activity (median 0.3 imp/s). These axons were either unmyelinated (conduction velocity below 2 m/s) or thin myelinated (conduction velocity below 18 m/s). Most axons without resting activity (N=95 out of 106 axons) conducted at less than 1.4 m/s, and most were probably sympathetic efferents. 2) 76 out of 80 afferent units with resting activity (95%) and 8 out of 27 units without (30%) were excited by distension of the colon. The thresholds were largely at intraluminal pressures of around 25 mm Hg or higher. 3) Most afferent units (87%) responded with an increased steady state discharge throughout the distension with or without initial dynamic response. The rest of the afferent units responded only with a transient discharged to distension. 4) Most afferent units reacted in a graded manner to variable intraluminal pressures. 5) In only 43% of the distension-sensitive afferent units could mechanoreceptive sites be located on the wall of the colon or in the mesentery. The majority of the afferent units had one mechanoreceptive site only, some had two. 6) Afferent units reacting to colon distension were also excited by contraction of the colon. 7) The excitability spectrum of visceral afferent fibres in the inferior splanchnic nerves, which are activated by colon distension, suggests that these units are involved in visceral nociception from the colon.