Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

NEW FINDINGS: What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the hypothalamus of 3-month-old ISIAH rats, an increase in energetic activity and prevalence of excitatory over inhibitory neurotransmitters was noticed. The blood flow through the main arteries showed a positive correlation with glutamate and glutamine levels in the hypothalamus and a negative correlation with the hypothalamic GABA level. The blood pressure values were positively correlated with hypothalamic choline levels. Thus, the early development of stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries.

Alteration of the brain morphology and the response to the acute stress in the recombinant mouse lines with different predisposition to catalepsy.

Catalepsy is an inability to correct an externally imposed awkward posture; it is associated with schizophrenia and depression in human. We created new recombinant B6.CBA-D13Mit76C and B6.CBA-D13Mit76B mouse lines on the C57Bl/6 genome, carrying the 102.73-110.56Mbp fragment of chromosome 13 derived from the catalepsy-prone CBA strain and catalepsy-resistant C57BL/6 strain, respectively. We compared the behavior and brain morphology (11.7T BioSpec 117/16 USR tomograph, Germany) in these lines. The effects of acute emotional stress on corticosterone's level in the blood and mRNA expression of Bdnf and Arc genes in the brain were investigated. The B6.CBA-D13Mit76B mice were non-cataleptic, while about 17% of B6.CBA-D13Mit76C mice demonstrated catalepsy-like immobility. No difference between these lines was revealed in the open field and social interaction tests. In the Morris water maze test, both lines effectively found the platform on the fourth day; however B6.CBA-D13Mit76B mice achieved significantly better results than cataleptic-prone animals. B6.CBA-D13Mit76C mice were characterized by decreased volume of the total brain and reduced sizes of striatum, cerebellum and pituitary gland. The both lines showed the similar basal and stress-induced levels of corticosterone, while the brain expression of Bdnf and Arc genes was more vulnerable to stress in the catalepsy-prone B6.CBA-D13Mit76C line.

Alterations in pharmacological and behavioural responses in recombinant mouse line with an increased predisposition to catalepsy: role of the 5-HT1A receptor.

BACKGROUND AND PURPOSE: One important syndrome of psychiatric disorders in humans is catalepsy. Here, we created mice with different predispositions to catalepsy and analysed their pharmacological and behavioural properties. EXPERIMENTAL APPROACH: Two mouse lines, B6-M76C and B6-M76B, were created by transfer of the main locus of catalepsy containing the 5-HT1A receptor gene to the C57BL/6 genetic background. Behaviour, brain morphology, expression of key components of the serotoninergic system, and pharmacological responses to acute and chronic stimulation of the 5-HT1A receptor were compared. KEY RESULTS: B6-M76B mice were not cataleptic, whereas 14% of B6-M76C mice demonstrated catalepsy and decreased depressive-like behaviour. Acute administration of the 5-HT1A receptor agonist 8-OH-DPAT resulted in dose-dependent hypothermia and in decreased locomotion in both lines. Chronic 8-OH-DPAT administration abolished the 5-HT1A receptor-mediated hypothermic response in B6-M76C mice and increased locomotor activity in B6-M76B mice. In addition, 5-HT metabolism was significantly reduced in the hippocampus of B6-M76C mice, and this effect was accompanied by an increased expression of the 5-HT1A receptor. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that transfer of the main locus of hereditary catalepsy containing the 5-HT1A receptor from CBA mice to the C57BL/6 genetic background led to increased postsynaptic and decreased presynaptic functional responses of the 5-HT1A receptor. This characteristic establishes the B6-M76C line as an attractive model for the pharmacological screening of 5-HT1A receptor-related drugs specifically acting on either pre- or postsynaptic receptors. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.

[Study of patency of vascular grafts manufactured by means of electrospinning].

UNLABELLED: In vivo experiments were carried out to study functioning of vascular grafts manufactured by means of electrospinning from solutions of polycaprolactone (PCL) and hexafluoroisopropanol (HFIP), PCL with 10% gelatine and a low-permeability inner layer (LPIL) 10 µm thick and PCL with 10% gelatine and LPIL (10 µm) wherein as polymeric base instead of PCL copolymer of lactic and hydroxyacetic acids (polylactide-co-glycolide, PLGA) was used. The grafts were implanted into the infrarenal portion of the aorta to 45 rats, 15 rats for each type of the graft. Patency of artificial vessels was assessed by means of magnetic resonance tomography and diagnostic ultrasound Dopplerography at 2, 4 and 20 weeks (5 animals for each time point). The state of the graft and surrounding tissues was analysed by means of intraoperative assessment, survey microscopy and survey fluorescent microscopy. CONCLUSION: The obtained findings demonstrated that vascular grafts made by electrospinning technique with a low-permeability inner layer are less prone to formation of the neointima and stenosing as compared with grafts having no such layer.

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles.

[Aerosol deposition in nasal passages of burrowing and ground rodents when breathing dust-laden air].

In subterranean rodents, which dig down the passages with frontal teeth, adaptation to the underground mode of life presumes forming of mechanisms that provide protection against inhaling dust particles of different size when digging. One of such mechanisms can be specific pattern of air flow organization in the nasal cavity. To test this assumption, comparative study of geometry and aerodynamics of nasal passages has been conducted with regard to typical representative of subterranean rodents, the mole vole, and a representative of ground rodents, the house mouse. Numerical modeling of air flows and deposition of micro- and nanoparticle aerosols indicates that sedimentation of model particles over the whole surface of nasal cavity is higher in mole vole than in house mouse. On the contrary, particles deposition on the surface of olfactory epithelium turns out to be substantially less in the burrowing rodent as compared to the ground one. Adaptive significance of the latter observation has been substantiated by experimental study on the uptake ofnanoparticles of hydrated manganese oxide MnO x (H2O)x and Mn ions from nasal cavity into brain. It has been shown with use of magnetic resonance tomography method that there is no difference between studied species with respect to intake of particles or ions by olfactory bulb when they are introduced intranasally. Meanwhile, when inhaling nanoparticle aerosol of MnCl2, deposition of Mn in mouse's olfactory bulbs surpasses markedly that in vole's bulbs. Thereby, the morphology of nasal passages as a factor determining the aerodynamics of upper respiratory tract ensures for burrowing rodents more efficient protection of both lungs and brain against inhaled aerosols than for ground ones.

[Selection for catatonic reaction in rats: a study of interstrain differences by magnetic resonance imaging].

Brain studies by magnetic resonance imaging, angiography, and spectroscopy have been performed with rat strains Wistar, GC (genetic and catatonia), and PM+ (pendulum movements). Both GC and PM+ rats show similar deviations from the ancestral Wistar population in having smaller areas of the right striatum (coronal slice). The anterior horns of lateral ventricles in GC rats are smaller than in the control strain. The maximum blood flow velocity in the common carotid arteries of PM+ rats is greater. The GC and PM+ strains differ in myo-inositol level in the hippocampus. The PM+ strain is characterized by a lower taurine level in the hippocampus, which may be one of the participants regulated the predisposition to audiogenic seizures.

[Magnetic resonance spectroscopy of metabolic changes in mice brain after 2-deoxy-D-glucose injection].

In vivo proton magnetic resonance spectroscopy (1H MRS) of ICR male mice was used to study the brain (hippocampus) metabolic response to the acute deficiency of the available energy or to the pro-inflammatory stimulus. Inhibition of glycolysis by means of an intraperitoneal injection with 2-deoxy-D-glucose (2DG) reduced the levels of gamma-aminobutiric acid (GABA), N-acetylaspartate (NAA) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS)--a very common pro-inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred three hours after the injection of LPS. Different metabolic responses to the energy deficiency and the pro-inflammatory stimuli can explain the contradictory results of the brain MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. Prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, shifts brain metabolic pattern to prevalence of the inhibitory neurotransmitter GABA.

[The energetic cost of social behavior in mice under activation of the nonspecific immunity].

Using originally designed low inertial open circuit respirometer, we studied influence of the bacterial endotoxin on the bioenergetic gain of male mice, which they showed after 15 min pair-wise test. Injection of lipopolysaccharide (LPS) provided increase of the post pair-wise test energy metabolism and increase of the relative energy cost of each agonistic act in dominant males. Significant correlation between energy response and number of agonistic acts in the pair-wise test was found only for LPS treated males. Spontaneous activity measured before social conflict and non-agonistic behavior during pair-wise test did not correlate with energy metabolism. Since all behavioral acts need energy and since the significant correlation between energy response and behavioral activity was found only for the agonistic behavior we assume these relationships being a result of synergetic influence on the energy metabolism of both the nonspecific immune response on LPS and neuroendocrine accompaniment of the intermale aggression.

[Antigen stimulation modifies social behavior and chemosignals in male laboratory mice].

The injection of outbred ICR strain male mice with SRBC affected their dominance ability in pair-wise test. In pair-wise tests done without previous presentation of the smell of a contestant, the SRBC-treated males submitted to control males. This effect occurred within 3 days after the injection. However, on the third day after treatment, under conditions of getting pre-test olfactory information about a contestant, the dominance of SRBC treated-males over the control animals was observed. Perception of the contestant smell is known to lead to emotional reaction and could be accompanied by an increase in energy metabolism. This increase was significant in both the control submissive and SRBC-treated dominate males. Thus, the modification of mice smell perception due to antigen injection can affect the pair-wise competition.