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Nasal aerodynamics protects brain and
lung from inhaled dust in subterranean
diggers, Ellobius talpinus
rspb.royalsocietypublishing.org
Research
M. P. Moshkin1,7,8, D. V. Petrovski1, A. E. Akulov1, A. V. Romashchenko1,5,
L. A. Gerlinskaya1, V. L. Ganimedov2, M. I. Muchnaya2, A. S. Sadovsky2,
I. V. Koptyug3, A. A. Savelov3, S. Yu Troitsky4, Y. M. Moshkn6,
V. I. Bukhtiyarov4, N. A. Kolchanov1,7, R. Z. Sagdeev3 and V. M. Fomin2
1
Institute of Cytology and Genetics, 2Khristianovich Institute of Theoretical and Applied Mechanics,
International Tomographic Center, 4Boreskov Institute of Catalysis, and 5Design Technological Institute of
Digital Techniques, Siberian Branch of RAS, Novosibirsk 630090, Russia
6
Department of Biochemistry, Erasmus Medical Center, Dr. Molewaterplein 50, Rotterdam 3015GE,
The Netherlands
7
Department of Physiology, Novosibirsk State University, Novosibirsk 630090, Russia
8
Department of Zoology and Animal Ecology, Tomsk State University, Tomsk 634050, Russia
3
Cite this article: Moshkin MP et al. 2014
Nasal aerodynamics protects brain and lung
from inhaled dust in subterranean diggers,
Ellobius talpinus. Proc. R. Soc. B 281:
20140919.
http://dx.doi.org/10.1098/rspb.2014.0919
Received: 17 April 2014
Accepted: 23 July 2014
Subject Areas:
ecology, biomechanics, physiology
Keywords:
subterranean rodents, adaptation to dust,
nanoparticles, nasal aerodynamics,
Ellobius, Mus
Author for correspondence:
M. P. Moshkin
e-mail: [email protected]
Electronic supplementary material is available
at http://dx.doi.org/10.1098/rspb.2014.0919 or
via http://rspb.royalsocietypublishing.org.
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.
1. Introduction
The life of subterranean fossorial rodents is associated with the constant digging
of tunnels [1] and, as a result, breathing in air with a high concentration of dust
particles. For digging, chisel-tooth-diggers use prominent teeth to loosen the soil
keeping their lips closed behind the teeth to prevent soil from entering the buccal
cavity [2]. In the process of digging, breathing takes place solely through the
nose, which provides an attractive surface for accumulation of solid air-dispersed
sub-micrometre and nano-sized particles inhaled from polluted air.
The particles deposited on olfactory epithelium can be transported into
olfactory bulbs and further into the brain [3]. Intranasal application or inhalation
of nano-sized and even sub-micrometre particles of titanium, silicon, iron and
manganese (Mn) oxides results in a significant increase of the studied elements
first in the olfactory bulbs and then in other parts of the brain of rats and mice
[4–6]. Accumulation of certain metal ions, for example manganese, and nanoparticles results in severe neurotoxic effects [6,7]. In case of nanoparticles, these
effects are independent of their chemical composition. For example, accumulation of seemingly neutral compounds, such as silicon and titanium oxide, in
the brain triggers the activation of free radical oxidation and the expression of
pro-inflammatory cytokines [5,8].
& 2014 The Author(s) Published by the Royal Society. All rights reserved.
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(a) Magnetic resonance imaging of the nasal cavity and
the creation of a three-dimensional model
Geometric parameters of the nasal cavities of the laboratory mice
(n ¼ 3) and the mole vole (n ¼ 3) were determined by MRI on
BioSpec 117/16 USR (Bruker, Germany, 11.7T). The final geometry of the nasal cavities was deduced from comparison of MRI
images with the rodent anatomical atlas [11] to account for
small bones (see the electronic supplementary material for
detailed description of the MRI study).
The shapes of the nose passages were modelled on the basis
of a series of tomograms in parallel sections, which were
obtained by MRI with a step size of 0.3 mm. A geometric
model of the nasal cavity was constructed using the GRAPHER
software system (Golden Software) and geometry software package GAMBIT. The procedure of construction is described in the
electronic supplementary material.
(b) Numerical modelling of the nasal airflow and
aerosol deposition in the nasal cavity
A steady-state air flow in nose passages in the breathing-in
regime was calculated with the use of the FLUENT 12 (ANSYS)
software system.
Incompressible Navier– Stokes equations were used to
describe the flow:
@ uj
¼0
@ xj
and r
@ (uj ui )
@ ui
@ p @ t^ ji
þr
¼
þ
:
@t
@ xj
@ xi @ xj
where Sij is the tensor of the strain rates
1 @ ui @ uj
Sij ¼
:
þ
2 @ xj @ xi
The no-slip conditions were imposed on the duct walls.
A pressure drop between the duct entrance and exit was
specified in the exit section; the value was negative in the case
of inhaling. The steady-state solution was found by a timedependent method, and the error was taken to be 1025. The
basic results were obtained on grids with the number of
volume cells equal to (3.0 – 4.0) 106. Some verification computations were performed on the finer meshes (see corresponding
section in the electronic supplementary material).
The computations estimate the distribution of the flow velocity vector at all points of the nasal cavity and allow
determination of the regions with the maximum velocity, the
stagnant zones where the flow velocity is close to zero and
reverse flow regions where the flow velocity is opposite to the
main flow direction. In addition, the air mass flow was calculated
for each value of the pressure drop.
In order to calculate the deposition of nanoparticles, uniform
injection of approximately 4000 particles per injection into the
nasal cavity was assumed. Particles that were 5 –500 nm in size
and had a material density of 1000 kg m23 were considered.
On the base of the program FLUENT 12, the setting up of a problem was as follows: the Navier – Stokes equations were used
for the motion of air, and the Lagrange approach was used to
track the particle trajectories.
(c) Transfer of manganese from the nasal cavity into
the brain
The study was conducted on six mice and six mole voles, with
three animals in each of the experimental groups. In order to
investigate the transfer of manganese ions and hydrated nanoparticles MnO . (H2O)x into the brain, MnCl2 and nanoparticles
were administered into the left nostril, under an urethane
anaesthesia (75 mg kg21), using an automatic pipette until the
nasal cavity was fully filled. The manganese-enhanced MRI
(MEMRI) of the olfactory bulbs was studied 24 h following
the intranasal administration on animals under isoflurane anaesthesia (SEP-10S PLUS, AitecsViltechmeda). See the electronic
supplementary material for detailed description of MEMRI.
(d) Comparative analysis of manganese accumulation
through inhalation of aerosols
The study was conducted on 10 mice of the inbred line C57BL/6
and 10 male mole voles. For the exposure to nano-aerosols, the
following set-up was created (electronic supplementary material,
figure S4a). The aerosol was created from 0.2 M MnCl2 solution
with an average droplet size of approximately 47 nm (electronic
supplementary material, figure S4b) pumped at the rate of
approximately 125 000 particles ml21. The resulting nano-aerosol
had comparable characteristics to that used in the aerodynamic
model with regard to the density approximately 1000 kg m23,
the droplet size and the lack of charge to prevent electrostatic
effects on particles transmission.
Accumulation of manganese in the olfactory bulbs was
studied using seven mice and seven mole voles, which were
2
Proc. R. Soc. B 281: 20140919
2. Material and methods
Here, t is the time, xi are the point coordinates in space, ui are
the velocity components, r is the density, p is the pressure and
m is the viscosity. The tensor of viscous stresses is calculated by
the following formula:
1 @ uk
t^ ji ¼ 2m Sij dij ,
3 @ xk
rspb.royalsocietypublishing.org
Fossorial animals inhabit environments with high concentrations of Mn and/or cadmium in soil [9] and are subjected
to elevated levels of dust. We wondered whether in these
animals the nasal aerodynamics could help the removal of
sub-micrometre and nano-sized solids from the inhaled air
before it reaches the lungs and olfactory epithelium. To test
this idea, we conducted a comparative study of the geometry
and the gas dynamics of the nasal cavities of species that
occupy two distinct ecological niches: terrestrial and subterranean. Laboratory mice, Mus musculus, of the inbred line
C57BL were used to represent aboveground rodents, whereas
the mole vole, Ellobius talpinus, exemplified the underground
fossorial lifestyle. The mole vole is a chisel-tooth-digger
inhabiting steppe, forest-steppe and semi-desert in Eastern
Europe, the Urals, Central Asia and southwest Siberia [10].
Both species are close in size allowing an adequate morphological comparison. First, we reconstructed the nasal cavities
of the mouse and the mole vole using magnetic resonance
imaging (MRI). Next, we performed comparative numerical simulations of intranasal flow of sub-micrometre and
nano-sized particles followed by MRI analysis of manganese
chloride (MnCl2) nano-aerosols and hydrated manganese
oxide (MnO . (H2O)x) nanoparticles transportation efficiency
from the nasal cavity to the brain. Collectively, these studies
uncovered species-specific differences in the nasal geometry
and aerodynamics, which in the mole vole lead to a reduced
accumulation of nano-sized aerosols on the surface of
olfactory epithelium and in the olfactory bulbs.
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(a)
mouse
max
(b)
mole vole
mouse
3
mole vole
rspb.royalsocietypublishing.org
L = 14.2 ± 0.9
L = 11.5 ± 0.5
(a' )
hmax =
7.3 ± 0.3
hmax =
4.6 ± 0.2
Wmax = 7.0 ± 0.3
(d) 2.00
mouse (100 pa)
mouse (150 pa)
mouse (200 pa)
mole vole (100 pa)
mole vole (150 pa)
mole vole (200 pa)
0.9
deposition fraction
0.8
0.7
0.6
0.5
0.4
0.3
0.16
0.14
0.12
0.10
0.08
0.06
0.2
0.04
0.1
0.02
0
1
10
100
d (nm)
1000
mouse (100 pa)
mouse (150 pa)
mouse (200 pa)
mole vole (100 pa)
mole vole (150 pa)
mole vole (200 pa)
0.18
deposition fraction
(c) 1.0
min
0
1
10
100
1000
d (nm)
Figure 1. Quantitative modelling of nasal aerodynamics and dust deposition in the mouse and the mole vole. (a) Three-dimensional models of the nasal cavities.
The ethmoid turbinate (ET) is outlined with a black line. (a 0 ) MRI slices of the maximum cross section (a, dashed line) of the nasal cavities and the quantitative
values (means + s.e.) for the maximum height (hmax), maximum width (Wmax) and length (L), derived from MRI scans of three mice and three mole voles.
Differences between mouse and mole vole are statistically significant for all dimensions ( p , 0.01, Mann –Whitney U-test). (b) The quantitative model of the
absolute velocities jVj, and (b0 ) streamline distribution in the nasal cavities of laboratory mice and mole voles. Cross section in the middle of the model (vertical
lines on (b0 )) revealed the following proportions of the upper/middle/low parts of air flow expressed as % from the total flow: 41.1/53.8/5.1 for mouse and 30.9/
42.5/26.6 for mole vole. (c) Fraction of particles deposited on the total surface of the nasal cavity in laboratory mice and mole voles, as a function of particle size
and respiratory pressure changes (Pa). (d ) Fraction of particles deposited on the surface of the olfactory epithelium (ET) in laboratory mice and mole voles, as a
function of particle size and respiratory pressure changes (Pa).
exposed to the aerosols for a period of 2 h. Three control mice
and three control mole voles were also placed in the exposure
chamber and provided with a manganese-free airborne mixture.
The accumulation of manganese in the olfactory bulbs was
detected by the MRI signal expressed in conventional units
(CU). See the electronic supplementary material for detailed
description of experimental procedures.
vole and 31 g for the mouse. For the mole vole, the values
of Sw and V were 515 mm2 and 60 ml, respectively, and for
the mouse these values were 219 mm2 and 17 ml, respectively.
V of the nasal cavity is a part of the ventilation dead space,
which according to power law is proportional to body mass
raised to power of 0.78 [12]. Thus, V per unit of body
mass0.78 was equal to 2.5 ml g21 in the mole vole and
1.2 ml g21 in the mouse.
3. Results
(a) Magnetic resonance imaging analysis and threedimensional modelling of the nasal cavity
The size and the shape of nasal cavities have pronounced
differences between species in the area of maximum cross
section (figure 1a), which is 1.13 + 0.10 mm2 in the mouse
and 3.33 + 0.25 mm2 in the mole vole ( p , 0.01, Mann –
Whitney U-test). All dimensional characteristics of the
nasal cavities of the mole vole surpassed that of the laboratory mouse (figure 1a0 ). For characterization of the total
surface area (Sw) and the volume (V ), the three-dimensional
reconstructions of the nasal cavities from MRI data were
obtained for an average body weight of 58 g for the mole
(b) Quantitative modelling of aerodynamics
Respiratory parameters, registered from conscious animals
(electronic supplementary material, figure S1), were used to
determine the boundary values of respiration for the quantitative modelling of aerodynamics of the nasal cavity. In mice,
tidal volume varied between 150 and 250 ml, with a respiratory rate of 170– 320 cycles per minute. In the mole vole, the
respiratory volume varied between 350 and 400 ml, and the
rate was found to be between 150 and 200 cycles per minute.
Because breathing through the oral cavity is insignificant
in rodents, the data from the plethysmography reflect the
volumes of air that enter the nasal cavity during inhalation
and exhalation. Based on these data, the average values of
Proc. R. Soc. B 281: 20140919
Wmax = 4.4 ± 0.4
(b')
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(a)
(b)
(c)
4
2.0
1.6
(b' )
CU
CU
1.4
1.3
MnO · (H2O)x
MnCl2
control
MnCl2
Figure 2. The accumulation of Mn in the olfactory bulbs of mice (grey bars) and mole voles (black bars) following the intranasal instillation of MnO . (H2O)x and
MnCl2 solutions or inhalation of nano-aerosols containing MnCl2. (a) Intensity of the MRI signal in CU in the olfactory bulbs in mice and mole voles 24 h after
intranasal application of the nanoparticles of MnO . (H2O)x and MnCl2 solutions. (b) MRI axial sections of the olfactory bulbs of mouse (b) and mole voles (b0 )
following 24 h inhalation of nano-aerosols containing MnCl2. (c) Intensity of the MRI signal (CU) in the olfactory bulbs of mice and mole voles in the control
group and in the group exposed to nano-aerosols containing MnCl2 24 h before MRI study. Double asterisk (**): mole voles accumulate significantly less Mn
in the bulbs from nano-aerosols than mice as revealed by Student t-test (t12 ¼ 3.76, p ¼ 0.003).
the airflow in the nasal cavities were determined to be
1.5 ml s21 for the mouse and 2.5 ml s21 for the mole vole.
These values correspond to a pressure difference of 175 Pa
for the mouse and 140 Pa for the mole vole. Thus, the main
results of the calculations are presented for the interval of
pressure drop from 100 to 200 Pa, which corresponds to a
normal respiratory rate for the studied animals.
Theoretical visualization of the airflow in the nasal cavity
and the flow characteristics are illustrated in figure 1b. In the
nasal cavity of mole vole, the flow is divided into three parts,
which are comparable in magnitude. Cross section in the
middle of the nasal model length revealed the following
proportions of the flows in the upper (30.9%), the middle
(42.5%) and the low parts (26.6%) of the total air flow. By contrast to mole vole, the two dominant flows were evident in
the cross section of mouse nasal cavity: the top—41.1%, the
middle—53.8% and the low—5.1% (figure 1b0 ).
The volume fraction of ethmoid turbinate (ET) in the mole
vole is higher than in the mouse, and airflow through this
part of the nasal cavity is very weak (figure 1b0 ). The theoretically predicted dependence of the volume flow rate on
respiratory effort indicates a lower resistance to the inhaled
air flow in the mole vole as compared with the mouse
(electronic supplementary material, figure S2).
(c) Quantitative modelling of aerosol deposition
in the nasal cavity
The deposition of differently sized particles was calculated for
the total surface area of the nasal cavity and for the surface of
the ET, which is the main location for olfactory epithelium
(figure 1a). The ET makes up 47.6% of the total surface area
in the mouse and 54.6% in the mole vole. These values are
in agreement with the data obtained during the analysis of
serial histological slices of the laboratory mice [13].
In both species, the deposition of the particles in various
regions of the nasal cavity is sharply reduced as the particle
size increases from 5 to 50 nm and remains practically
constant (very weak decreasing) after reaching 100 nm
(figure 1c). In addition, the amount of sub-micrometre particles
(greater than 50 nm) that are deposited on the total surface of
the nasal cavity is approximately 1.5 times higher in the mole
vole than in the mouse. However, on the surface of the ET,
the deposition is opposite. In the mouse, twice as many particles are deposited on the ET as compared with the mole
vole (figure 1d). In the mouse, the total deposition efficiency
decreases with an increase of the pressure drop from 100
to 200 Pa. A similar pattern was described for the rat [14]. In
the mole vole, total deposition has the same character for particles sized up to about 30 nm. But for greater size values,
particle deposition increases with increase of pressure drop
(or flow rate), suggesting that the structure of the mole vole
nasal cavity promotes an effect of particle inertia to a greater
extent. This effect is most likely owing to the differences in geometry of the nasal cavities for the mole vole and for the mouse
and the rat, which are similar among themselves.
(d) The uptake of Mn2þ ions and MnO . (H2O)x
nanoparticles from olfactory epithelium into
the brain
To study the transfer of Mn2þ and nanoparticles, we instilled
the solutions of MnCl2 or a suspension of MnO . (H2O)x into
the left nostril. Mn accumulation in the olfactory bulbs was
tested 24 h following the intranasal administrations by
means of the MEMRI. The quantitative correspondence
between the intensity of the MRI signal and the concentration
of Mn in the olfactory bulb was assessed in a separate study
on 12 mice (electronic supplementary material, figure S3).
CU of the MRI signal showed highly significant correlation
with the concentration of Mn in the studied brain tissue
(r ¼ 0.96, p ¼ 0.003).
A two-factor analysis of variance showed that the
intensity of the MRI signal (CU) in the olfactory
bulbs (figure 2a) is independent of the animal species
(F1,10 ¼ 0.001, p ¼ 0.98) and of the type of Mn administered
(F1,10 ¼ 0.03, p ¼ 0.88).
Proc. R. Soc. B 281: 20140919
1.2
1.2
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**
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4. Discussion
Numerical simulation of intranasal airflows based on the geometric differences of the nasal cavities revealed that in the nasal
cavities of the mouse, the air streaming through the dorsal
meatus predominates; while in the nasal cavity of the mole vole
the air streaming through the middle and ventral meatus prevails. The most obvious differences between the studied species
occur in the spatial organization of the Z-shaped caudal flow,
which directly hits the external surface of the ET in mouse and
rat [15], while a buffer region is created between the caudal
flow and the ET in the mole vole (figure 1b0 ).
The revealed differences in airflow organization result in
theoretically predicted differences in deposition of inhaled
aerosols in the studied species. The fraction of the particles
deposited on the total surface of the nose is 1.5 times larger
in the mole vole compared with the mouse, which corresponds to a greater than twofold difference in the surface
area of the nasal cavity. Another important aspect, which
was determined through quantitative modelling of the
deposition of aerosols is that with a large change in
pressure, which corresponds to forced breathing, the deposition of solid particles (more than 30 nm) increases in the
mole vole. It is in contrast with our calculations for the laboratory mouse and the data for the rat [14]. Both terrestrial
species show a decreasing deposition of solid particles with
an increasing flow rate. In the mole vole nose, the stream
after input section immediately expands and turns downward at an angle about twice as large than that of the
mouse and the rat promoting an effect of particle inertia.
In the input section, particles accelerate to high velocities
in the narrow and elongated space of the nasal entry.
Rapid turns deviate this flow significantly resulting in
large particles (more than 30 nm) depositing on the surface
by inertia, especially, under higher flow rates. This effect is
reflected by an instant dependence between flow and deposition rates in the mole vole, but not in the mouse, in which
the turn angle is smaller (figure 1b 0 ). For smaller particles
(less than 20 nm), however, inertia is low and the deposition
rate depends inversely on the flow rate with less effect from
the turn angle (figure 1c).
Animals were handled in compliance with the rules of the Animal
Care and Use Committee, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science, Novosibirsk, Russian
5
Proc. R. Soc. B 281: 20140919
The accumulation of Mn in the olfactory bulbs was investigated through MEMRI scans 24 h after a 2 h exposure of
mice and mole voles to chambers containing aerosols of
MnCl2 and chambers free of MnCl2 (control). The control animals of the investigated species did not vary in the intensity
of MRI signal (t ¼ 0.82, p ¼ 0.46). However, the intensity of the
MRI signal was significantly larger in laboratory mice exposed
to the MnCl2 aerosols (figure 2b,c), compared with the mole
voles exposed to the same condition (t ¼ 3.76, p ¼ 0.003).
To account for the effect of body size on accumulation of
Mn2þ ions from the inhaled aerosols, we performed an
additional experiment on Syrian hamsters. Syrian hamsters
are terrestrial rodents, whose body mass is approximately
two times higher than the mole vole’s. Intensity of MRI
signal in the olfactory bulb did not differ significantly from
the mouse, but exceeded significantly the signal observed for
the mole vole (electronic supplementary material, figure S5).
It is known that lung ventilation is determined by oxygen
consumption, which varies from minimal values during sleep
to maximum values during physical activity. In mice, the
highest activity is observed when the mouse leaves its nesting
chambers for ‘fresh air’ [16]. In fossorial rodents, represented
by the mole vole, the highest intensity of energy metabolism
and ventilation rate is observed during the process of digging
tunnels [17]. In the subterranean mole vole, the deposition of
sub-micrometre and nano-sized particles on the nasal epithelium is increased upon increase of respiratory rate,
which results in the lowering of solids accumulation in the
lower respiratory tract.
Despite the fact that the surface area of the ET in the mole
vole is 2.7 times larger than in the mouse, the fraction of aerosols that is deposited in this area is two times lower. As a
result, the total number of particles per square unit (mm2)
deposited on the surface of the olfactory epithelium is
approximately six times less in the mole vole than that in
the mouse. This condition can play a significant role in the
defence of the brain of subterranean rodents against potential
neurotoxic particles, which make up part of the inhaled aerosols. Our data show that both Mn2þ ions and MnO . (H2O)x
nanoparticles transfer efficiently from the olfactory epithelium into the bulbs and further into the brain in both
species upon direct intranasal instillation. However, when
Mn2þ ions were administered in the form of nano-sized aerosol (50 nm), the accumulation of Mn in the olfactory bulbs
was significantly lower in mole voles than in mice and Syrian
hamsters. Although the direct measurements of airflow for animals are nearly impossible, our numerical analysis of nasal
airflow in the mole vole and in the mouse provides a potential
mechanism to account for this species-specific difference. The
nasal cavity of the mole vole prompts higher deposition of
inhaled particles on the total surface of the cavity, which results
in a significant decrease in deposition of aerosols in the region
of the ET and their accumulation in olfactory bulbs. Thus, in
comparison to the mouse, the nasal structure of the mole
vole limits more effectively the transfer of dust particles into
the brain and the lungs.
Epidemiological observations suggest an ecological significance of the accumulation of certain metals, including
Mn, in brain structures. For example, deterioration in motor
function is proportional to the levels of Mn found in the
soil of various geochemical provinces [18]. Likewise, an
increase in Mn in the brains of professional welders leads
to a quicker development of Parkinson’s disease [19,20].
Negative effects of nano- and micro-sized aerosol inhalation
are not limited to the brain but also extend to lungs [21]. In
this regard, the nasal structure of the mole vole, as a representative of subterranean mammals, points to a possible
adaptive mechanism to habitation in an environment with
dust excess. We anticipate that this adaptation is not limited
to just one trait and that a complex of morphological and
functional properties serves to protect subterranean animals
from the exposure to nano- and sub-micrometre-sized aerosols. Therefore, a larger comparative study will be of
interest for future studies to elucidate adaptive patterns for
underground life under dust load.
rspb.royalsocietypublishing.org
(e) Accumulation of Mn2þ ions in the brain following
nano-aerosol exposure
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Federation (ICG SB RAS). All experimental procedures were
approved by the Bioethics Review Committee, ICG SB RAS.
integration research grants from the Siberian Branch of the
Russian Academy of Sciences (grant nos 57, 60, 61, 108 and
122) and by a grant of the Russian Science Foundation (grant
no. 14–14– 00221).
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Acknowledgements. We wish to thank Matvey Y. Moshkin and
L.I. Khlestova for extensive assistance in the preparation of this
manuscript and W. Lidicker for the helpful comments.
Funding statement. This study was supported by the Interdisciplinary