Extract
Note: Please read the complete
full text with Figures and Tables at
Introduction
Due to ubiquitous use in daily life, electromagnetic fields
(EMF) radiated by global system for mobile communications
(GSM) equipment have attracted attention as a potentially
hazardous environmental factor. Debates on whether GSM
microwaves may induce "non-thermal" effects on biological
tissues are increased. Epidemiological research has
indicated that the brain is likely to be affected by mobile
phones[1,2]. Numerous in vivo
and in vitro studies have been performed to investigate the biological consequences and to
assess the health risks of GSM microwaves on the nervous
system.
Until now, the results from the studies concerning the
effects of GSM on the nervous system were highly
controversial and failed to reveal an unequivocal correlation
between the use of mobile phones and brain function. However,
increasing studies indicate that mobile phones may affect
cognitive processes, as well as learning and memory. GSM
microwaves have been found to produce a significant
decrease in choice reaction time[3], slower response and
decision speed[4], and alters brain potential in humans
performing a visual monitoring
task[5,6]. Mobile phones have also been reported to induce a loss of mental regeneration and
impair cognitive performance[7,8]. The exposure of the left
side of the human brain to GSM microwaves was found to
slow down the left-hand response time, which was apparent
in 3 of the 4 distinct cognitive tasks, including spatial item
recognition, verbal item recognition, and 2 spatial
compatibility tasks[9]. A recent study also indicated that GSM-type
radiation could induce seizures in rats following their
facilitation by subconvulsive doses of picrotoxin
[10].
The potential influence of the radiation frequency (RF)
field on brain development has also been studied.
Treatment with 10 mW/cm2 of 2450 MHz microwave
radiation did not significantly affect the gross and histological
development of the rat brain[11]. Mice offspring irradiated in the
uterus with 2450 MHz RF radiation at a specific absorption
rate (SAR) of 0.4 W/kg did not produce significant
alterations in brain organogenesis, including weight of fetal brains
and brain RNA and DNA and protein
levels[12], while exposure at 28
mW/cm2 induced a lower brain
weight[13]. A study on the cerebella of Japanese quails whose eggs were
continuously exposed to 5.0 mW/cm2 of 2.45 GHz microwave
radiation showed a slight developmental retardation in the
cerebellar cortices[14]. An in vitro
investigation that studied the effects of GSM microwaves on synaptic function during
the development period revealed that GSM 1800 MHz
microwaves may reduce excitatory synaptic activity and the
number of excitatory synapses in cultured rat hippocampal
neurons[15]. Apparently, the conclusion can not be drawn yet
whether low level microwaves have biological effects on brain
development in animals. Furthermore, the cellular and
molecular mechanisms underlying the biological effects of
microwaves on brain function and development are still unclear.
The loss of excitatory drive on developing neurons with
adaptive changes in neuronal morphology and connectivity
has been proposed as a plausible mechanism involved in
behavioral alterations[16]. Thus, the morphological study on
developing neurons in vitro in living cells is preferred for
further investigating the cellular and molecular mechanisms
underlying the effects of microwaves on brain function.
In our experiments, we attempted to determine whether
and how exposure to GSM 1800 MHz microwaves at
different intensities during neuronal development from 6 days
in vitro (DIV6) to DIV14 interferes dendritic development in
cultured hippocampal neurons by living cell imaging on a
fluorescence microscope.
Materials and methods
Primary hippocampal neuronal cultures and neuronal
transfections Primary hippocampal cultures were prepared
based on the method described
previously[17]. Briefly, newborn rats (P0) were careful dissected, and then the
hippocampi were chopped and digested in 0.25% trypsin (Sigma, St
Louis, MO, USA) for 15 min at 37 oC with gentle shaking.
Dissociated cells were plated at a density of
5×105 cells/cm2 in a 35 mm dish (Nunc, Roskilde, Denmark) with
poly-L-lysine-coated coverslips in Dulbecco's modified Eagle's media
(Invitrogen, Carlsbad, CA, USA) containing 10% fetal
bovine serum (FBS) and 2 mmol/L glutamine, and maintained at
37 oC in a humidified atmosphere with 5%
CO2. After culturing in vitro for 24 h, the medium was replaced with
Neurobasal medium containing 2% B27 supplement, 1%
antibiotic, and 0.25% glutamine (Invitrogen, USA). At DIV5,
cytosine arabinofuranoside was added at a final
concentration of 10 µmol/L. Thereafter, half of the medium was
replac-ed twice a week with Neurobasal medium containing 2% B27
supplement, 1% antibiotic, and 0.25% glutamine.
Hippocampal neurons were routinely transfected with farnesylated
enhanced green fluorescent protein (F-GFP) and GFP-actin
by Lipofectamine 2000 (Invitrogen, USA) at
DIV5[17].
Microwave exposure The modulated microwave
exposure system was designed by the Foundation for
Information Technologies in Society (Zurich,
Switzerland)[18]. It mainly consists of a RF generator, an arbitrary function
generator, a narrow band amplifier, and 2 rectangular
wave-guides operating at a frequency of 1800 MHz. The 2
wave-guides, one for exposure and the other for sham exposure as
the control, were placed inside a conventional incubator to
ensure constant environmental conditions (37
oC, 5% CO2, 95% humidity). A dish holder inside the waveguide
guarantees that the dishes are placed exactly in the H field maximum
of a standing wave and exposed simultaneously in E
polarization inside a waveguide. The system enables the
exposure of a monolayer of cells with a non-uniformity of SAR of
less than 30%. Six Nunc dishes can be exposed
simultaneously in 1 exposure waveguide. The entire setup is
computer controlled, enabling the automated control of the
exposure parameters, including exposure strength (SAR) and
exposure time.
All experiments were performed with the GSM 1800 MHz
signals. The signal is an amplitude modulated by
rectangular pulses with a repetition frequency of 217 Hz and a duty
cycle of 1:8 (pulse width 0.576 ms) corresponding to the
dominant modulation component of GSM.
The system's temperature remained at 37±0.1
oC during the whole exposure duration, and the temperature between
the microwave-exposed and sham-exposed cultures never
exceeded 0.1 oC. Therefore, the results were observed under
a condition of no obvious temperature change.
Hippocampal neurons were exposed to the GSM 1800
MHz microwaves at 2.4 or 0.8 W/kg for 15 min/d from DIV6 to
DIV14.
Image processing and analysis The cultures were
maintained in a recording chamber in extracellular solution for
continuous perfusion. Nikon band pass filter cubes (Tokyo,
Japan) were used for detecting GFP. Living neurons
transfected with F-GFP and GFP-actin were imaged on a TE2000
inverted microscope (Nikon, Japan), equipped with 40×1.0
numerical aperture (N.A). objective lens. Digital images
were acquired with a charged couple device (CCD) camera
(CoolSNAP HQ, Roper Scientific, Tucson, AZ) controlled
with MetaMorph 5.0 software (Universal Imaging, West
Chester, PA, USA) capturing 200_2000 ms exposures. A single
level of focus was maintained throughout each recording.
Stacks were collected every 30 s. All images were captured
30 min after completing the last radiation of the GSM 1800
MHz microwaves.
When we imaged filopodia, 11 stacks for each neuron
were collected for measuring their mobility. Motility was
calculated as the absolute difference in length of
protrusions from frame to frame, divided by the total imaging time.
We defined filopodia in length as those whose length
exceeded 3 µm; filopodia in mobility was defined as those
extracting or retracting more than 0.8 µm/min, which were
defined as mobile filopodia in our study. The density of
filopodia was calculated based on the number of filopodia on all
secondary and third branches and their total length in a
neuron. The value is thus expressed as per 100 µm. The
mobility of filopodia was measured based on the percentage
of mobile filopodia in total filopodia more than 3 µm in length.
The lengths of all filopodia were manually traced and
measured with MetaMorph 5.0 (Universal Imaging Corporation,
USA).
Our length and motility measurements for filopodia are
likely to be slight underestimates of the actual values
because the z-axis projection partially obscures the true lengths
of filopodia going in and out of the final Z-plane. Motility
measurements would be further underestimated at early ages
by the fact that we did not take into account motility derived
from the bending, branching, or sweeping behavior of
filopodia.
For branches, we adopted the terminology used by
Havton and Ohara[19], which indicates that the dendrite
derived directly from the soma is the
first-order branch or primary dendrite, and the daughter branches arising from
primary dendrites are second-order branches, and so on. The
lengths of all dendritic branches were manually traced and
measured with MetaMorph 5.0.
For spines, we collected pictures with 40× magnification
so that all spines were displayed clearly. The density of
spines was calculated based on the number of spines on all
secondary and tertiary branches and their total length in a
neuron, and the value was expressed as per 100 µm.
The lengths of all dendritic filopodia and branches in
each picture were obtained by manually drawing skeleton
versions of the dendrites. The analysis was done blindly on
unprocessed images and there was no apparent variability
between the 2 observers (Wei NING and Shu-jun XU).
Filtering was used subsequently only for display purposes in
the final figures shown here. Data were from 3 independent
preparations of cell cultures and ensured independent
radiation procedures. Data were expressed as mean±SEM and
statistical significance was determined by ANOVA using SPSS
version 13.0 (SPSS, Chicago, IL, USA).
Results
GSM 1800 MHz microwaves decrease the density and
mobility of dendritic filopodia Dendritic filopodia of the
sham-exposed neurons were arranged with high density along
dendritic shafts (10.7±2.9/100 µm) and moved actively (85%
mobile filopodia; (Figures 1,2). In the neurons treated with
the chronic intermittent exposure of 2.4 W/kg GSM 1800
MHz microwaves from DIV6 to DIV8, the density of
dendritic filopodia significantly decreased by 38.9%±5.8%
(P<0.001, Figure 2A). To further evaluate the influence of the
GSM microwaves on the density of filopodia, we measured
the average number of mobile filopodia/100 µm dendrites by
analyzing the time-lapse images and obtained a similar result:
the density of mobile filopodia markedly decreased by
59%±4.1% (P<0.001, Figure 2B). In addition, the mobility of
filopodia (repre-sented by the percentage of mobile/total
filopodia) was reduced by 28%±6.0%
(P<0.001, Figure 2C) in the neurons exposed to GSM microwaves at a SAR of 2.4
W/kg. However, the average length of filopodia was
unaltered by microwave exposure (P>0.05, Figure 2D).
In contrast, the 0.8 W/kg GSM 1800 MHz microwave
exposure failed to induce any significant alteration in density,
mobility, or length of filopodia in the cultured hippocampal
neurons (P>0.05, Figure 2).
Mobile phone microwaves reduce the density of dendritic
spines It was previously reported that filopodia occurred
predominantly during the early development period of
neurons and metamorphose into
spines[20,21]. Since 2 important parameters of filopodia (density and mobility) were affected
by GSM microwaves, we observed whether those factors
would cause changes in the density of dendritic spines as a
consequence. The cultured neurons were exposed to GSM
microwaves 15 min daily from DIV6 to DIV9 and were
observed at DIV14. Concomitantly, the density of dendritic
spines showed an overall decrease of 14.3%±3.7%
(P<0.01, Figure 3C) in the neurons exposed to 2.4 W/kg GSM 1800
MHz microwaves. In addition, the spine density was not
affected by 0.8 W/kg GSM microwaves (Figure 3C).
GSM 1800 MHz microwaves cause different effects on
dendritic growth and arborization The exposure to GSM
1800 MHz microwaves at 2.4 W/kg for more than 5 d
decreased the total length of dendritic branches, but did not
change the arborization of dendritic trees, but the 0.8
W/kg microwave exposure did not alter both the growth and
arborization of dendritic trees (Figure 4). After exposure to
2.4 W/kg microwaves for 5 d (at DIV10) and 9 d (at DIV14),
the total length of the neurons was reduced by 19.6%±4.6%
and 18.9%±3.4%, respectively (P<0.05, Figure 4A), while no
change was observed after 15 min daily exposure for 3 d (at
DIV8). To examine the influence of 2.4 W/kg microwave
treatment on the growth and branching of dendritic arbors in
detail, we chose the neurons at DIV14 for further analysis,
because neurons at this age have passed the crucial
developmental period and have acquired their mature characters.
For each order of the dendritic arbors, we plotted the number
and the average length of dendritic branches (Figure 4C,
4D). For all the dendritic orders, the average segment length
in the exposed neurons was shorter than the sham-exposed
neurons, while the number of dendritic branches for most
dendrites did not change after exposure.
Discussion
This study demonstrates that chronic 2.4 W/kg GSM 1800
MHz microwave exposure is able to induce: (1) a significant
reduction in the density and mobility of dendritic filopodia;
(2) a notable decrease in the density of dendritic spines; and
(3) a decline in the segment length of dendrites, whereas the
0.8 W/kg microwaves do not show similar influences on
dendritic development in the cultured hippocampal neurons of
rats.
Our primary finding is that chronic 2.4 W/kg GSM
microwave exposure reduces the density and mobility of dendritic
filopodia. Dendritic filopodia, long and thin protrusions that
occur predominantly during early development of the
mammalian central nervous system, are thought to be
responsible for the formation of
spines[20_22]. Rapid extensions and movements of filopodia were described as a necessary step
for neurons to find new contact sites that can then evolve
into nascent synapses and mature into functional synaptic
connections[23,24]. Thus, the decrease in the density and
mobility of dendritic filopodia induced by microwaves may
affect the procedure resulting in the decreased formation of
mature synapses.
Consistently, our study shows that the density of spines
is decreased after 9 d exposure for 15 min/d. The result was
validated by another experiment conducted by our group
indicating that post synaptic density (PSD95) clusters were
reduced after the 2.4 W/kg GSM microwave
exposure[15]. Generally, the spines increase the surface area of dendrites,
the excitatory synaptic density, and the number
of connections between
neurons[25], and vice versa. Given the
decreased total length of dendritic branches, the absolute
number of excitatory synapses per neuron should be much less
than that reflected by the reduction of spine density. The
hippocampus is one of the most plastic parts of the adult
mammalian brain[26,27], and hippocampal changes, including
fluctuations in dendritic complexity, spine density, and soma
size may be associated with altered learning and memory
performance[28]. In rats, spine density of the dentate gyrus
and cornu ammonis fields CA1 region of the hippocampus
has been positively correlated with
water-maze learning and memory
performance[29,30]. Therefore, the density of
hippocampal spines may be an indication
of the efficiency of the synaptic network involved in
spatial learning and memory, and the microwave-induced alterations in dendritic
development and synaptic formation might have a potential
influence on animal behavior.
Interestingly, we observed that the growth of dendrites
was affected by the 2.4 W/kg GSM microwave exposure,
while dendritic branching was unaffected. There have been
numerous studies that have found that most intracellular
and extracellular factors affected dendritic growth and
branching simultaneously[31-33], while our results showed that they
were not necessarily affected at the same time by a certain
factor. Our study suggests that dendritic growth and
branching may be associated with different molecular motors or
second-messenger cascades[34]. Consistent with our finding,
Jones et al found that Abl tyrosine kinase activation
promoted both dendritic branching and growth, while
affecting dendritic branching more than its
elongation[35]. The complex and highly branched architecture of the dendritic
arbor is an important determinant of how a neuron accepts,
receives, integrates, and transmits inputs from other neurons.
A decrease in dendrite length might be sufficient to impair
intercellular signal transmission, change local circuit function,
and further influence connectivity patterns between brain
regions, leading to developmental and behavioral
disorders[36].
The alterations of dendritic growth and development
induced by GSM microwave treatment may be associated with
the changes in cytoskeleton_related molecules, such as actin
and microtubule-associated protein-2 (MAP-2). Mobile
phone radiation was found to affect the stability of F-actin
stress fibers[37] and increase the expression of the F-actin in
human endothelial cells[38,39]. The expression of MAP-2 in
hippocampal neurons was reported to decrease after
sustained exposure to static magnetic
fields[40]. Actin is highly enriched in dendritic
spines[41,42] and dendritic filopodia, and
its assembly is important for filopodial extension and
retraction[43]. MAP-2 is a major constituent of crossbridges
between microtubules in dendrites and is essential for growth
through the selective stabilization of dendritic microtubules[44], thus, these 2 molecules could be candidates of
targeting proteins that mediate the effects of GSM microwaves
on neurons. It would be interesting to further investigate
the underlying molecular mechanisms, such as identifying
other associated proteins and changes of the upstream
signal pathway.
In our study, all changes occurred at a relatively low
intensity and appeared time dependent, which may reflect
the non-thermal and accumulative effects of GSM
microwaves on dendritic development in cultured hippocampal
neurons. However, the direct transposition of our results to
mobile phone users is difficult to achieve since our
experiments were performed in the cultured hippocampal neurons
of rats. Therefore, the non-thermal effects of microwaves on
filopodia and branch development in cultured neurons in
our study may suggest its possible influence on the brain
and may be considered a potential health hazard of mobile
phones. The results derived from this in vitro
study need to be confirmed by future in vivo
studies. This study provides insights for further understanding some basic questions in
neuroscience, as well as molecular and cellular mechanisms
of GSM microwaves on learning and memory.
Acknowledgement
We are grateful to De-qiang LU and Guang-di CHEN for
help with the operation and maintenance of the exposure
apparatus.
References
1 Leventhal A, Karsenty E, Sadetzki S. Cellular phones and public
health. Harefuah 2004; 143: 614_20.
2 Santini R, Santini P, Danze JM, Le Ruz P, Seigne M.
Investigation on the health of people living near mobile telephone relay
stations: I/Incidence according to distance and sex. Pathol Biol
2002; 50: 369_73.
3 Preece AW, Iwi G, Davies-Smith A, Wesnes K, Butler S, Lim E,
et al. Effect of a 915 MHz simulated mobile phone signal on
cognitive function in man. Int J Radiat Biol 1999; 75: 447_56.
4 Hladky A, Musil J, Roth Z, Urban P, Blazkova V. Acute effects
of using a mobile phone on CNS functions. Cent Eur J Public
Health 1999; 7: 165_7.
5 Eulitz C, Ullsperger P, Freude G, Elbert T. Mobile phones
modulate response patterns of human brain activity. Neuroreport
1998; 9: 3229_32.
6 Freude G, Ullsperger P, Eggert S, Ruppe I. Effects of microwaves
emitted by cellular phones on slow brain potentials.
Bioelectro-magnetics 1998; 19: 384_7.
7 Maier R. Is CNS activity modified by pulsed electromagnetic
fields? Biomed Tech (Berl) 2001; 46: 18_23.
8 Maier R, Greter SE, Maier N. Effects of pulsed electromagnetic
fields on cognitive processes ¡ª a pilot study on pulsed field
interference with cognitive regeneration. Acta Neurol Scand
2004; 110: 46_52.
9 Eliyahu I, Luria R, Hareuveny R, Margaliot M, Meiran N, Shani
G. Effects of radiofrequency radiation emitted by cellular
telephones on the cognitive functions of humans. Bioelectromagnetics
2006; 27: 119_26.
10 Lopez-Martin E, Relova-Quinteiro JL, Gallego-Gomez R,
Peleteiro-Fernandez M, Jorge-Barreiro FJ, Ares-Pena FJ. GSM
radiation triggers seizures and increases cerebral c-Fos positivity
in rats pretreated with subconvulsive doses of picrotoxin. Neurosci
Lett 2006; 398: 139_44.
11 Inouye M, Galvin MJ, McRee DI. Effect of 2,450 MHz
microwave radiation on the development of the rat brain. Teratology
1983; 28: 413_9.
12 Merritt JH, Hardy KA, Chamness AF. In utero exposure to
microwave radiation and rat brain development. Bioelectromagnetics
1984; 5: 315_22.
13 Berman E, Carter HB, House D. Growth and development of
mice offspring after irradiation in utero with
2,450-MHz microwaves. Teratology 1984; 30: 393_402.
14 Inouye M, Galvin MJ, McRee DI. Effects of 2.45 GHz
microwave radiation on the development of Japanese quail cerebellum.
Teratology 1982; 25: 115_21.
15 Xu SJ, Ning W, Xu ZP, Zhou SY, Chiang H, Luo JH. Chronic
exposure to GSM 1800-MHz microwaves reduces excitatory
synaptic activity in cultured hippocampal neurons. Neurosci Lett 2006;
398: 253_7.
16 Kolb B, Forgie M, Gibb R, Gorny G, Rowntree S. Age, experience
and the changing brain. Neurosci Biobehav Rev 1998; 22:
143_59.
17 Luo JH, Fu ZY, Losi G, Kim BG, Prybylowski K, Vissel
B, et al. Functional expression of distinct NMDA channel subunits tagged
with green fluorescent protein in hippocampal neurons in culture.
Neuropharmacology 2002; 42: 306_18.
18 Schonborn F, Pokovic K, Burkhardt M, Kuster N. Basis for
optimization of in vitro exposure apparatus for health hazard
evaluations of mobile communications. Bioelectromagnetics
2001; 22: 547_59.
19 Havton LA, Ohara PT. Quantitative analyses of intracellularly
characterized and labeled thalamocortical projection neurons in
the ventrobasal complex of primates. J Comp neurol 1993; 336:
135_50.
20 Dailey ME, Smith SJ. The dynamics of dendritic structure in
developing hippocampal slices. J Neurosci 1996; 16: 2983_94.
21 Ziv N, Smith S. Evidence for a role of dendritic filopodia in
synaptogenesis and spine formation. Neuron 1996; 17: 91_102.
22 Fischer M, Kaech S, Knutti D, Matus A. Rapid actin-based
plasticity in dendritic spines. Neuron 1998; 20: 847_54.
23 Jontes D, Smith SJ. Filopodia, spines, and the generation of
synaptic diversity. Neuron 2000; 27: 11_4.
24 Vaughn JE. Fine structure of synaptogenesis in the vertebrate
central nervous system. Synapse 1989; 3: 255_85.
25 Sorra KE, Harris KM. Overview on the structure, composition,
function, development, and plasticity of hippocampal dendritic
spines. Hippocampus 2000; 10: 501_11.
26 Breedlove SM, Jordan CL. The increasingly plastic,
hormone-responsive adult brain. Proc Natl Acad Sci USA 2001; 98: 2956_7.
27 McEwen BS. Stress and hippocampal plasticity. Annu Rev
Neurosci 1999; 22: 105_22.
28 Woolley CS. Estrogen-mediated structural and functional
synaptic plasticity in the female rat hippocampus. Horm Behav 1998;
34: 140_8.
29 Nylund R, Leszczynski D. Proteomics analysis of human
endothelial cell line EA.hy926 after exposure to GSM 900 radiation.
Proteomics 2004; 4: 1359_65.
30 Pyter LM, Reader BF, Nelson RJ. Short photoperiods impair
spatial learning and alter hippocampal dendritic morphology in
adult male white-footed mice (Peromyscus
leucopus). J Neurosci 2005; 25: 4521_6.
31 Rajan I, Cline HT. Glutamate receptor activity is required for
normal development of tectal cell dendrites in
vivo. J Neurosci 1998; 18: 7836_46.
32 Redmond L, Kashani AH, Ghosh A. Calcium regulation of
dendritic growth via CaM kinase IV and CREB-mediated transcription.
Neuron 2002; 34: 999_1010.
33 Rosso SB, Sussman D, Wynshaw-Boris A, Salinas PC. Wnt
signaling through Dishevelled, Rac and JNK regulates dendritic
development. Nat Neurosci 2005; 8: 34_42.
34 Portera-Cailliau C, Pan DT, Yuste R. Activity-regulated
dynamic behavior of early dendritic protrusions: evidence for
different types of dendritic filopodia. J Neurosci 2003; 23:
7129_42.
35 Jones SB, Lu HY, Lu Q. Abl tyrosine kinase promotes
dendro-genesis by inducing actin cytoskeletal rearrangements in
cooperation with Rho family small GTPases in hippocampal neurons.
J Neurosci 2004; 24: 8510_21.
36 Miller JP, Jacobs GA. Relationships between neuronal structure
and function. J Exp Biol 1984; 112: 129_45.
37 Leszczynski D, Joenvaara S, Reivinen J, Kuokka R.
Non-thermal activation of the hsp27/p38MAPK stress pathway by
mobile phone radiation in human endothelial cells: molecular
mechanism for cancer- and blood_brain barrier-related effects.
Differentiation 2002; 70: 120_9.
38 Leszczynski D, Nylund R, Joenvaara S, Reivinen J. Applicability
of discovery science approach to determine biological effects of
mobile phone radiation. Proteomics 2004; 4: 426_31.
39 Ohara PT, Havton LA. Dendritic architecture of rat
somatosensory thalamocortical projection neurons. J Comp Neurol 1994;
341: 159_71.
40 Hirai T, Yoneda Y. Functional alterations in immature cultured
rat hippocampal neurons after sustained exposure to static
magnetic fields. J Neurosci Res 2004; 75: 230_40.
41 Caceres A, Payne MR, Binder LI, Steward O.
Immunocytochemical localization of actin and microtubule-associated protein
MAP2 in dendritic spines. Proc Natl Acad Sci USA 1983; 80:
1738_42.
42 Landis D, Reese T. Cytoplasmic organization in cerebellar
dendritic spines. J Cell Biol 1983; 97: 1169_78.
43 Sheetz MP, Wayne DB, Pearlman AL. Extension of filopodia by
motor-dependent actin assembly. Cell Motil Cytoskeleton 1992;
22: 160_9.
44 Harada A, Teng J, Takei Y, Oguchi K, Hirokawa N. MAP2 is
required for dendrite elongation, PKA anchoring in dendrites, a
proper PKA signal transduction. J Cell Biol 2002; 158: 541_9.
|
