Stress by Noise Produces Differential Effects on the Proliferation Rate of Radial Astrocytes

8/12/2019 Stress by Noise Produces Differential Effects on the Proliferation Rate of Radial Astrocytes

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Neuroscience Research 70 (2011) 243–250

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Stress by noise produces differential effects on the proliferation rate of radialastrocytes and survival of neuroblasts in the adult subgranular zone

Oscar Gonzalez-Perez a , b ,∗, Oscar Chavez-Casillas a , Fernando Jauregui-Huerta b , Veronica Lopez-Virgen a , Jorge Guzman-Muniz a , Norma Moy-Lopez a , Rocio E. Gonzalez-Castaneda b , Sonia Luquin b

a Laboratory of Neuroscience, Facultad de Psicologia, University of Colima, Colima 28040, Mexicob Department of Neuroscience, Centro Universitario de Ciencias de la Salud, University of Guadalajara, Guadalajara, Jal 44340, Mexico

a r t i c l e i n f o

Article history:Received 12 January 2011Received in revised form 28 March 2011Accepted 31 March 2011Available online 15 April 2011

Keywords:GlucocorticoidStressDentate gyrusNeural stem cellsSubgranular zoneGlial brillary acidic protein

a b s t r a c t

The subgranular zone (SGZ) in the dentate gyrus contains radial astrocytes, known as Type-1 or Type-Bcells , which generate neuroblasts ( Type-2 cells or Type-D cells ) that give rise to granular neurons. Stressincreasesglucocorticoidlevels thattarget SGZandmodify theproliferation andapoptosisof hippocampalcells. Yet, it is not well-known whether stress differentially affects SGZ progenitors. We investigated theeffects of noise-induced stress on the rate of proliferation and apoptosis of the Type-1 cells, Type-2 cellsand newly generated granular neurons in theSGZ. We exposed Balb/C mice to noise using a standardizedrodents’ audiogram-tted adaptationof a human noisyenvironment.We measuredcorticosteroneserumlevelsat differenttime points. Animals received BrdU injections for 3 days andsequential sacricesweredone to carry out double-immunohistochemical analyses. We found that a 24-h noise exposure did notproduce adaptative response in the curve of corticosterone as compared to a 12-h noise exposure. Thepercentage of BrdU+/GFAP+ cells was signicantly reduced in the stress group as compared to controls.A high proportion of CASP-3+/GFAP+ radial astrocytes were found in the stress group. The percentage of

BrdU+/doublecortin+cellswas higher in controls thanin thestressgroup.Interestingly, theapoptosisrateof doublecortin-expressing cells in the stress group was slightly lesser than in controls. Remarkably, wedid not nd signicant differences in the number of BrdU+/NeuN+ and CASP-3+/NeuN+ neurons. Thesedata indicate that stress differentially affects the rate of proliferation and apoptosis in SGZ progenitorsand suggest a possible compensatory mechanism to keep the net number of granular neurons.

© 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

1. Introduction

Neurogenesis in vivo has been demonstrated only in discreteregions of the adult brain: the subventricular zone and the sub-granular zone (SGZ). The source of new neurons in the adult brainis adult neural stem cells, which are multipotent and selfrenew-ing throughout life. The SGZ of the dentate gyrus is a proliferativeregion in the hippocampus that contains neuronal progenitors,which origin granular neurons. Approximately, 250,000 new neu-rons born in the adult SGZ per month ( Cameron and McKay, 2001 ).The primary progenitors of this region are radial astrocytes, knownas Type-1 cells or Type-B cells , that asymmetrically divideto give riseto neuroblasts also called Type-2 or Type-D cells (Seri et al., 2001;Zhao et al., 2008 ), which differentiate into granular neurons ( Seriet al., 2004; Seri et al., 2001 ).

∗ Corresponding author at: Laboratory of Neuroscience, Facultad de Psicologia,Universidad de Colima, Av. Universidad 333, Colima, COL 28040, Mexico.Tel.: +52 312 316 1091; fax: +52 312 316 1091.

E-mail addresses: [email protected] , [email protected] (O. Gonzalez-Perez).

There are a number of factors that may affect the hippocam-pal neurogenesis, such as: hormones ( Gould et al., 1992; Gouldand Tanapat, 1999 ), neurotransmitters ( Brezun and Daszuta, 1999;Gould et al., 1994 ), enriched environments ( Ramirez-Rodriguezet al., 2009 ), exercise ( van Praag et al., 1999 ), alcohol ( Cadete-Leite et al., 1988; Herrera et al., 2003 ), seizures ( Parent et al.,1997 ), and others ( Garcia-Fuster et al., 2010; Kong et al., 2010;Ramirez-Rodriguez et al., 2009; Yoshinaga et al., 2010 ). Recent evi-dence indicates that glucocorticoids reduce the proliferation rateof SGZ precursors ( de Kloet et al., 2008; Gould et al., 2000 ). Stress-ing conditions activate the HPA axis increasing the serum levels of glucocorticoids, which activate hippocampal glucocorticoid recep-tor ( de Kloet, 2003; De Kloet et al., 1993; de Kloet et al., 1999 ).Activation of GR under stressing conditions has been associatedwith a decrease on hippocampal neurogenesis, dendritic atrophy(Magarinos and McEwen, 1995 ), reduction in cell survival ( Joelset al., 2004;Ramos-Remuset al., 2002 ) andcell adhesion molecules(Sandi, 2003 ), and loss of excitatory synapses ( Zschocke et al.,2005 ). Nevertheless, little is known about the specic cell type inthe dentate gyrus that is predominantly affected by stressors. Inthis study, we investigated the effects of a noise-induced stress on

0168-0102/$ – see front matter © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.doi: 10.1016/j.neures.2011.03.013




244 O. Gonzalez-Perez et al. / Neuroscience Research 70 (2011) 243–250

the proliferation/apoptosis rate of the neuronal progenitors in theSGZ. We found that stress reduced the proliferation of the Type-1andType-2 cells, and increased the apoptosis of Type-1 cells. Inter-estingly, these changes do not appear to affect the number of newgranular neurons. These ndings suggest the existence of a possi-ble counterregulatory mechanism that compensates the initial low

proliferative rate induced by noise-induced stress.

2. Material and methods

2.1. Animals

We used 45-day-old Balb/C male mice housed in standard poly-carbonate cages (4 animals per cage) and maintained on a 12-hlight-dark cycle andwere allowed free accessto food andtap water.Twogroups were assembled( n = 35per group), a control group washousedunder standard biotery conditions andthe stress group wasexposed to a noisy environment as described below. All animalprocedures followed the guidelines of the Committee on AnimalResearch at the University of Colima.

2.2. Noise exposure

Stress by noise exposure was performed as described previ-ously ( Rabat et al., 2004; Rabat et al., 2005 ) and using the rodents’audiogram-tted adaptation of noisy environments donated by Dr.Rabat. Briey, acoustic adaptations of a noisy environment (i.e., thenoise of a French aircraft carrier boat) were done using the audiosoftware Wave lab 3.0 (Steinberg, Germany) that enabled to trans-late all frequencies of the noise from the human audiogram to thatof the mouse ( Rabat et al., 2004 ). This allows animals to betterdetect high (over 8000Hz) frequencies, which are more relevantto the auditory capacities of rodents ( Rabat et al., 2004 ). Then, micewere exposed to a sound containing random and unpredictablenoisy events for10 days. The intervalsof noise oscillated from 18 to39s followed by silent intervals ranging from 20 to 165s. Animalswere housed in a sound-isolated acoustic room adapted with pro-fessional tweeters (Steren Mexico 80-1088) and connected to anamplier (Mackie M1400; freq. 20 Hz–70 kHz; 300W, 8 ) mixer

software that delivered acoustic signals at levels of 70 dB for thebackground noise and from 85 to 103dB for the noisy events.

2.3. Corticosterone (CORT) assay

To quantify serum levels of CORT, mice ( n = 3 per time point

by each group) were decapitated and their blood was collected innon-heparinized tubes. Serum CORT levels were measured usingan enzyme immunoassay kit (Correlate-EIA. Assay Designs Inc.,USA), following the step-by-step protocol of manufacturer. In orderto avoid circadian variation, blood samples were obtained alwaysbetween 7:00 and 8:00 A.M.

2.4. Bromodeoxiuridine (BrdU) administration

BrdU is an analogous of tymidine that incorporates into DNAduring cell division ( Falconer and Galea, 2003 ). A day after thenoise-induced stress, we administrated 100mg/kg i.p. BrdU every12h ( Cameron and McKay, 2001 ), which were injected at 7:00hand 19:00h for 3 days. To label all progeny derived from the pri-

mary SGZ precursors, BrdU was injected from day 2 to day 4 andsacrices were done at day 4, 14 and 21 ( Fig. 1)

2.5. Tissue processing

Micewere sacricedbyan overdose of pentobarbital (100mg/kgbody weight) before transcardial perfusion. For uorescentmicroscopy ( n = 4 per group), mice were perfused with 0.9% NaClsolution at 37 ◦ C followed by 4% paraformaldehyde in 0.1M phos-phate buffer, and the brains were post-xed overnight at 4 ◦ C inthe same xative. 40- m thick coronal sections were cut with avibratome from − 1.70mm to − 2.54 mm Bregma coordinates. Flu-orescent immunostainings were performed as described below.

2.6. Immunohistochemistry (IHC)

Samples were rinsed (10 min × 3) in 0.1M buffer phosphatebuffer saline (PBS). Sections were then incubated in pre-warmed2N HCl at 37 ◦ C for 30min. Then, a single wash with 0.1 Mborate buffer (pH=8.4) for 10min was used to neutralize HCl.

Fig. 1. Differentiation process in the SGZ and the experimental design. On the top: schematic drawing illustrating the differentiation process in the SGZ. Type-1 radialastrocytes self-renew and giverise to Type-2 cells(doublecortin-expressing neuroblasts), whichin turnproliferate and differentiate intoNeuN-expressinggranular neurons.At bottom: experimental time line showing the 3-day injection of BrdU and sequential sacrices at day 4 (A), day 14 (B) and day 21 (4) after noise exposure.




O. Gonzalez-Perez et al. / Neuroscience Research 70 (2011) 243–250 245

After blocking in 0.1M PBS+ 10% normal goat serum for 1 h atroom temperature, samples were incubated with primary anti-bodies overnight at 4 ◦ C in blocking solution + 0.1% Triton-X. Thefollowing primary antibodies were used: mouse IgG anti-GFAP(1:500; Millipore), mouse IgG anti-NeuN (1:500; Millipore), mouseanti-Caspase3 active (1:800; Imgenex IMG-144A), rabbit IgG anti-

doublecortin (DCX) (1:500; Millipore) and rat anti-BrdU antibody(1:100; Accurate Chemical OBT0030). After that, tissue sectionswere rinsed three times with 0.1M PBS, incubated with theappropriateAlexaFluor ® conjugatedsecondary antibodies(1:1000;MolecularProbes)dissolved in blocking solution for60 minat roomtemperature, and washed three times in 0.1 M PBS. Nuclear coun-terstaining was done with 4 -6-diamidino-2-phenylindole (DAPI).

2.7. Quantication

To quantify the number of double-labeled cells, we analyzed atleast ten 40- m sections randomly selected, 120- m apart ( n = 4animals per group). Double-labeling was conrmed and quanti-ed by all matching cellular morphologies with clearly discernible

nuclei (DAPI+) and by analyzing non-overlapping high-power(40 × ) elds of view. For imaging, a Leica SP-2laser scanning confo-cal microscope was used and optical 0.75 m serial sections wereobtained to co-localize signals. For every section, the percentageof co-localization of BrdU+ cells was calculated as the fractionof the number of BrdU+ cells that co-expressed NeuN, DCX orGFAP/the total number of BrdU+ cells per section multiplied by100. A similar mathematical approach was used to calculate theproportion of CASP-3+ cells for each cell type. Data are expressedas mean ± standard deviation. For comparisons of means betweengroups, we usedthe Mann–Whitney“ U” test.Inallcases,the P <0.05value was chosen to establish signicant differences.

3. Results

3.1. Analysis of CORT serum levels

To determinethe stronger effects of noise on CORT serum levels,we assembled two groups: one group received a 12-h exposure tonoise followed by 12-h without noise for 10 days. The other groupwas exposed to incessantly noise for 24h per 10 days. Throughoutthe noise exposure, blood samples were collected by decapitatinganimals ( n = 3 per group)atdays 1,2,3, 5,7 and 10, and CORTserumlevels were measured. To obtain the basal line of CORT serum lev-els, we sacrice animals that were not exposed to noise. We foundthat, in the group of 12-h noise exposure, CORT levels increased atthe beginning of the stress induction but, at the day 7, CORT lev-els started to decrease ( Fig. 2). In contrast, the group of 24-h noiseexposure showed a progressive and steady increase in the CORTserum levels. This suggests that animals exposed to a continualnoise cannot adapt to this stressor. Therefore we chose the 24-hnoise exposure as the stress group to continue with the study.

3.2. Effect of stress on radial astrocytes cells in the SGZ

To determine the effects of stress on proliferation of astro-cytic neuronal precursors in the dentate gyrus, we sacricedanimals ( n = 4 per group) immediately after the noise exposureat day 4 ( Fig. 1) and immunostained brain sections with anti-BrdU and anti-GFAP antibodies. The proportion of BrdU+ cellsthat co-express GFAP was then calculated as described above.We found that the stress group showed a signicant reductionin the percentage of BrdU+ that co-express GFAP+ cells (25 ± 5%;P < 0.05, Mann–Whitney “ U” test) as compared to the control group(57 ± 8%) (Fig. 3). Since a reduction in the number of immunos-tained cells may be associated with changes in apoptosis rate, we

Fig. 2. Corticosterone serum levels during environmental noise exposures. Twoexperimental conditions were assessed: 12-h noise exposure and 24-h noise expo-sure for10 days.The groupexposedto 12-hnoiseexposure showeda rapid increasein corticosterone levels that decreased signicantly by day 7. In contrast, the groupexposed to incessant noise showed a persistent increase in corticosterone serumlevels.

quantied the number of cells that expressed Caspase-3-active

(CASP-3). Interestingly, the number of CASP-3+ cells was signi-cantly higher in the stress group (16 ± 2%; P < 0.05, Mann–Whitney“U” test) as compared to controls (4.4 ± 2%). These ndings showedthat stress reduced the number of proliferative radial SGZ astro-cytes, which coincided with a high apoptosis rate in this cellpopulation.

3.3. Effect of stress on Type-2 cells in the SGZ

Next, we investigated whether stress by noise modied thesurvival and apoptosis of Type-2 cells (SGZ neuroblasts) derivedfrom the Type-1 primary precursors pre-labeled with BrdU at day4 ( Fig. 1). Thus, we sacriced animals ( n = 4 per group)immediatelyafter the noise exposure at day 14. The stress group showed a sig-nicant reduction in the percentage of BrdU+/DCX+ cells (56 ± 5%;P < 0.01, Mann–Whitney“ U” test) as compared to controls (71 ± 8%)(Fig. 4). The proportion of CASP-3+ cells was slightly higher,but not statistically signicant, in the control group (18 ± 3%;P = 0.095, Mann–Whitney “ U” test) as compared to the stress group(11.8 ± 2%). These ndings indicated that stress reduced the num-ber of BrdU+ Type-2 cells, but did not show statistically signicantdifferences in apoptosis rate.

3.4. Effect of stress on granular neurons in the SGZ

Finally, we investigated whether stress by noise modied thesurvival and apoptosis of granular neurons in the SGZderived fromthe BrdU-labeled Type-1 cells at day 4. Animals were sacriced(n = 4 per group) immediately after the noise exposure at day 21.Interestingly, we did not nd statistically signicant differencesbetween the stress group in the number of BrdU+/NeuN+ cells(59 ± 10%; P = 0.34, Mann–Whitney “ U” test) as compared to con-trols(53 ± 7%)(Fig.5). We didnot ndstatisticallysignicantdiffer-ences in the number of CASP-3+ cells between the studied groups:the control group (7.7 ± 1.8%) and the stress group (6.8 ± 2.1%).Taken together, these results suggest that the noise-induced stressreduces thenumber of primary andintermediate progenitors in theSGZ, but has no signicant effect on mature granular neurons.

4. Discussion

Here we show that a 24-h noise exposure to environmentalnoise induces a signicant increase in CORT serum levels. With thisincessantnoise exposure as a stressmodel, we found that: (1)CORTlevels remain increased while the noise is present; (2) the prolif-eration of radial astrocytes in the SGZ of dentate gyrus is reduced





Fig. 3. Noise effects on Type-1 radial astrocytes. Immunostaining for GFAP and BrdU (A – B) and GFAP/CASP-3 (C–D) in controls and the stress group. The percentage of BrdU+ cellsthat co-expressed GFAPwas signicant reduced by the effect of 24-hnoise exposureas comparedto controls.Asteriskindicates statistically signicant differences(P < 0.05; Mann–Whitney “U” test). Scale bars in A–B= 50 m; in C–D= 15 m.

by stress, which is also associated with an increase in apoptosisin these cells; (3) the survival of Type-2 cells is also affected bystress, but the apoptosis rate is opposite to that found in radialastrocytes; and (4) Mature neuron population is not affected bystress and the apoptosis rate persists slightly reduced in the stressgroup. Taken together, these ndings indicate that chronic expo-sure to environmental noise induces a persistent increase in CORTlevels and produces differential effects on proliferation/apoptosisin hippocampal progenitors.

Hippocampus is an important target for detrimental effects of environmental stressors. Stress reduces the glial proliferation inseveral hippocampal regions, such as CA1, CA3, dentate gyrus andhilus ( Tanakaet al.,1997;Wonget al.,2004;Zhe etal.,2008 ). More-over, stress promotes apoptosis of pyramidal neurons in CA1 andCA3 (Li et al., 2010; Zhao et al., 2007 ). Deleterious effects of stresshave been related to an increased activity of the hypothalamic-pituitary axis (HPA) system, which increases the serum levels of glucocorticoids ( Li et al., 2010; Yehuda, 2009 ). High glucocorti-coid levelssuppress neurogenesis and induce dendritic remodelingin CA3 pyramidal neurons ( Gould et al., 1992 ). Additionally, glu-cocorticoids promote glutamate releasing in CA1 hippocampusand prefrontal cortex ( Moghaddam et al., 1994; Stein-Behrenset al., 1994; Venero and Borrell, 1999 ). Non-transcriptional effectsmediated by the mineralocorticoid receptor in hippocampus ( deKloet et al., 2008; Karst et al., 2005; Olijslagers et al., 2008 ), G

protein-coupled receptors ( Tasker et al., 2006 ) and high activityof acetylcholinesterase enzyme have also been involved in stress-induced brain disorders ( Sembulingam et al., 2003 ).

Noise is a well-known model to induce stress ( Gesi et al., 2001;Kim et al., 2008; Rabat et al., 2004 ). In this study, we used a val-idated model in which a rodents’ audiogram-tted adaptation of noisy human environments ( Rabat et al., 2005 ). This model signif-icantly increases the levels of CORT ( Jauregui-Huerta et al., 2010;Rabatet al., 2004;Rabat et al., 2005 ). The noise-induced elevation of CORT found in our study was similar to that reported in other stud-ies, which has proven to activate the glucocorticoid receptors andmodify the hypothalamus-pituitary axis ( Manikandan et al., 2006;Masini et al., 2008 ). Although, both 12-h and 24-h noise exposureactivates the HPA, our ndings indicate that a sustained exposureto 24-h noise for 10 days is a potent stressor. This incessant noisedid not allow adaptation as shown by continuous high CORT levels.Thus, we preferred the 24-h noise exposure used in this study overthe intermittent noise model described in other studies ( Jauregui-Huerta et al., 2010; Rabat et al., 2004; Rabat et al., 2005 ). Noiseexposure has been used as a model of sleep deprivation. How-ever, noise by itself is ineffective at reducing cell production in theabsence of elevated CORT levels ( Mirescu et al., 2006 ). Rather, highCORT levels appear to be necessary for the inhibition of SGZ neuro-genesis ( Mirescu et al., 2006 ). Instead, theeffects of stressand sleepdeprivation on cognitive performance and brain plasticity appearto be mediated by a reduction in BDNF expression ( Hansson et al.,2003; Taishi et al., 2001 ) and FGF-2 mRNA levels ( Molteni et al.,2001 ), anda decrease the expressionof matrix metalloproteinase-9

(Taishi et al., 2001 ).The persistent activation of glucocorticoid receptors mediated

by stress can suppress hippocampal cell proliferation ( de Kloet





Fig.4. Noiseeffects on Type-2cells. Immunostaining fordoublecortin-expressing neuroblastsand BrdU(A–B)and doublecortin/CASP-3 (C–D) in controlsand thestressgroup.The percentage of BrdU+ cells that co-expressed doublecortin was reduced by effect of noise as compared to controls. Asterisk indicate statistically signicant differences(P < 0.05; Mann–Whitney “U” test). Scale bars in A–B= 30 m; in C–D= 10 m.

et al., 2008; Wong and Herbert, 2005 ) and promote apoptosis byup-regulating the pro-apoptotic gene bax ( Cardenas et al., 2002 )and suppressing Bcl-2 expression ( DeVries et al., 2001 ). Thus,stress can affect the cell proliferation of hippocampal cells, butthe cell phenotype more susceptible to these deleterious effectswas not well-known. Our ndings indicate that stress by noiseaffects the cell proliferation of specic neuronal precursors. Type-1 radial astrocytes were the most susceptible SGZ precursors tostress, as shown by reduced proliferation and high apoptosis lev-els. Effects of stress on neuronal precursors in the SGZ have beendescribed in other studies, but this type of correlation with apo-ptosis had not been previously studied. In fact, the entire numberof newly generated neurons in the SGZ represents a combinationof the proliferative rate, the differentiation rate, and net cell sur-vival/apoptosis ( Aberg et al., 2000; D’Ercole et al., 2002 ). SinceType-1 cells that incorporate BrdU may be also suffering earlyapoptosis, our ndings suggest that the reduction in the num-ber of GFAP+ BrdU+ cells could be, in fact, a consequence of theincrease in apoptosisrate in these proliferating cells (i.e.,the higherapoptosis the lesser read-out of proliferation). Remarkably, thisopposite ratio apoptosis/proliferation was reversed at a later stageof cell maturation as shown by the analysis of Type-2 cells. Wefound that the number of BrdU+ Type-2 cells in the stress groupwas lesser than in the controls, but, a low apoptosis rate was alsoobserved in the stress group when compared to controls. Inter-estingly, the number of BrdU+ granular neurons did not show

signicant differences, whereas the apoptosis rate in the stressgroup remained slightly reduced. In fact, the given NeuN data sug-gest a promoting effect of noise on neuronal differentiation or a

compensatory mechanism to protect granular neurons from death,see below.

Opposite effects on different cell lineage may represent adap-tive actions of glucocorticoids as shown in adrenalectomy models(Nichols et al., 2005 ), where up-regulation of bax gene promotesapoptosis and the bcl-2 induction provides a compensatory mech-anism to protect the cells from death in the SGZ ( Cardenas et al.,2002 ). Such compensatory interactions between cell proliferationand apoptosis have also been found in other multipotent cells andexperimental models ( Cheraet al., 2009;Fan andBergmann, 2008b;Hawkins et al., 2000; Wells et al., 2006 ). This compensatory mech-anism may involve CASP-3 initiators (Dronc, DrICE or Dcp-1) viathe p53, Jun N-terminal kinase, Wnt-3 and Hedgehog signaling(Bergantinos et al., 2010; Fan and Bergmann, 2008a ). Neverthe-less, the knowledge is still limited about the role of apoptosis inregulating adult neurogenesis in the SGZ, but it has been suggestedthat up-regulation of transforming growth factor- 1 (Bye et al.,2001 ) and insulin-like growth factor-1 ( Aberg et al., 2000; D’Ercoleet al., 2002 ) may protect against apoptosis. Therefore, it is possiblethatglucocorticoids trigger compensatorymechanisms,which maymitigate detrimental effects of stress on SGZ progenitors ( Fig. 6).Nevertheless, further studies that include adrenalectomized ani-mals and exogenous corticosterone would be needed to fullyaddress this process.

In summary, the total number of newly generated neurons inthe SGZis a combination of theproliferative rate,the differentiation

rate, and the net cell survival/apoptosis. Present ndings indicatethat stress by environmental noise reduces the proliferation rateof radial astrocytes and Type D cells. However, these changes do





Fig. 5. Noise effects on mature granular neurons. Fluorescent double-immunostaining for NeuN and BrdU in controls and the stress group (A–B) and NeuN/CASP-3 (C–D) in

controls and the stress group. No statistically signicant differences were found in the percentage of BrdU+/NeuN+ cells between groups. P = 0.34; Mann–Whitney “ U” test).Scale bars in A–B= 50 m; in C–D= 15 m.

Fig. 6. Hypothetical modelof a possiblecompensatoryeffect to preservethe cell population in the SGZ.Stress promotesapoptosis ratein Type-1 astrocytes but not in Type-2neuroblasts. Interestingly, the net number of neurons is not affected by changes in proliferation and apoptosis.





not appear to affect the net number of granular neurons, whichsuggests a compensatory interaction between cell proliferationandapoptosis. Yet, further studies are necessary to clarify the cellularand molecular mechanisms involved in this possible interaction.

Acknowledgements

This work was supported by CONACyT’s (Ciencia Basica-2008-101476).

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Stress by Noise Produces Differential Effects on the Proliferation Rate of Radial Astrocytes

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