Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice

Fuss, Johannes; Ben Abdallah, Nada M. B.; Hensley, Frank W.; Weber, Klaus-Josef; Hellweg, Rainer; Gass, Peter

doi:10.1371/journal.pone.0012769

Cited by 110Neurogenesis and neuroplasticity mechanismsMemory and Neural MechanismsStress Responses and Cortisol

Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice

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Fuss, Johannes, Ben Abdallah, Nada M. B., Hensley, Frank W., Weber, Klaus-Josef, Hellweg, Rainer, Gass, Peter·2010·PLoS ONE

DOI 10.1371/journal.pone.0012769PMC PMC2940841

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Abstract

Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF) by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety.

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Previous studies have shown an increased anxiety-like phenotype in consequence of increased neurogenesis induced by voluntary wheel running.
“Moreover, previous studies have shown an increased anxiety-like phenotype in consequence of increased neurogenesis induced by voluntary wheel running.37, 38, 39”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [38]

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“[8,11,12,13,17,18,19,20,22,23,24,25,26,32,36,37,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62] Using a random effects model and Hedge’s estimator, analysis of contextual freezing was significant at a 5% level (P = 0.”
BackgroundMethod
Exercise offers anxiolytic potential: A role for stress and brain noradrenergic-galaninergic mechanisms
Sciolino, N. R., & Holmes, P. V. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.06.005 · Cited by 116 · see citing works
The effects of physical exercise in schizophrenia and affective disorders.
Malchow, B., Reich-Erkelenz, D., Oertel-Knöchel, V., Keller, K., Hasan, A., Schmitt, A., Scheewe, T. W., Cahn, W., Kahn, R. S., & Falkai, P. (2013) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-013-0423-2 · Cited by 111 · see citing works
“Physical exercise may exert antidepressant effects via the peptide precursor of neurotrophic factors VGF [73] or serotonergic 5-HT1A receptors [51] and via neurogenesis [41].”
In vivo voxel based morphometry: Detection of increased hippocampal volume and decreased glutamate levels in exercising mice
Biedermann, S. V., Fuß, J., Zheng, L., Sartorius, A., Falfán-Melgoza, C., Demirakça, T., Gass, P., Ende, G., & Weber‐Fahr, W. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.04.010 · Cited by 111 · see citing works
“Our earlier observations, where we found the number of dying cells being dramatically reduced in running mice, support the latter (Fuss et al., 2010b).”
InfluentialSelf-citation
Mechanisms of antidepressant resistance
El-Hage, W., Leman, S., Camus, V., & Belzung, C. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00146 · Cited by 111 · see citing works
“Finally, hippocampal neurogenesis have also been proposed to be crucial for anxiety behavior (Revest et al., 2009; Fuss et al., 2010; Mateus-Pinheiro et al., 2013) or executive functions (Burghardt et al., 2012); if restored, these functions would enable the subject to react more accurately to the…”
Background
Inflammation and the developing brain: Consequences for hippocampal neurogenesis and behavior
Green, H. F., & Nolan, Y. M. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.01.004 · Cited by 111 · see citing works
Functional Role of Adult Hippocampal Neurogenesis as a Therapeutic Strategy for Mental Disorders
Jun, H., Hussaini, S. M. Q., Rigby, M. J., & Jang, M. (2012) · Neural Plasticity · doi:10.1155/2012/854285 · Cited by 108 · see citing works
The Clinical Implications of Mouse Models of Enhanced Anxiety
Sartori, S. B., Landgraf, R., & Singewald, N. (2011) · Future Neurology · doi:10.2217/fnl.11.34 · Cited by 97 · see citing works
“On the other hand, C57Bl/6J mice pre-selected for voluntary wheelrunning also exhibit an anxiogenic phenotype in the open-field, light/dark and elevated Omaze tests compared with sedentary animals [97].”
The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age
Saraulli, D., Costanzi, M., Mastrorilli, V., & Vecchioli, S. F. (2017) · Current Neuropharmacology · doi:10.2174/1570159x14666160412150223 · Cited by 96 · see citing works
“Intriguingly, decreasing neurogenesis by focalized irradiation of the hippocampus abolished the running-dependent enhancement of anxiety [145].”
Mood disorders in Huntington's disease: from behavior to cellular and molecular mechanisms
Pla, P., Orvoën, S., Saudou, F., David, D. J. P., & Humbert, S. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00135 · Cited by 91 · see citing works
Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety- and depressive-like behaviors in rats
Otsuka, T., Nishii, A., Amemiya, S., Kubota, N., Nishijima, T., & Kita, I. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.10.055 · Cited by 86 · see citing works
“[64,65] may be partially due to difference of type of the exercise or the behavioral test.”
The protective effects of voluntary exercise against the behavioral consequences of uncontrollable stress persist despite an increase in anxiety following forced cessation of exercise
Greenwood, B. N., Loughridge, A. B., Sadaoui, N. C., Christianson, J. P., & Fleshner, M. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.05.017 · Cited by 82 · see citing works
Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression
Alves, N. D., Correia, J. S., Patrício, P., Mateus-Pinheiro, A., Machado-Santos, A. R., Loureiro-Campos, E., Morais, M., Bessa, J. M., Sousa, N., & Pinto, L. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.29 · Cited by 79 · see citing works
Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety
Pan-Vazquez, A., Rye, N., Ameri, M., McSparron, B., Smallwood, G., Bickerdyke, J., Rathbone, A., Dajas‐Bailador, F., & Toledo‐Rodriguez, M. (2015) · Molecular Brain · doi:10.1186/s13041-015-0128-8 · Cited by 80 · see citing works
“Interestingly the decrease in open arm entry/time by exercise was mechanistically related to hippocampal neurogenesis [50, 34, 51].”
Background
Electroconvulsive Therapy Induces Neurogenesis in Frontal Rat Brain Areas
Inta, D., Lima‐Ojeda, J. M., Lau, T., Tang, W., Dormann, C., Sprengel, R., Schloss, P. D., Sartorius, A., Meyer‐Lindenberg, A., & Gass, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069869 · Cited by 78 · see citing works
“For this purpose, 50 mm coronal free floating vibratome sections were processed as described previously [18] and washed in 0.”
MethodSelf-citation
Cessation of voluntary wheel running increases anxiety-like behavior and impairs adult hippocampal neurogenesis in mice
Nishijima, T., Llorens-Martı́n, M., Tejeda, G. S., Inoue, K., Yamamura, Y., Soya, H., Trejo, J. L., & Torres‐Alemán, I. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.02.009 · Cited by 77 · see citing works
The hippocampus and exercise: histological correlates of MR-detected volume changes
Biedermann, S. V., Fuss, J., Steinle, J., Auer, M. K., Dormann, C., Falfán-Melgoza, C., Ende, G., Gass, P., & Weber-Fahr, W. (2016) · Brain Structure and Function · doi:10.1007/s00429-014-0976-5 · Cited by 72 · see citing works
“Runners were given free access to a running wheel, and controls were supplied with a blocked wheel for 8–10 weeks as described before (Fuss et al. 2010).”
Self-citation
Depression‐related behaviours displayed by female C 57 BL /6 J mice during abstinence from chronic ethanol consumption are rescued by wheel‐running
Pang, T. Y., Renoir, T., Du, X., Lawrence, A. J., & Hannan, A. J. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12195 · Cited by 73 · see citing works
“However, recent evidence provided by others (Arunrut et al., 2009; Fuss et al., 2010b) and our group (Renoir et al., 2012) suggests otherwise.”
Result
Gene-environment interactions informing therapeutic approaches to cognitive and affective disorders
Rogers, J., Renoir, T., & Hannan, A. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.12.038 · Cited by 69 · see citing works
Hippocampal neurogenesis: a biomarker for depression or antidepressant effects? Methodological considerations and perspectives for future research
Tanti, A., & Belzung, C. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1612-z · Cited by 71 · see citing works
Regular treadmill running improves spatial learning and memory performance in young mice through increased hippocampal neurogenesis and decreased stress
Li, H., Liang, A., Guan, F., Fan, R., Chi, L., & Yang, B. (2013) · Brain Research · doi:10.1016/j.brainres.2013.07.041 · Cited by 67 · see citing works
Resting Is Rusting
Richter, S. H., Gass, P., & Fuß, J. (2014) · The Neuroscientist · doi:10.1177/1073858413516798 · Cited by 63 · see citing works
Self-citation
Voluntary wheel running in mice increases the rate of neurogenesis without affecting anxiety-related behaviour in single tests
Garrett, L., Lie, D. C., de Angelis, M. H., Wurst, W., & Hölter, S. M. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-61 · Cited by 62 · see citing works
“[36].”
Voluntary exercise offers anxiolytic potential and amplifies galanin gene expression in the locus coeruleus of the rat
Sciolino, N. R., Dishman, R. K., & Holmes, P. V. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.05.001 · Cited by 60 · see citing works
The Effects of Exercise Training on Anxiety
Herring, M. P., Lindheimer, J. B., & O’Connor, P. J. (2013) · American Journal of Lifestyle Medicine · doi:10.1177/1559827613508542 · Cited by 61 · see citing works
S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms
Mendez‐David, I., Guilloux, J., Papp, M., Tritschler, L., Mocaër, E., Gardier, A. M., Bretin, S., & David, D. J. P. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00462 · Cited by 59 · see citing works
“These results are in line with prior observation that irradiation did not affect exercise-induced increase in BDNF levels in the hippocampus (Fuss et al., 2010).”
Result
Galanin mediates features of neural and behavioral stress resilience afforded by exercise
Sciolino, N. R., Smith, J. M., Stranahan, A. M., Freeman, K. G., Edwards, G. L., Weinshenker, D., & Holmes, P. V. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.09.029 · Cited by 59 · see citing works
“These phenomena may contribute to the affective consequences of exercise, though the evidence for their specific roles is mixed (Duman et al., 2008; Duman et al., 2009; Fuss et al., 2010; Greenwood et al., 2007b; Li et al., 2008; Llorens-Martin et al., 2010; Trejo et al., 2008).”
Background
DISC1 in Astrocytes Influences Adult Neurogenesis and Hippocampus-Dependent Behaviors in Mice
Terrillion, C. E., Abazyan, B. N., Yang, Z., Crawford, J. A., Shevelkin, A. V., Jouroukhin, Y., Yoo, K. H., Cho, C. H., Roychaudhuri, R., Snyder, S. H., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.129 · Cited by 58 · see citing works
“However, there are also a number of negative reports on the effects of adult neurogenesis on affective behaviors and/or responses to antidepressants (Fuss et al, 2010; Jun et al, 2012a; Wang et al, 2008).”
Background
Novel Insights into Depression and Antidepressants: A Synergy Between Synaptogenesis and Neurogenesis?
Bambico, F. R., & Belzung, C. (2012) · Current topics in behavioral neurosciences · doi:10.1007/7854_2012_234 · Cited by 57 · see citing works
“2009) or the anxiolytic effects of running in the open field and in the light/dark tests (Fuss et al. 2010).”
Background
Lack of cyclin D2 impairing adult brain neurogenesis alters hippocampal-dependent behavioral tasks without reducing learning ability
Jedynak, P., Jaholkowski, P. P., Woźniak, G., Sandi, C., Kaczmarek, L., & Filipkowski, R. K. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.11.007 · Cited by 55 · see citing works
“On the other hand, physical activity increases neurogenesis [40,41], moreover, several recent findings suggest that running-induced neurogenesis increases anxiety in mice and rats [42].”
Background
Voluntary wheel running ameliorates depression-like behaviors and brain blood oxygen level-dependent signals in chronic unpredictable mild stress mice
Huang, P., Dong, Z., Huang, W., Zhou, C., Zhong, W., Hu, P., Wen, G., Sun, X., Hua, H., Cao, H., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.05.032 · Cited by 54 · see citing works
“Indeed, there is conflicting evidence that running has also been reported to increase anxiety-related behavior in mice [3,4], because of the form and intensity of the exercise [5], the duration of the intervention [6], and housing conditions [7].”
Background
Unlocking mechanisms in interleukin-1β-induced changes in hippocampal neurogenesis—a role for GSK-3β and TLX
Green, H. F., & Nolan, Y. M. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.117 · Cited by 51 · see citing works
Stress-Induced Anxiety- and Depressive-Like Phenotype Associated with Transient Reduction in Neurogenesis in Adult Nestin-CreERT2/Diphtheria Toxin Fragment A Transgenic Mice
Yun, S., Donovan, M. H., Ross, M. N., Richardson, D. R., Reister, R., Farnbauch, L. A., Fischer, S. J., Riethmacher, D., Gershenfeld, H. K., Lagace, D. C., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147256 · Cited by 50 · see citing works
“However, there is not a straightforward relationship between new neuron number and anxiety, since both running-induced enhancement in adult neurogenesis and ablation of the running-induced enhancement are anxiogenic [86, 87].”
Background
Impaired long-term memory retention: Common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice
Abdallah, N. M. ‐. B., Filipkowski, R. K., Pruschy, M. N., Jaholkowski, P. P., Winkler, J., Kaczmarek, L., & Lipp, H. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.05.034 · Cited by 43 · see citing works
Modulation of Adult Hippocampal Neurogenesis by Sleep: Impact on Mental Health
Navarro-Sanchis, C., Brock, O., Winsky‐Sommerer, R., & Thuret, S. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00074 · Cited by 41 · see citing works
“Indeed, suppression of neurogenesis alone in rats did not lead to depressive or anxious phenotypes (Santarelli et al., 2003; Wang et al., 2008; Jayatissa et al., 2009; Fuss et al., 2010) while mice did show neither enhanced depressive-like behaviors (Eisch and Petrik, 2012).”
Background
Early effects of a high-caloric diet and physical exercise on brain volumetry and behavior: a combined MRI and histology study in mice
Sack, M., Lenz, J. N., Jakovcevski, M., Biedermann, S. V., Falfán-Melgoza, C., Deussing, J. M., Bielohuby, M., Bidlingmaier, M., Pfister, F., Stalla, G. K., et al. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-016-9638-y · Cited by 39 · see citing works
“…been studied more intensively in humans (Colcombe et al. 2006; Erickson et al. 2010; Erickson et al. 2011) than in rodent models (Biedermann et al. 2016; Fuss et al. 2010b; Fuss et al. 2014) but studies investigating in parallel MRI volumetrics and underlying histological correlates are sparse.”
BackgroundMethodInfluentialSelf-citation
Association of growth hormone deficiency (GHD) with anxiety and depression: experimental data and evidence from GHD children and adolescents
Karachaliou, F.-E., Karavanaki, K., Simatou, A., Tsintzou, E., Skarakis, N., & Kanaka‐Gantenbein, C. (2021) · HORMONES · doi:10.1007/s42000-021-00306-1 · Cited by 39 · see citing works
Voluntary exercise counteracts Aβ25-35-induced memory impairment in mice
Wang, Q. L., Xu, Z., Tang, J., Sun, J., Gao, J., Wu, T., & Xiao, M. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.09.024 · Cited by 37 · see citing works
Pomegranate Supplementation Improves Affective and Motor Behavior in Mice after Radiation Exposure
Dulcich, M. S., & Hartman, R. E. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/940830 · Cited by 36 · see citing works
“One study reported that exercise-induced elevated levels of hippocampal neurogenesis were correlated with increased anxiety-like behavior on the O-maze (analogous to the zero maze), the open field, and dark/light box, but that radiation attenuated this effect, leading to reduced anxietylike behaviors in mice, thus sug…”
Background
Phenotype of mice with inducible ablation of GluA1 AMPA receptors during late adolescence: Relevance for mental disorders
Inta, D., Vogt, M. A., Elkin, H., Weber, T., Lima‐Ojeda, J. M., Schneider, M., Luoni, A., Riva, M. A., Gertz, K. R., Hellmann‐Regen, J., et al. (2013) · Hippocampus · doi:10.1002/hipo.22236 · Cited by 33 · see citing works
“Activity monitoring was conducted in a square-shaped, white open field, measuring 50 3 50 cm(2) and illuminated by 25 lx (Fuss et al., 2010).”
MethodSelf-citation
Exercise boosts hippocampal volume by preventing early age-related gray matter loss: Exercise Modulates Hippocampal Aging
Fuss, J., Biedermann, S. V., Falfán-Melgoza, C., Auer, M. K., Zheng, L., Steinle, J., Hörner, F., Sartorius, A., Ende, G., Weber-Fahr, W., et al. (2014) · Hippocampus · doi:10.1002/hipo.22227 · Cited by 32 · see citing works
“Mice were sacrificed after the second MR, and disruption of neurogenesis by irradiation was confirmed histologically using established protocols (Fuss et al., 2010a).”
MethodSelf-citation
Maternal stress during pregnancy induces depressive-like behavior only in female offspring and correlates to their hippocampal Avp and Oxt receptor expression
Schmidt, M., Braun, K., Brandwein, C., Rossetti, A. C., Ciurana, S. G., Riva, M. A., Deuschle, M., Bock, J., Gass, P., & Gröger, N. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.06.027 · Cited by 33 · see citing works
Self-citation
Dissecting the role of adult hippocampal neurogenesis towards resilience versus susceptibility to stress-related mood disorders
Jones, K. L., Zhou, M., & Jhaveri, D. J. (2022) · npj Science of Learning · doi:10.1038/s41539-022-00133-y · Cited by 32 · see citing works
Significant increase in anxiety during aging in mGlu5 receptor knockout mice
Inta, D., Vogt, M. A., Luoni, A., Filipović, D., Lima‐Ojeda, J. M., Pfeiffer, N., Gasparini, F., Riva, M. A., & Gass, P. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.11.042 · Cited by 30 · see citing works
Self-citation
Social crowding in the night-time reduces an anxiety-like behavior and increases social interaction in adolescent mice
Ago, Y., Tanaka, T., Ota, Y., Kitamoto, M., Imoto, E., Takuma, K., & Matsuda, T. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.04.047 · Cited by 30 · see citing works
Anxiolytic Actions of Exercise in Absence of New Neurons
Schoenfeld, T. J., McCausland, H. C., Sonti, A. N., & Cameron, H. A. (2016) · Hippocampus · doi:10.1002/hipo.22649 · Cited by 29 · see citing works
“running (Fuss et al., 2010; Schoenfeld et al., 2013), consistent with the anxiogenic testing situations being mildly stressful.”
Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats
Loxton, D., & Canales, J. J. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.11.003 · Cited by 29 · see citing works
“, 2008), OF (Fuss et al., 2010; Schloesser et al., 2010) and EPM tests (Saxe et al.”
Running‐induced anxiety is dependent on increases in hippocampal neurogenesis
Onksen, J. L., Briand, L. A., Galante, R. J., Pack, A. I., & Blendy, J. A. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00788.x · Cited by 29 · see citing works
“However, the data presented herein, in addition to recent literature highlighting the prevention of running-induced anxiety by X-ray irradiation (Fuss et al. 2010a,b), strengthen the hypothesis that neurogenesis directly influences the anxiety-like behavior induced by running.”
BackgroundResultInfluential
Hippocampal serotonin-1A receptor function in a mouse model of anxiety induced by long-term voluntary wheel running
Fuß, J., Vogt, M. A., Weber, K.-J., Burke, T. F., Gass, P., & Hensler, J. G. (2013) · Synapse · doi:10.1002/syn.21666 · Cited by 28 · see citing works
“1), since our previous studies had demonstrated a specific role of the hippocampus in voluntary exercise-induced anxiety, with a plethora of cellular and neurochemical alterations occurring specifically in the hippocampus following wheel running (Biedermann et al., 2012; Fuss et al., 2010b).”
BackgroundMethodInfluentialSelf-citation
α4βδ-GABAARs in the hippocampal CA1 as a biomarker for resilience to activity-based anorexia
Aoki, C. J., Wable, G. S., Chowdhury, T. G., Sabaliauskas, N. A., Laurino, K., & Barbarich-Marsteller, N. C. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.01.011 · Cited by 26 · see citing works
“, 2012) that induce neurogenesis-dependent anxiety (Fuss et al., 2010; Onksen et al., 2012).”
A Functional Tph2 C1473G Polymorphism Causes an Anxiety Phenotype via Compensatory Changes in the Serotonergic System
Berger, S. M., Weber, T., Perreau‐Lenz, S., Vogt, M. A., Gartside, S. E., Maser‐Gluth, C., Lanfumey, L., Gass, P., Spanagel, R., & Bartsch, D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.46 · Cited by 28 · see citing works
Self-citation
Selective Deletion of a Cell Cycle Checkpoint Kinase (ATR) Reduces Neurogenesis and Alters Responses in Rodent Models of Behavioral Affect
Onksen, J. L., Brown, E. J., & Blendy, J. A. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.234 · Cited by 27 · see citing works
“Voluntary exercise leads to a robust increase in neurogenesis while also increasing anxiety-like behavior (Fuss et al., 2010).”
Influential
Adult AMPA GLUA1 Receptor Subunit Loss in 5-HT Neurons Results in a Specific Anxiety-Phenotype with Evidence for Dysregulation of 5-HT Neuronal Activity
Weber, T., Vogt, M. A., Gartside, S. E., Berger, S. M., Luján, R., Lau, T., Herrmann, E., Sprengel, R., Bartsch, D., & Gass, P. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.332 · Cited by 28 · see citing works
Self-citation
Large‐scale phenotyping links adult hippocampal neurogenesis to the reaction to novelty
van Dijk, R. M., Lazic, S. E., Slomianka, L., Wolfer, D. P., & Amrein, I. (2015) · Hippocampus · doi:10.1002/hipo.22548 · Cited by 26 · see citing works
“Sample size for each group was based on published data (Fuss et al., 2010a) in which, postpublication, a within-group analysis suggested a significant association between neurogenesis and behavior.”
BackgroundMethod
Cortical Glutamate/GABA Imbalance after Combined Radiation Exposure: Relevance to Human Deep-Space Missions
Kokhan, V. S., Anokhin, P. K., Belov, O., & Gulyaev, M. V. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.08.009 · Cited by 26 · see citing works
Physical exercise rectifies CUMS-induced aberrant regional homogeneity in mice accompanied by the adjustment of skeletal muscle PGC-1a/IDO1 signals and hippocampal function
Dong, Z., Liu, Z., Liu, Y., Zhang, R., Mo, H., Gao, L., & Shi, Y. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112516 · Cited by 25 · see citing works
Trophic Mechanisms for Exercise-Induced Stress Resilience: Potential Role of Interactions between BDNF and Galanin
Holmes, P. V. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00090 · Cited by 25 · see citing works
“With respect to neurogenesis specifically, exercise-induced hippocampal neurogenesis is associated with increased spontaneous anxiety-like behavior, an effect that is reversed after irradiation, which effectively eliminates neurogenesis (33, 34).”
Background
Are you real? Visual simulation of social housing by mirror image stimulation in single housed mice
Fuß, J., Richter, S. H., Steinle, J., Deubert, G., Hellweg, R., & Gass, P. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.01.015 · Cited by 23 · see citing works
“Five mice were excluded from the analyses after jumping off the test apparatus [28].”
Self-citation
Morc1 knockout evokes a depression-like phenotype in mice
Schmidt, M., Brandwein, C., Luoni, A., Sandrini, P., Calzoni, T., Deuschle, M., Cirulli, F., Riva, M. A., & Gass, P. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.08.005 · Cited by 21 · see citing works
Self-citation
Early-Delayed, Radiation-Induced Cognitive Deficits in Adult Rats are Heterogeneous and Age-Dependent
Forbes, M. E., Paitsel, M., Bourland, J. D., & Riddle, D. R. (2014) · Radiation Research · doi:10.1667/rr13662.1 · Cited by 21 · see citing works
“(45, 46)] consistent with evidence that patients receiving cranial radiation therapy exhibit increased levels of anxiety several years after treatment (47).”
Central monoaminergic systems are a site of convergence of signals conveying the experience of exercise to brain circuits involved in cognition and emotional behavior
Nicastro, T. M., & Greenwood, B. N. (2016) · Current Zoology · doi:10.1093/cz/zow027 · Cited by 21 · see citing works
“…and neurogenesis noted after exercise (Poo 2001; Gomez-Pinilla et al. 2008; Ding et al. 2011; Park & Poo 2013), which together could contribute to beneficial effects of exercise (Bjornebekk et al. 2005; Clark et al. 2008; Duman et al. 2008; Marais et al. 2009; Fuss et al. 2010; Voss et al. 2013).”
Background
Social isolation is associated with reduced neurogenesis, impaired spatial working memory performance, and altered anxiety levels in male rats
Karimian, M., Famitafreshi, H., Fanaei, H., Attari, F., & Fatima, S. (2015) · Open Access Animal Physiology · doi:10.2147/oaap.s84327 · Cited by 21 · see citing works
“32 The role of the amygdala in regulating neurogenesis is also quite evident.”
Effects of circulating estradiol on physiological, behavioural, and subjective correlates of anxiety: A double-blind, randomized, placebo-controlled trial
Nouri, S., Biedermann, S. V., Joue, G., Auer, M. K., Sommer, T., & Fuß, J. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105682 · Cited by 17 · see citing works
Impact of adolescent GluA1 AMPA receptor ablation in forebrain excitatory neurons on behavioural correlates of mood disorders
Vogt, M. A., Elkin, H., Pfeiffer, N., Sprengel, R., Gass, P., & Inta, D. (2014) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-014-0509-5 · Cited by 18 · see citing works
“The elevated O-Maze consisted of a grey plastic annular runway (width 6 cm, outer diameter 46 cm, 50 cm above ground level) covered with black cardboard paper to prevent mice from slipping off the maze [22, 23].”
BackgroundSelf-citation
Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits
Vogt, M. A., Inta, D., Luoni, A., Elkin, H., Pfeiffer, N., Riva, M. A., & Gass, P. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00407 · Cited by 18 · see citing works
“Mice were placed into the dark compartment and latency to first exit, number of exits and total time in the light compartment were recorded for 5 min (N = 24 per genotype) as described earlier (Fuss et al., 2010).”
MethodSelf-citation
On the quest for a biomechanism of transsexualism: Is there a role for BDNF?
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Running‐induced anxiety is dependent on increases in hippocampal neurogenesis
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Voluntary exercise induces anxiety‐like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesis
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Voluntary Exercise Induces Anxiety−Like Behavior in Adult\nC57BL/6J Mice Correlating With Hippocampal Neurogenesis
Fuss, J., Abdallah, N. M. −. B., Vogt, M. A., Touma, C., Pacifici, P. G., Palme, R., Witzemann, V., Hellweg, R., & Gass, P. (2010) · Max Planck Institute for Plasma Physics
Self-citation

Authors: Fuss, J., Ben Abdallah, N. M. B., Hensley, F. W., Weber, K.-J., Hellweg, R., & Gass, P.
Affiliations: Heidelberg University (DE)
Charité – Universitätsmedizin Berlin (DE)
Corresponding author: Fuss, Johannes
ORCID: Fuss, Johannes
Hensley, Frank W.
Hellweg, Rainer
Gass, Peter
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2010-09-16
Volume: 5
Issue: 9
Pages: e12769
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0012769
PMC: PMC2940841
OpenAlex: W2046295151
Cited by: 110
References: 50
Citations by year: 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 15 · 2013: 26 · 2012: 13
FWCI: 4.66
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Deutsche Forschungsgemeinschaft (HE 1392/3-1, SFB 636)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: hippocampal neurogenesis, anxiety, voluntary wheel running, focal irradiation, physical activity, c-fos, brain-derived neurotrophic factor, anxiety-like behavior, elevated plus maze, open field, sedentary behavior
MeSH terms: Animals, Anxiety, Hippocampus, Mice, Inbred C57BL, Phenotype, Radiotherapy, Running, X-Rays, Brain-Derived Neurotrophic Factor, Cell Proliferation, Mice, Neurogenesis

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Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice

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