Klein, R. S. & Hunter, C. A. Protective and pathological Immunity during central nervous system infections. Immunity 46, 891–909 (2017).
McManus, R. M. & Heneka, M. T. Role of neuroinflammation in neurodegeneration: new insights. Alzheimers Res. Ther. 9, 14 (2017).
Bigna, J. J. et al. Global, regional, and country seroprevalence of Toxoplasma gondii in pregnant women: a systematic review, modelling and meta-analysis. Sci. Rep. 10, 12102 (2020).
Sutterland, A. L. et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatr. Scand. 132, 161–179 (2015).
Burgdorf, K. S. et al. Large-scale study of Toxoplasma and cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain Behav. Immun. 79, 152–158 (2019).
Vyas, A., Kim, S. K., Giacomini, N., Boothroyd, J. C. & Sapolsky, R. M. Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc. Natl Acad. Sci. USA 104, 6442–6447 (2007).
Martynowicz, J., Augusto, L., Wek, R. C., Boehm II, S. L. & Sullivan Jr, W. J. Guanabenz reverses a key behavioral change caused by latent toxoplasmosis in mice by reducing neuroinflammation. mBio 10, e00381-19 (2019).
Laing, C., Blanchard, N. & McConkey, G. A. Noradrenergic signaling and neuroinflammation crosstalk regulate Toxoplasma gondii-induced behavioral changes. Trends Immunol. 41, 1072–1082 (2020).
Zipp, F., Bittner, S. & Schafer, D. P. Cytokines as emerging regulators of central nervous system synapses. Immunity 56, 914–925 (2023).
Yang, L., Huh, J. R. & Choi, G. B. One messenger shared by two systems: how cytokines directly modulate neurons. Curr. Opin. Neurobiol. 80, 102708 (2023).
Felger, J. C. & Lotrich, F. E. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246, 199–229 (2013).
Song, C., Zhang, Y. & Dong, Y. Acute and subacute IL-1beta administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration. J. Neuroinflam. 10, 59 (2013).
Liu, X. et al. Cell-type-specific interleukin 1 receptor 1 signaling in the brain regulates distinct neuroimmune activities. Immunity 50, 317–333.e6 (2019).
Madabhushi, R. et al. Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 161, 1592–1605 (2015).
Suberbielle, E. et al. DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice. Nat. Commun. 6, 8897 (2015).
Suberbielle, E. et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-beta. Nat. Neurosci. 16, 613–621 (2013).
Machour, F. E. & Ayoub, N. Transcriptional regulation at DSBs: mechanisms and consequences. Trends Genet. 36, 981–997 (2020).
Habbas, S. et al. Neuroinflammatory TNFalpha impairs memory via astrocyte signaling. Cell 163, 1730–1741 (2015).
Salvioni, A. et al. Robust control of a brain-persisting parasite through MHC I presentation by infected neurons. Cell Rep. 27, 3254–3268.e8 (2019).
Porte, R. et al. Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent Toxoplasma gondii infection. Proc. Natl Acad. Sci. USA 121, e2403054121 (2024).
DiSabato, D. J. et al. Interleukin-1 receptor on hippocampal neurons drives social withdrawal and cognitive deficits after chronic social stress. Mol. Psychiatry 26, 4770–4782 (2021).
Palin, K. et al. Interleukin-1beta mediates the memory impairment associated with a delayed type hypersensitivity response to bacillus Calmette–Guérin in the rat hippocampus. Brain Behav. Immun. 18, 223–230 (2004).
Reverchon, F. et al. Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments. J. Neuroinflam. 17, 268 (2020).
Erdmann, G., Schutz, G. & Berger, S. Inducible gene inactivation in neurons of the adult mouse forebrain. BMC Neurosci. 8, 63 (2007).
Goshen, I. et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol. Psychiatry 13, 717–728 (2008).
Vanderheiden, A. et al. Vaccination reduces central nervous system IL-1beta and memory deficits after COVID-19 in mice. Nat. Immunol. 25, 1158–1171 (2024).
Marty, F. H. et al. Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity. iScience 25, 103621 (2022).
Stott, R. T., Kritsky, O. & Tsai, L. H. Profiling DNA break sites and transcriptional changes in response to contextual fear learning. PLoS ONE 16, e0249691 (2021).
Pollina, E. A. et al. A NPAS4-NuA4 complex couples synaptic activity to DNA repair. Nature 614, 732–741 (2023).
Celeste, A. et al. Genomic instability in mice lacking histone H2AX. Science 296, 922–927 (2002).
Fernandez-Albert, J. et al. Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus. Nat. Neurosci. 22, 1718–1730 (2019).
Schubert, M. et al. Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat. Commun. 9, 20 (2018).
Garza-Lombo, C. & Gonsebatt, M. E. Mammalian target of rapamycin: its role in early neural development and in adult and aged brain function. Front. Cell Neurosci. 10, 157 (2016).
Losing, P. et al. SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model. Mol. Brain 10, 30 (2017).
Roseti, C. et al. GABAA currents are decreased by IL-1beta in epileptogenic tissue of patients with temporal lobe epilepsy: implications for ictogenesis. Neurobiol. Dis. 82, 311–320 (2015).
Vezzani, A. & Viviani, B. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology 96, 70–82 (2015).
Hardingham, G. E. & Bading, H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat. Rev. Neurosci. 11, 682–696 (2010).
Choi, B. et al. Neuroprotective effects of linear ubiquitin E3 ligase against aging-induced DNA damage and amyloid beta neurotoxicity in the brain of Drosophila melanogaster. Biochem. Biophys. Res. Commun. 637, 196–202 (2022).
Madabhushi, R., Pan, L. & Tsai, L. DNA damage and its links to neurodegeneration. Neuron 83, 266–282 (2014).
Delint-Ramirez, I. et al. Calcineurin dephosphorylates topoisomerase IIbeta and regulates the formation of neuronal-activity-induced DNA breaks. Mol. Cell 82, 3794–3809 (2022).
Welch, G. M. et al. Neurons burdened by DNA double-strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration. Sci. Adv. 8, eabo4662 (2022).
Tyebji, S., Seizova, S., Garnham, A. L., Hannan, A. J. & Tonkin, C. J. Impaired social behaviour and molecular mediators of associated neural circuits during chronic Toxoplasma gondii infection in female mice. Brain Behav. Immun. 80, 88–108 (2019).
Glausen, T. G. et al. The Toxoplasma polymorphic effector GRA15 mediates seizure induction by modulating interleukin-1 signaling in the brain. mBio 12, e0133121 (2021).
Batista, S. J. et al. Gasdermin-d-dependent IL-1alpha release from microglia promotes protective immunity during chronic Toxoplasma gondii infection. Nat. Commun. 11, 3687 (2020).
Skelly, D. T. et al. Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms. Mol. Psychiatry 24, 1533–1548 (2019).
Reale, M., Costantini, E. & Greig, N. H. Cytokine imbalance in schizophrenia. From research to clinic: potential implications for treatment. Front. Psychiatry 12, 536257 (2021).
Soderlund, J. et al. Elevation of cerebrospinal fluid interleukin-1ss in bipolar disorder. J. Psychiatry Neurosci. 36, 114–118 (2011).
Soderlund, J. et al. Activation of brain interleukin-1beta in schizophrenia. Mol. Psychiatry 14, 1069–1071 (2009).
Ng, A. et al. IL-1beta, IL-6, TNF- alpha and CRP in elderly patients with depression or Alzheimer’s disease: systematic review and meta-analysis. Sci. Rep. 8, 12050 (2018).
Boza-Serrano, A., Yang, Y., Paulus, A. & Deierborg, T. Innate immune alterations are elicited in microglial cells before plaque deposition in the Alzheimer’s disease mouse model 5xFAD. Sci. Rep. 8, 1550 (2018).
Schaeffer, M. et al. Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii. J. Immunol. 182, 6379–6393 (2009).
Paredes-Santos, T., Wang, Y., Waldman, B., Lourido, S. & Saeij, J. P. The GRA17 parasitophorous vacuole membrane permeability pore contributes to bradyzoite viability. Front. Cell Infect. Microbiol. 9, 321 (2019).
Betourne, A. et al. Hippocampal expression of a virus-derived protein impairs memory in mice. Proc. Natl Acad. Sci. USA 115, 1611–1616 (2018).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).