PerspectivesDecoupling between reduced sleep spindles and impaired PPI in the VMCalb1-ablated miceIn patients with schizophrenia, reduced sleep spindles and impaired PPI can be observed 5,6), which have been proposed as biomarkers of schizophrenia 4,7). This study assesses sleep spindles and PPI in the same mice, allowing us to check the relationship between sleep spindles and PPI. As we can see in the VMCalb1-ablated mice, sleep spindles are reduced in the frontal EEG (Fig. 3C). However, PPI is not impaired, compared to the control mice (Fig. 4A), indicating the VM is crucial to the generation of sleep spindles but may not necessarily contribute to sensorimotor gating. The results point out the decoupling between reduced sleep spindles and impaired PPI. Clinical evidence has shown that impaired sleep spindles are present in the first-degree relatives of patients with schizophrenia 2). However, a meta-analysis has pointed out that PPI is intact in the first-degree relatives of patients with schizophrenia 8). Therefore, the reduction of sleep spindles may come before the diagnosis of schizophrenia. Impaired PPI may emerge and be observed during the first-episode psychosis that is triggered by a second hit, leading to the full development of schizophrenia 9,10). In the future study, it is interesting to challenge the VMCalb1-ablated mice with a second hit, such as stress or infection, to see whether impaired PPI or psychosis-like behaviors can be observed.AcknowledgmentsWe are deeply grateful to the Chugai Foundation for Innovative Drug Discovery Science (C-FINDs) for providing funding for this research.References1. Virag, D, Homolak, J, Kodvanj, I, Babic Perhoc, A, Knezovic, A, Osmanovic Barilar, J: Repurposing a digital kitchen scale for neuroscience research: a complete hardware and software cookbook for PASTA. Sci Rep, 11, 2963 (2021).2. Manoach, DS, Demanuele, C, Wamsley, EJ, Vangel, M, Montrose, DM, Miewald, J, Kupfer, D, Buysse, D, Stickgold, R, Keshavan, MS: Sleep spindle deficits in antipsychotic-naïve early course schizophrenia and in non-psychotic first-degree relatives. Front. Hum. Neurosci., 8, (2014).3. Meyer, U and Feldon: J. Neural basis of psychosis-related behaviour in the infection model of schizophrenia. Behavioural Brain Research, 204, 322–334 (2009).4. Mena, A, Ruiz-Salas, JC, Puentes, A, Dorado, I, Ruiz-Veguilla, M, De la Casa, LG: Reduced Prepulse Inhibition as a Biomarker of Schizophrenia. Front. Behav. Neurosci., 10, (2016).5. Braff, D, Stone, C, Callaway, E, Geyer, M, Glick, I, Bali, L: Prestimulus Effects on Human Startle Reflex in Normals and Schizophrenics. Psychophysiology, 15, 339–343 (1978).6. Ferrarelli, F. et al. Reduced Sleep Spindle Activity in Schizophrenia Patients. AJP, 164, 483–492 (2007).7. Ferrarelli, F: Sleep spindles as neurophysiological biomarkers of schizophrenia. Eur J Neurosci, 59, 1907–1917 (2024).8. Li, W, Mao, Z, Bo, Q, Sun, Y, Wang, Z, Wang, C: Prepulse inhibition in first-degree relatives of schizophrenia patients: A systematic review. Early Intervention Psych, 15, 652–661 (2021).9. Millan, MJ, Andrieux, A, Bartzokis, G, Cadenhead, K, Dazzan, P, Fusar-Poli, P, Gallinat, J, Giedd, J, Grayson, DR, Heinrichs, M, Kahn, R, Krebs, M-O, Leboyer, M, Lewis, D, Marin, O, Marin, P, Meyer-Lindenberg, A, McGorry, P, McGuire, P, Owen, MJ, Patterson, P, Sawa, A, Spedding, M, Uhlhaas, P, ― 260 ―
元のページ ../index.html#262