title: Electrical brain stimulation induces dendritic stripping but improves survival of silent neurons after optic nerve damage.
abstract: Repetitive transorbital alternating current stimulation (rtACS) improves vision in patients with chronic visual impairments and an acute treatment increased survival of retinal neurons after optic nerve crush (ONC) in rodent models of visual system injury. However, despite this protection no functional recovery could be detected in rats, which was interpreted as evidence of "silent survivor" cells. We now analysed the mechanisms underlying this "silent survival" effect. Using in vivo microscopy of the retina we investigated the survival and morphology of fluorescent neurons before and after ONC in animals receiving rtACS or sham treatment. One week after the crush, more neurons survived in the rtACS-treated group compared to sham-treated controls. In vivo imaging further revealed that in the initial post-ONC period, rtACS induced dendritic pruning in surviving neurons. In contrast, dendrites in untreated retinae degenerated slowly after the axonal trauma and neurons died. The complete loss of visual evoked potentials supports the hypothesis that cell signalling is abolished in the surviving neurons. Despite this evidence of "silencing", intracellular free calcium imaging showed that the cells were still viable. We propose that early after trauma, complete dendritic stripping following rtACS protects neurons from excitotoxic cell death by silencing them.
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany. petra.henrich-noack@med.ovgu.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Henrich-Noack
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.|Department of Emergency Medicine, Emory University, Atlanta, USA.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Sergeeva
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.|Institute of Statistics, Magdeburg-Stendal University of Applied Sciences, Magdeburg, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Eber
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Qing
authors.initials: Q
authors.lastname: You
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Voigt
authors.affiliation: Institute of Statistics, Magdeburg-Stendal University of Applied Sciences, Magdeburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Köhler
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lazik
authors.affiliation: Institute of Neuropathology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, P.R. China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, P.R. China.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Institute of Medical Psychology, Center for Behavioral Brain Sciences, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Sabel
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, P.R. China. cksleung@gmail.com.
authors.forename: Christopher Kai-Shun
authors.initials: CK
authors.lastname: Leung
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D003712:Dendrites / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy; D005074:Evoked Potentials, Visual; D051379:Mice; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D020221:Optic Nerve Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051381:Rats; D012160:Retina / Q000166:cytology / Q000378:metabolism