Electroconvulsive Therapy Induces Neurogenesis in Frontal Rat Brain Areas

Electroconvulsive therapy (ECT) is an effective therapy for several psychiatric disorders, including severe major depression, mania and certain forms of schizophrenia. It had been proposed that ECT acts by modulating local plasticity via the stimulation of neurogenesis. In fact, among antidepressant therapies, ECT is the most robust enhancer of neurogenesis in the hippocampus of rodents and non-human primates. The existence of ECT-triggered neurogenesis in other brain areas, particularly in those adjacent to the other main locus of neurogenesis, the subventricular zone (SVZ), had so far remained unknown. Here we show that ECT also strongly enhances neurogenesis in frontal brain areas, especially in the rostro-medial striatum, generating specific, small-size calretinin-positive interneurons. We provide here the first evidence that ECT stimulates neurogenesis in areas outside the hippocampus. Our data may open research possibilities that focus on the plastic changes induced by ECT in frontal limbic circuitry.

[1]  F. Fumagalli,et al.  Repeated electroconvulsive shock (ECS) alters the phosphorylation of glutamate receptor subunits in the rat hippocampus. , 2010, The international journal of neuropsychopharmacology.

[2]  H. Monyer,et al.  Increased subventricular zone-derived cortical neurogenesis after ischemic lesion , 2010, Experimental Neurology.

[3]  H. Sackeim,et al.  Decreased regional brain metabolism after ect. , 2001, The American journal of psychiatry.

[4]  Sarah H Lisanby,et al.  Antidepressant-Induced Neurogenesis in the Hippocampus of Adult Nonhuman Primates , 2007, The Journal of Neuroscience.

[5]  R. Hellweg,et al.  Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice , 2010, PloS one.

[6]  Ronald S Duman,et al.  Electroconvulsive Seizure Treatment Increases Cell Proliferation in Rat Frontal Cortex , 2005, Neuropsychopharmacology.

[7]  R. Duman,et al.  Pathophysiology of depression: the concept of synaptic plasticity , 2002, European Psychiatry.

[8]  H. Monyer,et al.  Subventricular zone-derived neuroblasts use vasculature as a scaffold to migrate radially to the cortex in neonatal mice. , 2012, Cerebral cortex.

[9]  B. Zörner,et al.  Memory retrieval after contextual fear conditioning induces c‐Fos and JunB expression in CA1 hippocampus , 2003, Genes, brain, and behavior.

[10]  H. Cameron,et al.  New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors , 2005, The Journal of cell biology.

[11]  M. West,et al.  Electroconvulsive Seizures Induce Angiogenesis in Adult Rat Hippocampus , 2005, Biological Psychiatry.

[12]  H. Sackeim,et al.  Anticonvulsant and antidepressant properties of electroconvulsive therapy: a proposed mechanism of action. , 1983, Biological psychiatry.

[13]  A. Tingström,et al.  Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat hippocampus , 2003, Biological Psychiatry.

[14]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[15]  B. Jacobs,et al.  Adult brain neurogenesis and psychiatry: a novel theory of depression , 2000, Molecular Psychiatry.

[16]  A. Sartorius,et al.  Correlations and Discrepancies between Serum and Brain Tissue Levels of Neurotrophins after Electroconvulsive Treatment in Rats , 2009, Pharmacopsychiatry.

[17]  Konstantin Khodosevich,et al.  “Small Axonless Neurons”: Postnatally Generated Neocortical Interneurons with Delayed Functional Maturation , 2011, The Journal of Neuroscience.

[18]  K. Ressler,et al.  Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic , 2007, Nature Neuroscience.

[19]  Arturo Alvarez-Buylla,et al.  Neurogenesis in Adult Subventricular Zone , 2002, The Journal of Neuroscience.

[20]  C. Sotelo,et al.  Proliferation, migration and differentiation of neuronal progenitor cells in the adult mouse subventricular zone surgically separated from its olfactory bulb , 1998, The European journal of neuroscience.

[21]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[22]  Eric J. Nestler,et al.  Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[23]  G. Fishell,et al.  The Distinct Temporal Origins of Olfactory Bulb Interneuron Subtypes , 2008, The Journal of Neuroscience.

[24]  A. Fasolo,et al.  Neurogenesis in the Caudate Nucleus of the Adult Rabbit , 2006, The Journal of Neuroscience.

[25]  H. Monyer,et al.  Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone , 2008, Proceedings of the National Academy of Sciences.

[26]  K. Orre,et al.  Repeated Electroconvulsive Seizures Increase the Number of Vessel-Associated Macrophages in Rat Hippocampus , 2012, The journal of ECT.

[27]  Jürgen Winkler,et al.  Doublecortin expression levels in adult brain reflect neurogenesis , 2005, The European journal of neuroscience.

[28]  A. Mcgeorge,et al.  The organization of the projection from the cerebral cortex to the striatum in the rat , 1989, Neuroscience.

[29]  J. Tepper,et al.  Functional diversity and specificity of neostriatal interneurons , 2004, Current Opinion in Neurobiology.

[30]  Paul Leonard Gabbott,et al.  Calretinin neurons in human medial prefrontal cortex (areas 24a,b,c, 32′, and 25) , 1997, The Journal of comparative neurology.

[31]  Zhengang Yang,et al.  Neonatal hypoxic/ischemic brain injury induces production of calretinin‐expressing interneurons in the striatum , 2008, The Journal of comparative neurology.

[32]  Vivian V. Valentin,et al.  Prolonged Seizures Increase Proliferating Neuroblasts in the Adult Rat Subventricular Zone–Olfactory Bulb Pathway , 2002, The Journal of Neuroscience.

[33]  Zhengang Yang,et al.  Brain Injury Does Not Alter the Intrinsic Differentiation Potential of Adult Neuroblasts , 2009, The Journal of Neuroscience.

[34]  A. Johanson,et al.  Glial cell activation in response to electroconvulsive seizures , 2009, Progress in Neuro-Psychopharmacology and Biological Psychiatry.