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      Neonatal Tactile Stimulations Affect Genetic Generalized Epilepsy and Comorbid Depression-Like Behaviors

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          Abstract

          Recent studies suggest that development of absence epilepsy and comorbid depression might be prevented by increased maternal care of the offspring, in which tactile stimulation induced by licking/grooming and non-nutritive contact seem to be crucial. In this study, we aimed to evaluate the effect of neonatal tactile stimulations (NTS) on absence epilepsy and depression-like behaviors in adulthood. Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat pups with a genetic predisposition to absence epilepsy were divided into tactile stimulation (TS) group, deep touch pressure (DTP) group, maternal separation (MS) group or control group. Between postnatal day 3 and 21, manipulations (TS, DTP, and MS) were carried out for 15 min and three times a day. Animals were submitted to locomotor activity, sucrose consumption test (SCT) and forced swimming test (FST) at five months of age. At the age of six months, the electroencephalogram (EEG) recordings were conducted in order to quantify the spike-wave discharges (SWDs), which is the hallmark of absence epilepsy. The TS and DTP groups showed less and shorter SWDs in later life in comparison to maternally separated and control rats. SWDs’ number and total duration were significantly reduced in TS and DTP groups whereas mean duration of SWDs was reduced only in DTP group ( p < 0.05). TS and DTP also decreased depression-like behaviors measured by SCT and FST in adult animals. In the SCT, number of approaches was significantly higher in TS and DTP groups than the maternally separated and control rats. In the FST, while the immobility latency of TS and DTP groups was significantly higher, only TS group showed significantly decreased immobility and increased swimming time. The results showed that NTS decreases both the number and length of SWDs and the depression-like behaviors in WAG/Rij rats probably by increasing arousal level and causing alterations in the level of some neurotrophic factors as well as in functions of the neural plasticity in the developing rat’s brain.

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          The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity.

          Recent evidence suggests that neuronal plasticity plays an important role in the recovery from depression. Antidepressant drugs and electroconvulsive shock treatment increase the expression of several molecules, which are associated with neuronal plasticity, in particular the neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some cases these neurodegenerative signs can be attenuated by successful treatment. Such observations suggest a central role for neuronal plasticity in depression and the antidepressant effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which, under appropriate environmental guidance, leads to the rewiring of a developmentally dysfunctional neural network. These observations suggest that the simple form of the neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support underlies mood disorders and increases in these neurotrophic factors to normal levels brings about mood recovery, may not sufficiently explain the complex process of recovery from depression. This review discusses recent data on the role of BDNF and its receptors in depression and the antidepressant response and suggests a model whereby the effects of antidepressant treatments could be explained by a reactivation of activity-dependent and BDNF-mediated cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to environmental challenges.
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            Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease.

            Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that regulates diverse developmental events from the selection of neural progenitors to the terminal dendritic differentiation and connectivity of neurons. We focus here on activity-dependent synaptic regulation by BDNF and its receptor, full length TrkB. BDNF-TrkB signaling is involved in transcription, translation, and trafficking of proteins during various phases of synaptic development and has been implicated in several forms of synaptic plasticity. These functions are carried out by a combination of the three signaling cascades triggered when BDNF binds TrkB: The mitogen-activated protein kinase (MAPK), the phospholipase Cgamma (PLC PLCgamma), and the phosphatidylinositol 3-kinase (PI3K) pathways. MAPK and PI3K play crucial roles in both translation and/or trafficking of proteins induced by synaptic activity, whereas PLCgamma regulates intracellular Ca(2+) that can drive transcription via cyclic AMP and a protein kinase C. Conversely, the abnormal regulation of BDNF is implicated in various developmental and neurodegenerative diseases that perturb neural development and function. We will discuss the current state of understanding BDNF signaling in the context of synaptic development and plasticity with a focus on the postsynaptic cell and close with the evidence that basic mechanisms of BDNF function still need to be understood to effectively treat genetic disruptions of these pathways that cause devastating neurodevelopmental diseases.
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              BDNF and activity-dependent synaptic modulation.

              Bai Lu (2003)
              It is widely accepted that neuronal activity plays a pivotal role in synaptic plasticity. Neurotrophins have emerged recently as potent factors for synaptic modulation. The relationship between the activity and neurotrophic regulation of synapse development and plasticity, however, remains unclear. A prevailing hypothesis is that activity-dependent synaptic modulation is mediated by neurotrophins. An important but unresolved issue is how diffusible molecules such as neurotrophins achieve local and synapse-specific modulation. In this review, I discuss several potential mechanisms with which neuronal activity could control the synapse-specificity of neurotrophin regulation, with particular emphasis on BDNF. Data accumulated in recent years suggest that neuronal activity regulates the transcription of BDNF gene, the transport of BDNF mRNA and protein into dendrites, and the secretion of BDNF protein. There is also evidence for activity-dependent regulation of the trafficking of the BDNF receptor, TrkB, including its cell surface expression and ligand-induced endocytosis. Further study of these mechanisms will help us better understand how neurotrophins could mediate activity-dependent plasticity in a local and synapse-specific manner.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                23 July 2020
                2020
                : 14
                : 132
                Affiliations
                Department of Physiology, Faculty of Medicine, Kocaeli University , Kocaeli, Turkey
                Author notes

                Edited by: Simona Cabib, Sapienza University of Rome, Italy

                Reviewed by: Michael Fritz, Linköping University, Sweden; Marilise Escobar Burger, Federal University of Santa Maria, Brazil

                *Correspondence: Aymen Balikci, pt_eymen@ 123456hotmail.com

                These authors have contributed equally to this work

                This article was submitted to Pathological Conditions, a section of the journal Frontiers in Behavioral Neuroscience

                Article
                10.3389/fnbeh.2020.00132
                7390910
                ede9e007-e694-43d3-9d03-44c65d10e647
                Copyright © 2020 Balikci, Ilbay and Ates.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 May 2020
                : 02 July 2020
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 76, Pages: 13, Words: 0
                Categories
                Neuroscience
                Original Research

                Neurosciences
                absence epilepsy,depression,handling,maternal separation,neonatal tactile stimulation,wag/rij rat

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