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The Role of Adult Neurogenesis in Psychiatric and Cognitive Disorders

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The Role of Adult Neurogenesis in Psychiatric and Cognitive Disorders BRES : 44678 Model7 pp: À 129ðcol:fig: : NILÞ brain research ] ( ]]]]) ]]]– ]]] Available online at www.sciencedirect.com 121 122 123 124 125 126 www.elsevier.com/locate/brainres 127 128 129 Review 130 131 132 The role of adult neurogenesis in psychiatric 133 134 Q2 and cognitive disorders 135 136 Deana M Applen, Rene Solano Fonseca, Erzsebet Kokovay 137 Q1 138 University of Texas Health Science Center at San Antonio, Department of Cellular and Structural Biology, 7703, Floyd 139 Curl Drive, San Antonio, TX 78229, United States 140 141 142 article info abstract 143 144 Article history: Neurogenesis in mammals occurs throughout life in two brain regions: the ventricular– Q3 145 Accepted 13 January 2016 subventricular zone (V–SVZ) and the subgranular zone (SGZ) of the hippocampal dentate 146 gyrus. Development and regulation of the V–SVZ and SGZ is unique to each brain region, 147 Keywords: but with several similar characteristics. Alterations to the production of new neurons in 148 Adult Neurogenesis neurogenic regions have been linked to psychiatric and neurodegenerative disorders. 149 Ventricular–Subventricular Zone Decline in neurogenesis in the SGZ correlates with affective and psychiatric disorders, and 150 Subgranular Zone can be reversed by antidepressant and antipsychotic drugs. Likewise, neurogenesis in the – 151 Neurotransmitters V SVZ can also be enhanced by antidepressant drugs. The regulation of neurogenesis by 152 Psychiatric Disorders neurotransmitters, particularly monoamines, in both regions suggests that aberrant 153 neurotransmitter signaling observed in psychiatric disease may play a role in the 154 pathology of these mental health disorders. Similarly, the cognitive deficits that accom- 155 pany neurodegenerative disease may also be exacerbated by decreased neurogenesis. This 156 review explores the regulation and function of neural stem cells in rodents and humans, 157 and the involvement of factors that contribute to psychiatric and cognitive deficits. 158 This article is part of a Special Issue entitled SI:StemsCellsinPsychiatry. 159 & 2016 Published by Elsevier B.V. 160 161 162 163 181 164 Contents 182 165 183 166 1. Introduction. ................................................................................... 2 184 167 2. Neural stem cell developmental origins and lineage .................................................... 2 185 168 3. Factors regulating neurogenesis . ................................................................. 3 186 169 4. Neurotransmitter regulation of neurogenesis .......................................................... 4 187 170 4.1. Neurotransmitter regulation of stem cells in the SGZ . ............................................4 188 171 4.2. Neurotransmitter regulation of stem cells in the V–SVZ.............................................4 189 172 4.3. Antidepressant drug actions in neurogenic regions .................................................5 190 173 5. Neurogenesis in humans. ....................................................................... 6 191 174 192 175 n 193 176 Corresponding author. Tel.: þ210 567 0725. 194 177 E-mail address: [email protected] (D. Apple). 195 178 http://dx.doi.org/10.1016/j.brainres.2016.01.023 196 179 & 0006-8993/ 2016 Published by Elsevier B.V. 197 180 Please cite this article as: Apple, D.M, et al., The role of adult neurogenesis in psychiatric and cognitive disorders. Brain Research (2016), http://dx.doi.org/10.1016/j.brainres.2016.01.023 BRES : 44678 2 brain research ] ( ]]]]) ]]]– ]]] 198 6. Adult human neurogenesis and psychiatric disorders ................................................... 7 258 199 7. Conclusions and future perspectives. ............................................................... 7 259 200 Author information ................................................................................. 7 260 201 Acknowledgments . ................................................................................. 7 261 202 References . ....................................................................................... 7 262 203 263 204 264 205 1. Introduction rise to type C transit amplifying cells which in turn give rise 265 – 206 to type A neuroblasts. Neuroblasts then exit the V SVZ and 266 207 Neurogenesis is the process of producing new neurons from undergo extensive migration through the rostral migratory 267 208 neural stem cells (NSCs). In most brain regions, this process is stream to arrive at the olfactory bulb, where they mature into 268 209 restricted to a limited period during development, and ends GABAeric interneurons, many of which also express dopa- 269 210 shortly after birth (Gotz and Huttner, 2005; Ming and Song, mine (Alvarez-Buylla et al., 2001; Doetsch and Alvarez-Buylla, 270 211 2011; Taverna et al., 2014). However, neurogenesis is observed 1996; Doetsch et al., 1997; Ming and Song, 2011). The spatial 271 212 well into the postnatal period and throughout adulthood organization of these newborn neurons in the olfactory bulb 272 – 213 primarily in two discrete brain regions: the subgranular zone is dependent upon the location of their origin in the V SVZ, 273 – 214 (SGZ) of the dentate gyrus and the ventricular–subventricular and NSCs originating from different V SVZ microdomains 274 215 zone (V–SVZ), which lines the lateral wall of the lateral produce interneuron populations with distinct molecular 275 216 ventricles. The process of neurogenesis has been linked markers in the olfactory bulb (Merkle et al., 2014). NSCs also 276 217 behaviorally and biochemically to psychiatric disorders such give rise to oligodendrocytes and astrocytes (Doetsch et al., 277 218 as major depression, schizophrenia, and cognitive dysfunc- 2002; Lois and Alvarez-Buylla, 1993; McKay, 1997; Merkle 278 219 tion. The neurogenic cells of the hippocampus are commonly et al., 2004) however the lineage for these cells is less clear. 279 – 220 linked to psychiatric disorders, and neurogenesis is thought NSCs are tightly regulated by the niche which in the V SVZ is 280 221 to be required for a therapeutic response to antidepressant bordered on one side by ciliated ependymal cells lining the 281 222 treatment. However, neural stem cells in the V–SVZ have also lateral ventricle and on the striatal side by a vast vascular 282 223 displayed changes in function and number in psychiatric plexus. Type B NSCs span these two compartments sending 283 224 disease, age, and with increased stress levels, which are often an apical process through the ependymal layer into the 284 225 a precipitating factor in the onset of psychiatric disorders. lateral ventricle and a basal process contacting blood vessels 285 226 NSCs have been shown to respond to treatment with anti- which allows NSCs to receive molecular signals from cere- 286 fl 227 depressant and atypical antipsychotic drugs, which can brospinal uid (Kokovay et al., 2012; Sawamoto et al., 2006), 287 228 rescue diminished neurogenesis. The functional implications ependymal cells (Lim et al., 2000) and the vasculature 288 229 of decreased neurogenesis in psychiatric disease, as well as (Delgado et al., 2014; Kokovay et al., 2010; Shen et al., 2008; 289 230 the therapeutic implications of rescuing neurogenesis with Tavazoie et al., 2008). In addition to type B NSCs, microglia, 290 231 interventions, remain unclear. The emerging links between niche astrocytes, type C, and type A cells are closely 291 – 232 neurogenesis and mental health disorders support the idea assembled in the V SVZ niche between the vasculature and 292 233 that neurogenic therapies may one day enhance less effective ependymal layer. 293 234 treatments for patients suffering from major depression, In the hippocampus, type 1 NSCs are mostly quiescent, 294 235 schizophrenia, cognitive decline, and neurodegeneration. with their cell bodies in the SGZ and processes extending 295 236 Here, we provide an overview of neurogenesis in the SGZ through the granular cell layer, and a tangential process 296 237 and V–SVZ, and explore the current literature on the relation- extending through the border of the hilus and the granular 297 238 ship between psychiatric disorders, therapeutics, and adult cell layer similar to radial glia (Seri et al., 2004). Two sex 298 þ 239 neurogenesis. determining region Y-box 2 (Sox-2) populations of progeni- 299 240 tor cells are present in the hippocampus: a quiescent radial 300 241 glia-like subpopulation expressing GFAP, nestin, and brain- 301 242 2. Neural stem cell developmental origins and lipid binding protein (BLBP), and a non-radial glia-like sub- 302 243 lineage population that is more proliferative and lacks the markers 303 244 associated with radial glia (Suh et al., 2007). Once activated, 304 245 Much of our understanding of adult NSC biology has come NSCs divide asymmetrically, giving rise to a type 2 daughter 305 246 from studies in rodents, which have shown that NSCs in the cell. type 2 cells are amplifying neural progenitor cells that 306 247 SGZ and the V–SVZ share many similarities but are two lack the GFAP expression of the type 1 mother cell, but retain 307 248 distinct populations of cells that differ significantly in their expression of Nestin (Encinas et al., 2006; Filippov et al., 2003; 308 249 development, organization, and function. NSCs from both the Kempermann et al., 2004). These progenitor cells proliferate 309 250 V–SVZ and SGZ are astrocyte-like cells with morphological in close association with astrocytes and the vasculature in 310 251 similarity to mature
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