Effects of Neonatal Undernutrition on Development of the Dorsolateral Prefrontal Cortex Pyramidal Cells in the Rat

DOI: 10.4236/jbbs.2014.41007   PDF   HTML   XML   3,584 Downloads   5,074 Views   Citations


The dorsolateral prefrontal cortex (dlPFC) of the rat plays a role in the encoding of neuronal signals involved in conflict-induced behavioral adjustment, working memory, planning and executive abilities, attentional control and other cognitive responses. In altricial species, early perinatal undernutrition interferes with the morphofunctional organization of a number of central nervous system (CNS) structures including the prefrontal cortex. The effects of neonatal undernutrition on dendritic arbor density, perikaryon measurements, and the number of spines (detected by rapid-Golgi) of basilar dendritic segments in layer III pyramidal neurons of the dlPFC were examined in male Wistar rats on postnatal (PDs) 12, 20, and 30. In the underfed (U) subjects the distal portions of the dendritic arbors had a consistent hipoplasia, mainly on PD 30, with reduced cross sectional area, perimeter, and spine densities on the basilar dendrites on all days studied. Thus, the alterations of the dlPFC pyramidal neurons may interfere with the plastic synaptic activity and cognitive performance of rats subjected to the stress of early underfeeding. Characterizing these anatomical alterations may help to understand the disrupted cognitive processes associated with neonatal undernutrition.

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C. Torrero, M. Regalado, L. Rubio and M. Salas, "Effects of Neonatal Undernutrition on Development of the Dorsolateral Prefrontal Cortex Pyramidal Cells in the Rat," Journal of Behavioral and Brain Science, Vol. 4 No. 1, 2014, pp. 49-57. doi: 10.4236/jbbs.2014.41007.

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The authors declare no conflicts of interest.


[1] [1] D. A. Callison and J. W. Spencer, “Effect of Chronic Undernutrition and/or Visual Deprivation Upon the Visual Evoked Potential from the Developing Rat Brain,” Developmental Psychobiology, Vol. 1, No. 3, 1968, pp. 196-204. http://dx.doi.org/10.1002/dev.420010308
[2] N. M. Bass, M. G. Netsky and E. Young, “Effect of Neonatal Malnutrition on Developing Cerebrum. 1. Microchemical and Histologic Study of Cellular Differentiation in the Rat,” Archives of Neurology (Chic), Vol. 23, No. 4, 1970, pp. 289-302.
[3] B. M. Lester, R. E. Klein and S. J. Martinez, “The Use of Habituation in the Study of the Effects of Infantile Malnutrition,” Developmental Psychobiology, Vol. 8, No. 6, 1975, pp. 541-546.
[4] J. L. Smart, “Maternal Behaviour of Undernourished Mother Rats toward Well Fed and Underfed Young,” Physiology and Behavior, Vol. 16, No. 2, 1976, pp. 147-149.
[5] A. Hernandez, S. Ruiz, H. Perez and R. Soto-Moyano, “Effect of Early Malnutrition on Dynamic Properties of Axodendritic Synapses in the Rat Prefrontal Cortex,” Journal of Neurobiology, Vol. 16, No. 5, 1985, pp. 389-393 http://dx.doi.org/10.1002/neu.480160505
[6] L. F. Campbell and K. S. Bedi, “The Effects of Undernutrition during Early Life on Spatial Learning,” Physiology and Behavior, Vol. 45, No. 5, 1989, pp. 883-890.
[7] C. Escobar and M. Salas, “Neonatal Under-nutrition and Amygdaloid Nuclear Complex Development: An Experimental Study in the Rat,” Experimental Neurology, Vol. 122, No. 2, 1993, pp. 311-318.
[8] E. Susser, R. Neugebauer, H. W. Hoek, A. S. Brown, S. Lin, D. Labovitz and J. M. Gorman, “Schizophrenia after Prenatal Femine. Further Evidence,” Archives General Psychiatry, Vol. 53, No. 1, 1996, pp. 25-31.
[9] W. E. Bunney and B. G. Bunney, “Evidence for a Compromised Dorsolateral Prefrontal Cortical Parallel Circuit in Schizophrenia,” Brain Research Reviews, Vol. 31, No. 2-3, 2000, pp. 138-146.
[10] Y. Goto and A. A. Grace, “Dopaminergic Modulation of Limbic and Cortical Drive of Nucleus Accumbens in Goal-Directed Behavior,” Nature Neuroscience, Vol. 8, No. 6, 2005, pp. 805-812.
[11] M. Salas, “Effects of Early Undernutrition on Dendritic Spines of Cortical Pyramidal Cells in the Rat,” Developmental Neuroscience, Vol. 3, No. 3, 1980, pp. 109-117.
[12] J. W. Brock and C. Prasad, “Alterations in Dendritic Spine Density in the Rat Brain Associated with Protein Malnu-trition,” Developmental Brain Research, Vol. 66, No. 2, 1992, pp. 266-269.
[13] L. J. Garey, W. Y. Ong, T. S. Patel, M. Kanani, A. Davis, A. M. Mortimer, T. R. E. Barnes and S. R. Hirsch, “Reduced Dendritic Spine Density on Cerebral Cortical Pyramidal Neurons in Schizophrenia,” Journal of Neurology Neurosurgery Psychiatry, Vol. 65, No. 4, 1998, pp. 446-453. http://dx.doi.org/10.1136/jnnp.65.4.446
[14] L. A. Glantz and D. A. Lewis, “Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia,” Archives Genetics Psychiatry, Vol. 57, No. 1, 2000, pp. 65-73.
[15] M. S. Murmu, S. Salomon, Y. Biala, M. Weinstock, K Braun and J. Bock, “Changes of Spine Density and Dendritic Complexity in the Prefrontal Cortex in Offspring of Mothers Exposed to Stress during Pregnancy,” European Journal of Neuroscience, Vol. 24, No. 5, 2006, pp. 1477-1487.
[16] M. Salas, S. Diaz and A. Nieto, “Effects of Neonatal Food Deprivation on Cortical Spines and Dendritic Development of the Rat,” Brain Research, Vol. 73, No. 1, 1974, pp. 139-144.
[17] B. A. Brody and K. H. Pribram, “The Role of Frontal and Parietal Cortex in Cognitive Processing: Tests of Spatial and Sequence Functions,” Brain, Vol. 101, No. 4, 1978, pp. 607-633. http://dx.doi.org/10.1093/brain/101.4.607
[18] H. Perez, S. Ruiz, A. Hernandez and R. Soto-Moyano, “Effect of Early Undernutrition on Reactivity of the Rat Parietal Association Area,” Experimental Neurology, Vol. 82, No. 1, 1983, pp. 241-244.
[19] M. R. Rosenzweigh and E. L. Bennett, “Psychobiology of Plasticity: Effects of Training and Experience on Brain and Behavior,” Behavioral Brain Research, Vol. 78, No. 1, 1996, pp. 57-65.
[20] A. S. Fleming, D. H. O’Day and G. W. Kraemer, “Neurobiology of Mother-Infant Interactions: Experience and Central Nervous System Plasticity across Development and Generations,” Neuroscience Biobehavioral Reviews, Vol. 23, No. 5, 1999, pp. 673-685.
[21] S. Macri and H. Würbel, “Developmental Plasticity of HPA and Fear Responses in Rats: A Critical Review of the Maternal Mediation Hypothesis,” Hormones and Behavior, Vol. 50, No. 5, 2006, pp. 667-680.
[22] M. Salas, C. Torrero and S. Pulido, “Long-Term Alterations in the Maternal Behavior of Neonatally Under-nourished Rats,” Physiology and Behavior, Vol. 33, No. 2, 1984, pp. 273-278.
[23] M. Meaney, J. Dioro, D. Francis, J. Woddowson, P. La Plante, C. Caldji, S. Sharma, J. R. Seckl and P. M. Plotsky, “Early Environmental Regulation of Forebrain Glucocorticoid Receptor Gene Expression: Implications for Adrenocortical Responses to Stress,” Developmental Neuroscience, Vol. 18, No. 1-2, 1996, pp. 49-72.
[24] M. Salas, C. Torrero, M. Regalado and E. Perez, “Retrieving of Pups by Neonatally Stressed Mothers,” Nutritional Neuroscience, Vol. 5, No. 6, 2002, pp. 399-405.
[25] M. Leonhardt, S. G. Mathhews, M. J. Meaney and C. D. Walker, “Psychological Stressors as a Model of Maternal Adversity: Diurnal Modulation of Corticosterone Responses and Changes in Maternal Behavior,” Hormones and Behavior, Vol. 51, No. 1, 2007, pp. 77-88.
[26] J. Leah, H. Allardyce and H. Cummins, “Evoked Cortical Potentials Correlates of Rearing Environments in Rats,” Biology Psychology, Vol. 20, No. 1, 1985, pp. 21-29.
[27] J. Bock, M. Gruss, S. Becker and K. Braun, “Experience-Induced Changes of Dendritic Spine Densities in Prefrontal and Sensory Cortex: Correlation with Developmental Time Windows,” Cerebral Cortex, Vol. 15, No. 6, 2005 pp. 802-808.
[28] R. Pascual and S. P. Zamora-Leon, “Effects of Neonatal Maternal Deprivation and Postweaning Environmental Complexity on Dendritic Morphology of Prefrontal Pyramidal Neurons in the Rat,” Acta Neurobiologiae Expermentalis (Wars), Vol. 67, No. 4, 2007. pp. 471-479.
[29] E. Monroy, E. Hernandez-Torres and G. Flores, “Maternal Separation Disrupts Dendritic Morphology of Neurons in Prefrontal Cortex, Hippocampus, and Nucleus Accumbens in Male Rat Offspring,” Journal of Chemical Neuroanatomy, Vol. 40, No.2, 2010, pp. 93-110.
[30] S. Crnic, J. M. Bell, R. Mangold, M. Gruenthal, M. J. Eiler and S. Finger, “Separation-Induced Early Malnutrition: Maternal, Physiological and Behavioral Effects,” Physiology and Behavior, Vol. 26, No. 4, 1981, pp. 695- 707. http://dx.doi.org/10.1016/0031-9384(81)90147-5
[31] National Research Council, “Guidelines for the Care and use of mammals,” In: National Research Council of the National Academies Neuroscience and Behavioral Research. National Academies Press, Washington DC, 2003, p. 209.
[32] J. G. Vanderbergh, “Prenatal Hormone Exposure and Sexual Variation,” American Scientist, Vol. 91, No. 3, 2003, pp. 218-225. http://dx.doi.org/10.1511/2003.3.218
[33] M. H. S. Lee and D. I. Williams, “Changes in Licking Behaviour of Rat Mother Following Handling of Young,” Animal Behaviour, Vol. 22, No. 3, 1974, pp. 679-681.
[34] C. R. Pryce, D. Bettschen and D. Feldon, “Comparison of the Effects of Early Handling and Early Deprivation on Maternal Care in the Rat,” Developmental Psychobiology, Vol. 38, No. 4, 2001, pp. 239-251.
[35] S. Macri, G. J. Mason and H. Würbel, “Dissociation in the Effects of Neonatal Maternal Separations on Maternal Care and the Offspring’s HPA and Fear Responses in Rats,” European Journal of Neurosciences, Vol. 20, No. 4, 2004, pp. 1017-1024.
[36] J. Altman and S. A. Bayer, “Atlas of Prenatal Rat Brain Development,” CRC Press, Boca Raton, 1995.
[37] A. Lynch, “Postnatal Undernutrition: An Alternative Method,” Developmental Psychobiology, Vol. 9, No. 1, 1976, pp. 39-48. http://dx.doi.org/10.1002/dev.420090107
[38] M. E. Scheibel and A. B. Scheibel, “Structural Substrates for Integrative Patterns in the Brain Stem Reticular Core,” In: H. H. Jasper, et al., Eds., Reticular Formation of the Brain, Little Brown, Boston, 1958, pp. 31-55.
[39] G. Paxinos and C. Watson, “The Rat Brain in Stereotaxic Coordinates,” Academic Press Inc., San Diego, 1986.
[40] D. A. Sholl, “The Organization of the Cerebral Cortex,” Halfner, New York, 1956.
[41] J. Tonkiss, K. Hosokawa, K. Yabusaki and T. Obinata, “Ultrasonic Call Characteristics of Rat Pups Are Altered following Prenatal Malnutrition,” Developmental Psychobiology, Vol. 43, No. 2, 2003, pp. 90-101.
[42] C. M. Khum, S. R. Butler and S. M. Schanbergh, “Selective Depression of Serum Growth Hormone during Maternal Deprivation in Rat Pups,” Science, Vol. 201, No. 4360, 1978, pp. 1034-1036.
[43] G. E. Evoniuk, C. M. Kuhn and S. M. Schanbergh, “The Effect of Tactile Stimulation on Serum Growth Hormone and Tissue Ornithine Decarboxylase Activity during Maternal Deprivation in Rat Pups,” Communications in Psychopharmacology, Vol. 3, No. 5, 1979, pp. 363-370.
[44] S. M. Schanbergh, G. E. Evoniuk and C. M. Kuhn, “Tactile and Nutritional Aspects of Maternal Care: Specific Regulators of Neuroendocrine Function and Cellular Development,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 175, No. 2, 1984, pp.135-146. http://dx.doi.org/10.3181/00379727-175-41779
[45] J. M. Ketelslegers, D. Maiter, M. Maes, L. E. Underwood and J. P. Thissen, “Nutritional Regulation of the Growth Hormone and Insulin-Like Growth-Binding Proteins,” Hormone Research, Vol. 45, No. 3-5, 1996, pp. 252-257. http://dx.doi.org/10.1159/000184797
[46] J. E. Krettek and J. L. Price, “The Cortical Projections of the Mediodorsal Nucleus and Adjacent Thalamic Nuclei in the Rat,” Journal of Comparative Neurology, Vol. 171, No. 2, 1977, pp. 157-191.
[47] R. M. Sullivan and W. G. Brake, “What the Rodent Prefrontal Cortex can Teach us about Attention-Deficit/Hyper-activity Disorder: The Critical Role of Early Developmental Events on Prefrontal Function,” Behavioral Brain Research, Vol. 146, No. 1-2, 2003, pp. 43-55.
[48] L. Lacroix, S. Spinelli, A. Christian and J. Feldon, “Differential Role of the Medial and Lateral Prefrontal Cortices in Fear and Anxiety,” Behavioral Neuroscience, Vol. 114, No. 6, 2000, pp. 1119-1130.
[49] E. G. Curtis, K. Sung-Jae and J. M. Rogers, “Maternal Influences and Epigenetic Programming of the Developing Hypothalamic-Pituitary-Adrenal Axis,” Birth Defects Research Part A, Vol. 91, No. 8, 2011, pp. 797-805.
[50] C. Caldji, B. Tannebaum, S. Sharma, D. Francis, P. M. Plotsky and M. J. Meaney, “Maternal Care during Infancy Regulates the Development of Neural Systems Mediating the Expression of Fearfulness in the Rat,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 9, 1998, pp. 5335-5340.
[51] S. Moriceau and R. M. Sullivan, “Maternal Presence Serves as a Switch between Learning Fear and Attraction in Infancy,” Nature Neuroscience, Vol. 9, No 8, 2006, pp. 1004-1006. http://dx.doi.org/10.1038/nn1733
[52] J. E. Markham and J. I. Koening, “Prenatal Stress: Role in Psychiatric and Depressive Diseases,” Psychopharmacology, Vol. 214, No. 1, 2011, pp. 89-106.
[53] M. Salas and L. Cintra, “Influence of Early Food Restriction on the Responsiveness to Novel Stimuli in Adult Rats,” Boletín de Estudios Médicos y Biológicos, México, Vol. 30, No. 1, 1979, pp. 201-204.
[54] S. S. Almeida, R. A. Garcia and L. M. de Olveira, “Effects of Early Protein Malnutrition and Repeated Testing upon Locomotor and Exploratory Behaviors in the Elevated Plus-Maze,” Physiology and Behavior, Vol. 54, No. 4, 1993, pp. 749-752.
[55] R. Bousalham, B. Benazzoouz, A. El Hessni, A. Ouichou and A. Mesfioui, “Maternal Separation Affects Mothers’ Affective and Reproductive Behaviors as Well as Second Offspring’s Emotionality,” Journal of Behavioural and Brain Science, Vol. 3, No. 5, 2013, pp. 409-414.
[56] S. M. Schanberg, V. F. Ingledue, J. Y. Lee, Y. A. Hannun and J. V. Bartolome, “PKC Alpha Mediates Maternal Touch Regulation of Growth-Related Gene Expression in Infant Rats,” Neuropsychopharmacology, Vo. 28, No. 6, 2003, pp. 1026-1030.
[57] B. Coupé, I. Dutriez-Casteloot, C. Breton, F. Lefévre, J. Mairesse, A. Dickes-Coopman, M. Silhol, L. Tapia-Arancibia, J. Lesage and D. Vieau, “Perinatal Undernutrition Modifies Cell Proliferation and Brain-Derived Neurotro- phic Factor Levels during Critical Time-Windows for Hypothalamic and Hippocampal Development in the Male Rat,” Journal of Neuroendo-crinology, Vol. 21. No. 1, 2009, pp. 40-48.
[58] L. Ciani, K. A, Boyle, E. Dickins, M. Sahores, D. Anane, D. M. Lopes, A. J. Gibb and P. C. Salinas, “Wnt7 Signaling Promotes Dendritic Spine Growth and Synaptic Strengh through Ca2+ /Calmodulin-Dependent Protein Kinase II,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 26, 2011, pp. 10732-10737. http://dx.doi.org/10.1073/pnas.1018132108

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