title: Early-life stress affects the structural and functional plasticity of the medial prefrontal cortex in adolescent rats.
abstract: Early life experiences are crucial factors that shape brain development and function due to their ability to induce structural and functional plasticity. Among these experiences, early-life stress (ELS) is known to interfere with brain development and maturation, increasing the risk of future psychopathologies, including depression, anxiety, and personality disorders. Moreover, ELS may contribute to the emergence of these psychopathologies during adolescence. In this present study, we investigated the effects of ELS, in the form of maternal separation (MS), on the structural and functional plasticity of the medial prefrontal cortex (mPFC) and anxiety-like behavior in adolescent male rats. We found that the MS procedure resulted in disturbances in mother-pup interactions that lasted until weaning and were most strongly demonstrated by increases in nursing behavior. Moreover, MS caused atrophy of the basal dendritic tree and reduced spine density on both the apical and basal dendrites in layer II/III pyramidal neurons of the mPFC. The structural changes were accompanied by an impairment of long-term potentiation processes and increased expression of key proteins, specifically glutamate receptor 1, glutamate receptor 2, postsynaptic density protein 95, αCa(2+) /calmodulin-dependent protein kinase II and αCa(2+)/calmodulin-dependent protein kinase II phosphorylated at residue Thr305, that are engaged in long-term potentiation induction and maintenance in the mPFC. We also found that the MS animals were more anxious in the light/dark exploration test. The results of this study indicate that ELS has a significant impact on the structural and functional plasticity of the mPFC in adolescents. ELS-induced adaptive plasticity may underlie the pathomechanisms of some early-onset psychopathologies observed in adolescents.
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. chocyk@if-pan.krakow.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chocyk
authors.forename: Bartosz
authors.initials: B
authors.lastname: Bobula
authors.forename: Dorota
authors.initials: D
authors.lastname: Dudys
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Przyborowska
authors.forename: Iwona
authors.initials: I
authors.lastname: Majcher-Maślanka
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Hess
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wędzony
mesh_terms: D000367:Age Factors; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D049229:Dendritic Spines / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D005106:Exploratory Behavior; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation; D008297:Male; D008425:Maternal Behavior; D008426:Maternal Deprivation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; C501449:Dlg4 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptors; Ca2+/calmodulin-dependent protein kinase II; long-term potentiation; maternal separation; postsynaptic density protein 95