Prenatal treatment with corticosterone via maternal injection induces learning and memory impairments via delaying postsynaptic development in hippocampal CA1 neurons of rats

• Published in: Journal of neuroscience research Vol. 102; no. 4; pp. e25323 - n/a
• Main Authors: Kim, Hye‐Ji, Ko, Eun‐A, Kwon, Oh‐Bin, Jung, Sung‐Cherl
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-04-2024
• Subjects: ADHD; Animals; Attention deficit hyperactivity disorder; Autism; BDNF; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cognitive ability; Corticosterone; Corticosterone - pharmacology; Cortisol; Epigenetics; Excitatory postsynaptic potentials; Female; Glutamatergic transmission; Hippocampus; Hippocampus - metabolism; Hormones; Humans; Hydrocortisone; Hyperactivity; Juveniles; Learning; learning and memory; Long-Term Potentiation; LTP; Maze Learning - physiology; Memory; Memory Disorders - metabolism; Mental disorders; Neurodevelopmental disorders; Neurons; Neurons - metabolism; NMDA receptor; Pathogenesis; Pregnancy; Prenatal experience; Rats; Synaptogenesis; Weaning; ADHD; cortisol; LTP; learning and memory; NMDA receptor; BDNF
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.25323

Previously, we reported that prenatal exposure to high corticosterone induced attention‐deficit hyperactivity disorder (ADHD)‐like behaviors with cognitive deficits after weaning. In the present study, cellular mechanisms underlying cortisol‐induced cognitive dysfunction were investigated using rat pups (Corti.Pups) born from rat mothers that were repetitively injected with corticosterone during pregnancy. In results, Corti.Pups exhibited the failure of behavioral memory formation in the Morris water maze (MWM) test and the incomplete long‐term potentiation (LTP) of hippocampal CA1 neurons. Additionally, glutamatergic excitatory postsynaptic currents (EPSCs) were remarkably suppressed in Corti.Pups compared to normal rat pups. Incomplete LTP and weaker EPSCs in Corti.Pups were attributed to the delayed postsynaptic development of CA1 neurons, showing a higher expression of NR2B subunits and lower expression of PSD‐95 and BDNF. These results indicated that the prenatal treatment with corticosterone to elevate cortisol level might potently downregulate the BDNF‐mediated signaling critical for the synaptic development of hippocampal CA1 neurons during brain development, and subsequently, induce learning and memory impairment. Our findings suggest a possibility that the prenatal dysregulation of cortisol triggers the epigenetic pathogenesis of neurodevelopmental psychiatric disorders, such as ADHD and autism.
Prenatal treatment with corticosterone through maternal injection led to the collapse of postsynaptic development in hippocampal CA1 neurons, resulting in memory impairment. The cellular mechanisms underlying this phenomenon were attributed to the downregulated signaling cascades of BDNF and PSD‐95.