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Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress.
Dorovic, Dorde; Lazarevic, Vesna; Arandelovic, Jovana; Stevanovic, Vladimir; Paslawski, Wojciech; Zhang, Xiaoqun; Velimirovic, Milica; Petronijevic, Natasa; Puskas, Laslo; Savic, Miroslav M; Svenningsson, Per.
Afiliación
  • Dorovic D; Neuro Svenningsson, Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden; Institute of Anatomy "Niko Miljanic", School of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: djordjedjorovic90@gmail.com.
  • Lazarevic V; Neuro Svenningsson, Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Arandelovic J; Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe St, 11000 Belgrade, Serbia.
  • Stevanovic V; Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe St, 11000 Belgrade, Serbia.
  • Paslawski W; Neuro Svenningsson, Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Zhang X; Neuro Svenningsson, Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Velimirovic M; Institute of Clinical and Medical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia.
  • Petronijevic N; Institute of Clinical and Medical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia.
  • Puskas L; Institute of Anatomy "Niko Miljanic", School of Medicine, University of Belgrade, Belgrade, Serbia.
  • Savic MM; Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe St, 11000 Belgrade, Serbia.
  • Svenningsson P; Neuro Svenningsson, Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden.
J Affect Disord ; 349: 286-296, 2024 Mar 15.
Article en En | MEDLINE | ID: mdl-38199412
ABSTRACT

BACKGROUND:

Early life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels.

METHODS:

Male Wistar rats exposed to these stress paradigms were subjected to a comprehensive behavioral analysis. In hippocampal synaptosomes we investigated neurotransmitter release and glutamate concentration. The expression of CaMKII and the content of monoamines were determined in selected brain regions. Brain-derived neurotrophic factor (BDNF) mRNA was quantified by radioactive in situ hybridization.

RESULTS:

We report a distinct behavioral phenotype in the double-hit group. Double-hit and SPS groups had decreased hippocampal presynaptic glutamatergic function. In hippocampus, double-hit stress caused a decrease in autophosphorylation of CaMKII. In prefrontal cortex, both SPS and double-hit stress had a similar effect on CaMKII autophosphorylation. Double-hit stress, rather than SPS, affected the norepinephrine and serotonin levels in prefrontal cortex, and suppressed BDNF gene expression in prefrontal cortex and hippocampus.

LIMITATIONS:

The study was conducted in male rats only. The affected brain regions cannot be restricted to hippocampus, prefrontal cortex and amygdala.

CONCLUSION:

Double-hit stress caused more pronounced and distinct behavioral, molecular and functional changes, compared to MD or SPS alone.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos por Estrés Postraumático / Serotonina / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: J Affect Disord Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos por Estrés Postraumático / Serotonina / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: J Affect Disord Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos