White Matter Microstructure in Bipolar Disorder Is Influenced by the Interaction between a Glutamate Transporter EAAT1 Gene Variant and Early Stress
| Autor: | Cristina Colombo, Sara Poletti, Francesco Benedetti, S. Brioschi, Cristina Lorenzi, Alessandro Serretti, Alice Vitali, Irene Bollettini |
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| Přispěvatelé: | Poletti S., Bollettini I., Lorenzi C., Vitali A., Brioschi S., Serretti A., Colombo C., Benedetti F., Poletti, Sara, Bollettini, Irene, Lorenzi, Cristina, Vitali, Alice, Brioschi, Silvia, Serretti, Alessandro, Colombo, Cristina, Benedetti, Francesco |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Bipolar Disorder EAAT2 Bipolar disorder SLC1A2 Central nervous system Neuroscience (miscellaneous) Polymorphism Single Nucleotide White matter 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic Imaging Three-Dimensional 0302 clinical medicine Adverse Childhood Experiences Internal medicine medicine Extracellular Humans biology Chemistry Glutamate receptor Neurotoxicity Middle Aged medicine.disease White Matter Adverse childhood experience TBSS Excitatory Amino Acid Transporter 1 030104 developmental biology medicine.anatomical_structure Endocrinology Neurology biology.protein Excitatory postsynaptic potential Female Glial glutamate transporter 030217 neurology & neurosurgery Human |
| Zdroj: | Molecular Neurobiology. 56:702-710 |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-018-1117-6 |
| Popis: | Glutamate is the principal excitatory neurotransmitter in the central nervous system. In mature brains, it is critically involved in neuroplasticity and, at high levels, neurotoxicity. The concentrations of glutamate in the extracellular space are maintained at low physiological levels by molecular glutamate transporters (excitatory amino acid transporters-EAATs). Adverse childhood experiences (ACEs) are highly reported in bipolar disorder (BD) and interact with the glutamatergic system in the brain. The aim of the study is to investigate the effect of a glutamate transporter polymorphism EAAT2-181A > C (rs4354668) and exposure to ACE on white matter microstructure in patients with BD. We assessed 175 bipolar subjects using diffusion tensor imaging, Risky Families Questionnaire, and EEAT2 rs4354668 variants. We observed an interaction between ACE and rs4354668: carriers of the G allele showed lower axial diffusivity compared to T/T homozygotes when exposed to high stress and higher axial diffusivity than T/T when exposed to low stress. Since the mutant G allele has been associated with a reduced transcriptional activity and expression of the transporter protein, and early stress is associated with a reduced expression of the EAAT2, we could hypothesize that after exposure to high levels of ACE G/G homozygotes are more vulnerable to stress reporting the highest damage as a consequence of an excess of free glutamate. |
| Databáze: | OpenAIRE |
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