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White Matter Microstructure in Bipolar Disorder Is Influenced by the Interaction between a Glutamate Transporter EAAT1 Gene Variant and Early Stress
- Source :
- Molecular Neurobiology. 56:702-710
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15591182 and 08937648
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....58e9e26416ac38c371dded2a8c573e10