MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Garcia-Garcia AL, 2009 PubMed
Full Info	Garcia-Garcia AL, Elizalde N, Matrov D, Harro J, Wojcik SM, Venzala E et al. Increased vulnerability to depressive-like behavior of mice with decreased expression of VGLUT1. Biol Psychiatry 2009; 66(3): 275-282.

Study

Hypothesis or Background	Many studies link depression to an increase in the excitatory-inhibitory ratio in the forebrain. Presynaptic alterations in a shared pathway of the glutamate/gamma-aminobutyric acid (GABA) cycle may account for this imbalance. Evidence suggests that decreased vesicular glutamate transporter 1 (VGLUT1) levels in the forebrain affect the glutamate/GABA cycle and induce helpless behavior. We studied decreased VGLUT1 as a potential factor enhancing a depressive-like phenotype in an animal model.
Sample Information	mice
Method Detail	Glutamate and GABA synthesis as well as oxidative metabolism were studied in heterozygous mice for the VGLUT1+/- and wildtype. The regulation of neurotransmitter levels, proteins involved in the glutamate/GABA cycle, and behavior by both genotype and chronic mild stress (CMS) were studied. Finally, the effect of chronic imipramine on VGLUT1 control and CMS mice was studied.
Method Keywords	protein analysis; sucrose consumption test; locomotor activity test; forced swimming test; elevated plus maze; Marble Burying Test; novel object recognition test
Result	CMS induced an increase of glutamate and a decrease of GABA, the vesicular GABA transporter (VGAT), and glutamic acid decarboxylase 65 (GAD65) in both areas and led to upregulation of EAAT1 in the hippocampus. Moreover, CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory. VGLUT1+/- CMS mice showed a combined phenotype (genotype plus stress) and specific alterations, such as an upregulation of VGLUT2 and hyperlocomotion. Moreover, an increased vulnerability to anhedonia and helplessness reversible by chronic imipramine was shown.
Conclusions	These studies highlight a crucial role for decreased VGLUT1 in the forebrain as a biological mediator of increased vulnerability to chronic mild stress.

Relationships reported by Garcia-Garcia AL, 2009

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
anhedonic-like behavior from animal model (anhedonic-like behavior)	cognition and behavior	Stress (stress)	environment		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Stress (stress)	environment	Excitatory amino acid transporter 1 (excitatory amino acid transporter 1 (EAAT1))	protein		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
SLC17A7 (vesicular glutamate transporter 1 (VGLUT1))	gene	gamma-Aminobutyric Acid (GABA)	molecule		VGLUT1+/- mice showed decreased GABA	Positive
Stress (stress)	environment	Vesicular inhibitory amino acid transporter (vesicular GABA transporter (VGAT))	protein		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Stress (stress)	environment	Glutamate decarboxylase 2 (glutamic acid decarboxylase 65 (GAD65))	protein		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
SLC17A7 (vesicular glutamate transporter 1 (VGLUT1))	gene	SLC1A3 (excitatory amino acid transporter 1 (EAAT1))	gene		VGLUT1+/- mice showed decreased excitatory amino acid transporter 1 (EAAT1)	Positive
Stress (stress)	environment	Glutamates (glutamate)	molecule		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Stress (stress)	environment	gamma-Aminobutyric Acid (GABA)	molecule		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Hippocampus (hippocampus)	brain morphology and function	Stress (stress)	environment		CMS induced an increase of glutamate and a decrease of GABA, the vesicular GABA transporter (VGAT), and glutamic acid decarboxylase 65 (GAD65) in both areas and led to upregulation of EAAT1 in the hippocampus	Positive
Low self esteem (low self esteem)	symptoms	Stress (stress)	environment		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Feelings of hopelessness, worthlessness, and guilt (helplessness)	symptoms	Stress (stress)	environment		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Learning (impaired learning)	cognition and behavior	Stress (stress)	environment		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive
Memory (impaired memory)	cognition and behavior	Stress (stress)	environment		CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory	Positive