Regulation of markers of synaptic function in mouse models of depression: chronic mild stress and decreased expression of VGLUT1.
Depression has been linked to failure in synaptic plasticity originating from environmental and/or genetic risk factors. The chronic mild stress model regulates the expression of synaptic markers of neurotransmitter function and associated depressive-like behaviour. Moreover, mice heterozygous for the synaptic vesicle protein vesicular glutamate transporter 1 (VGLUT1), have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour. Here, we aimed to identify, in these two experimental models, mechanisms of failure in synaptic plasticity, common to stress and impaired glutamate function. First, we show that chronic mild stress induced a transient decrease of different plasticity markers (VGLUT1, synapsin 1, sinaptophysin, rab3A and activity regulated cytoskeletal protein - Arc) but a long-lasting decrease of the brain derived neurotrophic factor as well as depressive-like behaviour. The immediate early gene Arc was also down-regulated in VGLUT1+/- heterozygous mice. In contrast, an opposite regulation of synapsin 1 was observed. Finally, both models showed a marked increase of cortical Arc response to novelty. Increased Arc response to novelty could be suggested as a molecular mechanism underlying failure to adapt to environmental changes, common to chronic stress and altered glutamate function. Further studies should investigate whether these changes are associated to depressive-like behaviour both in animal models and in depressed patients.
Elizalde
Natalia
N
Department of Pharmacology, University of Navarra, Pamplona, Spain.
Pastor
Pedro M
PM
Garcia-García
Alvaro L
AL
Serres
Florance
F
Venzala
Elisabet
E
Huarte
Judit
J
Ramírez
Maria Javier
MJ
Del Rio
Joaquín
J
Sharp
Trevor
T
Tordera
Rosa M
RM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009433:Neural Inhibition / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D011897:Random Allocation; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics
D015415:Biomarkers; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D050598:Vesicular Glutamate Transport Protein 1; C092069:activity regulated cytoskeletal-associated protein