Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: Reversal by tianeptine

Abstract

Excitatory amino acids play a key role in stress-induced remodeling of dendrites in the hippocampus as well as in suppression of neurogenesis in the dentate gyrus. The regulation of extracellular glutamate levels has been suggested as a potential mechanism through which repeated stress causes dendritic remodeling of CA3 pyramidal neurons. Accordingly, the current study examined the distribution and regulation of the glia glutamate transporter GLT-1 and the recently identified GLT isoform, GLT-1b, in the hippocampus of rats subjected to chronic restraint stress (CRS). We also examined the ability of the antidepressant tianeptine, which blocks CRS-induced dendritic remodeling, to modulate CRS-mediated changes in GLT-1 and GLT-1b expression. CRS increased GLT-1 mRNA expression in the dentate gyrus and CA3 region of Ammon's horn, increases that were inhibited by tianeptine. CRS more selectively increased GLT-1 protein levels in the subregion where dendritic remodeling is most prominent, namely the CA3 region, increases that were also inhibited by tianeptine administration. In contrast, GLT-1b mRNA expression was not modulated in the hippocampus in any of these groups, but CRS increased GLT-1b protein levels in all hippocampal subfields examined, increases that were unaffected by tianeptine treatment. These results point to the importance of understanding the mechanism for the differential and subregional regulation of GLT-1 isoforms in neuronal and glial compartments in the hippocampus as a basis for understanding the effects of chronic stress on structural plasticity as well as the neuroprotective properties of agents such as tianeptine.

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

“…The deficit in ED set shifting seen in the present study after CUS is consistent with a recent report , published as the current work was in preparation, in which a similar deficit in attentional set shifting was seen following repeated restraint stress, a model proposed to induce some of the pathological changes underlying affective disorders (McEwen, 2003;Reagan et al, 2004). In addition to the cognitive deficit, Liston et al (2006) also reported that repeated restraint stress induced apical dendritic atrophy of prefrontal cortical pyramidal neurons, in replication of previous studies (Radley et al, 2004.…”

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

“…Specifically, chronic restraint stress was associated with an increase in GLT1 mRNA and protein levels in the CA3 region of the hippocampus that was reversible by administration of the antidepressant tianeptine. 83 In contrast, GLT1b was regulated only at the protein level in several hippocampal subfields and the effects were not altered by tianeptine. GLT1 expression is also regulated by glucocorticoids including corticosterone and the synthetic molecule dexamethasone.…”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…NLGN-1 has a key role in the functioning of excitatory synapses and NLGN-2 has a similar role at inhibitory synapses 202 . Alterations in the neural E/I balance 203,204 are believed to underlie social deficits in psychiatric disorders, and chronic stress was shown to lead to an increase in the E/I balance 205,206,207 in the hippocampus of rodents. Chronic stress reduces NLGN-2, but not NLGN-1, expression throughout the hippocampus in parallel with decreased sociability and increased aggression in rats 13 [ figure, part c].…”