Effects of Depressive-Like Behavior of Rats on Brain Glutamate Uptake

Abstract

Learned helplessness paradigm is a widely accepted animal model of depressive-like behavior based on stress. Glutamatergic system is closely involved with the stress-neurotoxicity in the brain and recently it is pointed to have a relevant role in the pathophysiology of depression disorder. Glutamate uptake is the main mechanism to terminate the glutamatergic physiological activity and to neuroprotection against excitotoxicity. We investigated the profile of glutamate uptake in female rats submitted to the learned helplessness paradigm and to different classes of stress related to the paradigm, in slices of brain cortex, striatum and hippocampus. Glutamate uptake in slices of hippocampus differ between learned helplessness (LH) and non-learned helplessness (NLH) animals immediately persisting up to 21 days after the paradigm. In addition, there were a decrease of glutamate uptake in the three brain structures analyzed at 21 days after the paradigm for LH animals. These results may contribute to better understand the role of the glutamatergic system on the depressive-like behavior.

Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behaviors through Reduced Secretion of FGF2

“…Indeed, such glutamate-related astrocytic and neuronal functions have consistently been implicated in both chronic stress models and MDD pathophysiology (Almeida et al, 2010; Bechtholt-Gompf et al, 2010; Hashimoto et al, 2007; Miguel-Hidalgo et al, 2010; Caudal et al, 2010); e.g., chronic stress induces a persistent potentiation of glutamate receptor membrane trafficking and glutamatergic transmission in the rat PFC (Yuen et al, 2012). Yet, little is known about whether glia plays any roles in the manifestation of such maladaptive outcomes.…”

“…The prominent behavioral disturbances and MDD-related glutamatergic deficits in neurons and astrocytes (Almeida et al, 2010; Bechtholt-Gompf et al, 2010; Caudal et al, 2010; Yuen et al, 2012) observed following NG2 glial ablation led us to question whether NG2 glia density is reduced during the emergence of depressive-like behaviors. Chronic stress is a primary predictor of various cognitive and emotional disturbances in neuropsychiatric disorders, such as MDD and post traumatic stress disorder (PTSD).…”

Astrocytes gate Hebbian synaptic plasticity in the striatum

“…The pharmacological blockade of EAAT2 with DHK impairs spatial memory and induces depression and anhedonia and ceftriaxone has been reported to display antidepressant effects46. EAAT2 downregulation in striatum is also found in a rat model of depression59. EAAT2 KO mice exhibit seizures and premature death69.…”

Disturbance of the glutamatergic system by glutaric acid in striatum and cerebral cortex of glutaryl-CoA dehydrogenase-deficient knockout mice: Possible implications for the neuropathology of glutaric acidemia type I

“…Slices (400 μm) were prepared from these cerebral structures using a McIlwain tissue chopper, washed with 1 mL Na + -free medium and placed into 24-well culture plates at 35°C. Glutamate uptake experiments were carried out in the presence of high sodium concentrations, which favors glutamate binding to high-affinity uptake carriers [26,27]. We used Hank's buffered salt solution (HBSS) containing (in mM) 137 NaCl, 0.63 Na 2 HPO 4 , 4.17 NaHCO 3 , 5.36 KCl, 0.44 KH 2 PO 4 , 1.26 CaCl 2 , 0.41 MgSO 4 , 0.49 MgCl 2 , and 5.5 glucose (pH 7.2) for measuring this uptake.…”