Reduced Expression of GABA Transporter GAT3 in Helpless Rats, an Animal Model of Depression

Zink, Mathias; Vollmayr, Barbara; Gebicke‐Haerter, Peter J.; Henn, Fritz A.

doi:10.1007/s11064-009-9947-2

Cited by 28 publications

(22 citation statements)

References 73 publications

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“…In rats inbred for learned helplessness a decreased expression of GLT‐1 in the DG and CA1/CA3 areas of the hippocampus (Zink et al, ) and, in independent studies, lastingly reduced glutamate uptake (Almeida et al, ) have been observed. In parallel, lower expression levels for hippocampal GAT‐3 are evident in these animals (Zink et al, ). Overall, these studies suggest that exposure to various stressors can either decrease or increase hippocampal glutamate and GABA levels and this may occur even concordantly.…”

Section: Discussionmentioning

confidence: 93%

Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron–astrocyte interaction in the dentate gyrus

Albrecht

Ivens

Papageorgiou

et al. 2016

Glia

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Childhood trauma is a well-described risk factor for the development of stress-related psychopathology such as posttraumatic stress disorder or depression later in life. Childhood adversity can be modeled in rodents by juvenile stress (JS) protocols, resulting in impaired coping with stressful challenges in adulthood. In the current study, we investigated the long-lasting impact of JS on the expression of molecular factors for glutamate and γ-aminobutyric acid (GABA) uptake and turnover in sublayers of the dentate gyrus (DG) using laser microdissection and quantitative real-time polymerase chain reaction. We observed reduced mRNA expression levels after JS for factors mediating astrocytic glutamate and GABA uptake and degradation. These alterations were prominently observed in the dorsal but not ventral DG granule cell layer, indicating a lasting change in astrocytic GABA and glutamate metabolism that may affect dorsal DG network activity. Indeed, we observed increased inhibition and a lack of facilitation in response to paired-pulse stimulation at short interstimulus intervals in the dorsal DG after JS, while no alterations were evident in basal synaptic transmission or forms of long-term plasticity. The shift in paired-pulse response was mimicked by pharmacologically blocking the astrocytic GABA transporter GAT-3 in naïve animals. Accordingly, reduced expression levels of GAT-3 were confirmed at the protein level in the dorsal granule cell layer of rats stressed in juvenility. Together, these data demonstrate a lasting shift in the excitatory/inhibitory balance of dorsal DG network activity by JS that appears to be mediated by decreased GABA uptake into astrocytes.

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Section: Discussionmentioning

confidence: 93%

Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron–astrocyte interaction in the dentate gyrus

Albrecht

Ivens

Papageorgiou

et al. 2016

Glia

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“…GAT1 knockout mice show reduced anxiety and depressive behavior, but have increased nervousness and tremors (Chiu et al, 2005; Liu et al, 2007). Downregulation of GAT3 expression has been associated with learned helplessness, a model of depression (Zink et al, 2009). Both GAT1 and GAT3 have been indicated as potential targets for drug therapy in treatment of neurological and psychiatric disorders.…”

Section: 0 Discussionmentioning

confidence: 99%

Raphe serotonin neurons are not homogenous: Electrophysiological, morphological and neurochemical evidence

et al. 2011

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The median (MR) and dorsal raphe (DR) nuclei contain the majority of the 5-hydroxytryptamine (5-HT, serotonin) neurons that project to limbic forebrain regions, are important in regulating homeostatic functions and are implicated in the etiology and treatment of mood disorders and schizophrenia. The primary synaptic inputs within and to the raphe are glutamatergic and GABAergic. The DR is divided into three subfields, i.e., ventromedial (vmDR), lateral wings (lwDR) and dorsomedial (dmDR). Our previous work shows that cell characteristics of 5-HT neurons and the magnitude of the 5-HT1A and 5-HT1B receptor-mediated responses in the vmDR and MR are not the same. We extend these observations to examine the electrophysiological properties across all four raphe subfields in both 5-HT and non-5-HT neurons. The neurochemical topography of glutamatergic and GABAergic cell bodies and nerve terminals were identified using immunohistochemistry and the morphology of the 5-HT neurons was measured. Although 5-HT neurons possessed similar physiological properties, important differences existed between subfields. Non-5-HT neurons were indistinguishable from 5-HT neurons. GABA neurons were distributed throughout the raphe, usually in areas devoid of 5-HT neurons. Although GABAergic synaptic innervation was dense throughout the raphe (immunohistochemical analysis of the GABA transporters GAT1 and GAT3), their distributions differed. Glutamate neurons, as defined by vGlut3 antibodies, were intermixed and co-localized with 5-HT neurons within all raphe subfields. Finally, the dendritic arbor of the 5-HT neurons was distinct between subfields. Previous studies regard 5-HT neurons as a homogenous population. Our data support a model of the raphe as an area composed of functionally distinct subpopulations of 5-HT and non-5-HT neurons, in part delineated by subfield. Understanding the interaction of the cell properties of the neurons in concert with their morphology, local distribution of GABA and glutamate neurons and their synaptic input, reveals a more complicated and heterogeneous raphe. These results provide an important foundation for understanding how specific subfields modulate behavior and for defining which aspects of the circuitry are altered during the etiology of psychological disorders.

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“…The rationale for this model stems from Seligman ' s hypothesis that depression can be induced by uncontrollable stress in individuals with a predisposition (Overmier and Seligman 1967). CLH rats exhibit a behavioural phenotype as well as biochemical changes well comparable to human depression (Enkel et al 2010), including alterations in hippocampal glutamatergic and GABAergic systems (Sartorius et al 2007;Zink et al 2007Zink et al , 2009.…”

Section: Treatmentmentioning

confidence: 99%

Increase of hippocampal glutamate after electroconvulsive treatment: A quantitative proton MR spectroscopy study at 9.4 T in an animal model of depression

Biedermann

Weber‐Fahr

Zheng

et al. 2011

The World Journal of Biological Psychiatry

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Reduced Expression of GABA Transporter GAT3 in Helpless Rats, an Animal Model of Depression

Cited by 28 publications

References 73 publications

Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron–astrocyte interaction in the dentate gyrus

Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron–astrocyte interaction in the dentate gyrus

Raphe serotonin neurons are not homogenous: Electrophysiological, morphological and neurochemical evidence

Increase of hippocampal glutamate after electroconvulsive treatment: A quantitative proton MR spectroscopy study at 9.4 T in an animal model of depression

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