Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin

Wang, Xuezhen; Zhang, Di; Lu, Xin‐Yun

doi:10.1038/mp.2014.75

Cited by 41 publications

(56 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our recent studies have shown that hippocampal Akt signaling is critical for the antidepressant-like effect of leptin in male mice (29). We therefore determined whether there is an estrous cycle stage-dependent difference in leptin-stimulated hippocampal Akt signaling.…”

Section: Effects Of Leptin On Hippocampal Akt Phosphorylation In Intamentioning

confidence: 95%

“…This dose of leptin was chosen because of its effectiveness in inducing antidepressant-like effects in intact male mice (19,23,29). The estrous cycle phase was identified based on vaginal lavage prior to the treatments.…”

Section: Experimental Design Experiments 1: Antidepressant-like Effectmentioning

confidence: 99%

“…We have previously shown that leptin produces antidepressant-like effects in intact male mice in the forced swim test and tail suspension test (19,23,29,30). To determine whether antidepressant-like response to leptin in male mice is dependent on the presence of gonadal hormones, we examined the behavioral effects of leptin in castrated mice 2 weeks after castration in comparison with intact male mice.…”

Section: Antidepressant-like Effects Of Leptin In Ovx Female Mice Vs mentioning

confidence: 99%

“…It circulates in the blood and crosses the bloodbrain barrier to exert its effects on the central nervous system. LepRb is selectively expressed in particular brain regions, including the limbic structures such as the hippocampus (19,28,29). Although six isoforms of leptin receptors have been identified, only the long isoform (LepRb) has a complete intracellular domain with signaling capability (25)(26)(27).…”

mentioning

confidence: 99%

“…LepRb is selectively expressed in particular brain regions, including the limbic structures such as the hippocampus (19,28,29). Third, the blockade of leptin signaling in the dentate gyrus reverses the antidepressant-like effects of leptin (29). First, direct infusion of leptin into the dentate gyrus of the hippocampus induces an antidepressant-like effect (20).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin

et al. 2015

View full text Add to dashboard Cite

Sex differences in the incidence of depression and antidepressant treatment responses are well documented. Depression is twice as common in women as in men. Recent studies indicate that low levels of leptin, an adipocyte-derived hormone, are associated with increased symptoms of depression in women. Leptin has been shown to produce antidepressant-like effects in male rodents. In the present study, we examined sex differences and estrous cycle variations in antidepressant-like responses to leptin. Leptin administration significantly reduced immobility, a putative measure of behavioral despair, in the forced swim test in intact female mice in the proestrus phase but not in the diestrus phase of the estrous cycle. Moreover, leptin administration stimulated Akt phosphorylation in the hippocampus of female mice in proestrus but not in diestrus, in correlation with its differential behavioral effects in these two phases of the cycle. Leptin-induced behavioral responses and stimulation of hippocampal Akt phosphorylation in female mice were abolished by ovariectomy. By contrast, the antidepressant-like effect of leptin in male mice was not affected by gonadectomy (castration). Pretreatment with 17β-estradiol restored sensitivity to the effects of leptin on behavior and hippocampal Akt phosphorylation in ovariectomized female mice. These results suggest leptin regulates depression-like behavior and hippocampal Akt signaling in a sex-specific and estrous cycle-dependent manner.

show abstract

Section: Effects Of Leptin On Hippocampal Akt Phosphorylation In Intamentioning

confidence: 95%

Section: Experimental Design Experiments 1: Antidepressant-like Effectmentioning

confidence: 99%

Section: Antidepressant-like Effects Of Leptin In Ovx Female Mice Vs mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin

et al. 2015

View full text Add to dashboard Cite

show abstract

The effects of fluoxetine on oligodendrocytes in the hippocampus of chronic unpredictable stress‐induced depressed model rats

Wang

Luo

Tang

et al. 2020

J of Comparative Neurology

View full text Add to dashboard Cite

Depression is a mental illness which is harmful seriously to the society. This study investigated the effects of fluoxetine on the CNPase+ oligodendrocytes in hippocampus of the depressed rats to explore the new target structure of antidepressants. Male Sprague–Dawley rats were used to build chronic unpredictable stress (CUS) depressed model of rats. Then, the depressed rats were divided into the CUS standard group and the CUS + fluoxetine (CUS/FLX) group. The CUS/FLX group was treated with fluoxetine at dose of 5 mg/(kg·d) from the fifth week to seventh week. After 7 weeks CUS intervention, the sucrose preference of the CUS standard group was significantly lower than that of the control group and the CUS/FLX group. The stereological results showed that the total number of the CNPase+ cells in the CA1, CA3, and DG subfield of the hippocampus in the CUS standard group were significantly decreased, when compared with the CNPase+ cells in the control group. However, the total number of the CNPase+ cells in the CA1 and CA3 subfield of the hippocampus in the CUS standard group was significantly decreased when it compared with CNPase+ cells in the CUS/FLX group. Therefore, fluoxetine might prevent the loss of CNPase+ oligodendrocytes in CA1 and CA3 subfields of hippocampus of the depressed rats. The oligodendrocytes in hippocampus may play an important role in the pathogenesis of depression. The current result might provide structural basis for the future studies that search for new antidepressant strategies.

show abstract

The liver X receptors agonist GW3965 attenuates depressive‐like behaviors and suppresses microglial activation and neuroinflammation in hippocampal subregions in a mouse depression model

Zhu

et al. 2022

J of Comparative Neurology

View full text Add to dashboard Cite

Liver X receptors (LXRs) have recently been reported to be novel and potential targets for the reversal of depressive-like behaviors, but the mechanism remains unclear. Hippocampal neuroinflammation and impairment of the normal structure and function of microglia are closely associated with depression. To investigate the effects of LXRs agonist (GW3965) on neuroinflammation and microglia in the hippocampal formation of mice with chronic unpredictable stress (CUS)-induced depression, depressive-like behaviors were evaluated by behavioral tests, hippocampal LXRs gene expression were evaluated by qRT-PCR, the protein expression levels of interleukin-1β, tumor necrosis factor-α, inducible nitric oxide synthase, nuclear factor kappa B, and cluster of differentiation 206 were estimated by western blotting, modern stereological methods were used to precisely quantify the total number of microglia in each hippocampal subregion, and immunofluorescence was used to detect the density of activated microglia and the morphology of microglia. We found that GW3965 alleviated the depressive-like behavior induced by CUS, reversed the decrease in hippocampal LXRα and LXRβ induced by CUS, increased the protein expression of pro-inflammatory factors, and decreased the protein expression of antiinflammatory factors induced by CUS. Moreover, CUS intervention significantly increased the number of microglia in the CA1 region, CA2/3 region, and dentate gyrus and the density of activated microglia in the CA2/3 region and dentate gyrus and significantly decreased the endpoints of microglial branches and process length of microglia in the dentate gyrus, while 4 weeks of injections with GW3965 reversed these changes. These findings suggest that regulating the number, activated state, and morphology of microglia in hippocampal subregions might be an important basis for the antidepressant effects of LXRs.

show abstract

Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin

Cited by 41 publications

References 78 publications

Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin

Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin

The effects of fluoxetine on oligodendrocytes in the hippocampus of chronic unpredictable stress‐induced depressed model rats

The liver X receptors agonist GW3965 attenuates depressive‐like behaviors and suppresses microglial activation and neuroinflammation in hippocampal subregions in a mouse depression model

Contact Info

Product

Resources

About