The antidepressant effects of ventromedial prefrontal cortex stimulation is associated with neural activation in the medial part of the subthalamic nucleus

Lim, Lee Wei; Janssen, Mark; Kocabıcak, Ersoy; Temel, Yasin

doi:10.1016/j.bbr.2014.11.008

Cited by 28 publications

(24 citation statements)

References 24 publications

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“…In this rodent model for stress-related disorders, a drastic dendritic reorganization of pyramidal neurons was also reported in the medial PFC (Wellman 2001). Furthermore, in rats expressing a depressive-like behavior, cell activity measured by c-Fos immunoreactivity was decreased in the ventromedial PFC (Lim et al 2015). These data were supported by a study showing a decrease in both the excitatory and inhibitory neuronal functions in the PFC and a disturbed neurotransmitter homeostasis in the social defeat mouse model of depression (Veeraiah et al 2014).…”

Section: Brain Regions and Neurocircuits Involved In Depression: Neurmentioning

confidence: 99%

“…An 8-week escitalopram treatment was shown to reduce irregular high functional connectivity in the bilateral dorsal medial PFC in MDD patients (Lyttle et al 2015; Wang et al 2015a) and, in rats, a 2-week administration of a selective serotonin reuptake inhibitor (SSRI), fluvoxamine, restored dendritic length and spine densities but not cortical thickness after early-life stress exposure (Lyttle et al 2015). Furthermore, it appeared that both high- and low-frequency electrical ventromedial PFC stimulations in rat models of depression attenuated depressive-like behavior (Bruchim-Samuel et al 2016; Lim et al 2015). …”

Section: Brain Regions and Neurocircuits Involved In Depression: Neurmentioning

confidence: 99%

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Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

et al. 2018

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Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial effects by enhancing trophic signaling on neuronal and synaptic plasticity. However, current antidepressants still show a delayed onset of action, as well as lack of efficacy. Hence, a deeper understanding of the molecular and cellular mechanisms involved in the pathophysiology of depression, as well as in the action of antidepressants, might provide further insight to drive the development of novel fast-acting and more effective therapies. Here, we summarize the current literature on the involvement of neurotrophic factors in the pathophysiology and treatment of depression. Further, we advocate that future development of antidepressants should be based on the neurotrophin theory.

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Section: Brain Regions and Neurocircuits Involved In Depression: Neurmentioning

confidence: 99%

Section: Brain Regions and Neurocircuits Involved In Depression: Neurmentioning

confidence: 99%

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

et al. 2018

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“…Indication: *, significant difference from the sham rats, (p < 0.05). DOI: 10.7554/eLife.04803.008 studies of vmPFC HFS produced robust antidepressant-like behaviors (Lim et al, 2015a(Lim et al, , 2015b, we therefore applied this stimulation parameter in the chronic stimulation experiment to test the hypothesis that it would restore the memory deficits for both the short-and long-term memory functions of the middle-aged rats.…”

Section: Discussionmentioning

confidence: 99%

“…Surgery was performed as previously described (Lim et al, 2010(Lim et al, , 2015a. In brief, rats were anesthetized (2.5% isoflurane inhalation) and placed in a stereotactic frame (Vernier Stereotaxic Instrument, Leica Biosystems, Nussloch, Germany).…”

Section: Deep Brain Stimulationmentioning

confidence: 99%

Author response: Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

Liu

Jain

Vyas

et al. 2015

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Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short-and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders.

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“…The cylinder was filled with tap water (25 ± 1 °C) to a depth of 10 cm. The testing procedure was performed over two consecutive days as previously described5156. In a pre-test session, each mouse was placed in the water for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice

Lim

Shrestha

et al. 2016

Sci Rep

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Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A−/−) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A−/− mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A−/− mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A+/+ mice. This difference was abolished after ovariectomy, and administration of 17-β-estradiol benzoate (EB) restored this escalated anxiety-like behavior in TTC9A−/− mice. Since serotonin is well-known to be the key neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and serotonin transporter (5-HTT) were measured in the ventromedial prefrontal cortex (vmPFC) and dorsal raphe nucleus (DRN). Interestingly, the heightened anxiety in TTC9A−/− mice under EB influence is consistent with a greater induction of TPH 2, and 5-HTT by EB in DRN that play key roles in emotion regulation. In conclusion, our data indicate that TTC9A modulates the anxiety-related behaviors through modulation of estrogen action on the serotonergic system in the DRN.

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The antidepressant effects of ventromedial prefrontal cortex stimulation is associated with neural activation in the medial part of the subthalamic nucleus

Cited by 28 publications

References 24 publications

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

Author response: Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice

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