TrkB Signaling Influences Gene Expression in Cortistatin-Expressing Interneurons

Maynard, Kristen R.; Kardian, Alisha; Hill, Joanne M.; Mai, Yishan; Barry, Brianna K.; Hallock, Henry L.; Jaffe, Andrew E.

doi:10.1523/eneuro.0310-19.2019

Cited by 13 publications

(7 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1c, Extended Data Fig. 1b, c, Extended Data Table 1), similar to previous studies in other types of neurons 30,31 .…”

Section: Transcriptome Landscape Of the Drn Serotonin Neuronssupporting

confidence: 89%

Transcriptional landscape of the dorsal raphe serotonin neurons rendering stress resiliency

Andoh,

Otani,

Noguchi

et al. 2024

Preprint

View full text Add to dashboard Cite

Major depressive disorder (MDD) is a serious and large social problem, yet the pathophysiology of MDD and the action mechanism of antidepressants are still poorly understood. A number of studies have reported that activation and inactivation of serotonin neurons in the dorsal raphe nucleus (DRN) cause antidepressant-like effects and depressive-like behaviors, respectively. Also, their physiological neural activities are increased when mice were chronically administered an SSRI and decreased in mice exposed to chronic social defeat stress (CSDS), a mouse model of depression. However, the molecular mechanism underlying these neural activity changes in DRN serotonin neurons remains unclear. In this study, we performed a DRN serotonin neuron-specific comprehensive gene expression analysis by using Translating Ribosome Affinity Purification (TRAP) technology in both chronic SSRI-treated mice as a model of antidepressant treatment and CSDS mice as a model of depression. It revealed that many gene expression changes were the opposite between SSRI-treated mice and CSDS-susceptible mice. Among these, we identified S100a10 as a prodepressive gene in DRN serotonin neurons, and we found that Interleukin-4 (IL-4) – Signal Transducer and Activator of Transcription 6 (STAT6) pathway and 5-HT1Breceptor were the upstream and downstream molecules of S100a10, respectively. Our findings provide insights into molecular mechanisms underlying the action of antidepressants and stress resiliency.

show abstract

“…1c, Extended Data Fig. 1b, c, Extended Data Table 1), similar to previous studies in other types of neurons 30,31 .…”

Section: Transcriptome Landscape Of the Drn Serotonin Neuronssupporting

confidence: 89%

Transcriptional landscape of the dorsal raphe serotonin neurons rendering stress resiliency

Andoh,

Otani,

Noguchi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…27 Given that lower BDNF has also been reported in MDD, 27,49,50 altered BDNF signaling might account for lower neuropeptide levels in the superficial zone in MDD. 51 CORTexpressing neurons also depend on BDNF signaling, 52 and CORT levels have been reported to be lower in DLPFC total gray matter 25,27 and other frontal regions 49 in MDD. However, we did not find differences in CORT expression in any group, which might reflect differences in sequence targeting or laminar zones studied.…”

Section: Molecular Alterations In Sst Neurons In Both Superficial And...mentioning

confidence: 99%

Diagnostic Specificity and Association With Cognition of Molecular Alterations in Prefrontal Somatostatin Neurons in Schizophrenia

Dienel,

Dowling,

Barile

et al. 2023

JAMA Psychiatry

View full text Add to dashboard Cite

ImportanceIndividuals with schizophrenia (SZ) exhibit pronounced deficits in somatostatin (SST) messenger RNA (mRNA) levels in the dorsolateral prefrontal cortex (DLPFC). Molecularly distinct subtypes of SST neurons, located in the superficial and deep zones of the DLPFC, are thought to contribute to different functional processes of this region; understanding the specificity of SST alterations in SZ across these zones could inform the functional consequences of those alterations, including cognitive impairments characteristic of SZ.ObjectiveTo quantify mRNA levels of SST and related neuropeptides in the DLPFC in individuals with SZ, bipolar disorder (BPD), or major depressive disorder (MDD) and unaffected comparison individuals.Design, Setting, and ParticipantsThis case-control study, conducted from January 20, 2020, to March 30, 2022, used postmortem brain tissue specimens previously obtained from individuals with SZ, MDD, or BPD and unaffected individuals from a community population through 2 medical examiners’ offices. Demographic, clinical, and educational information was ascertained through psychological autopsies.ExposuresDiagnosis of SZ, BPD, or MDD.Main Outcome and MeasuresThe main outcome was levels of SST and related neuropeptide mRNA in 2 DLPFC zones, examined using laser microdissection and quantitative polymerase chain reaction or fluorescent in situ hybridization (FISH). Findings were compared using educational attainment as a proxy measure of premorbid cognition.ResultsA total of 200 postmortem brain specimens were studied, including 65 from unaffected comparison individuals (42 [65%] male; mean [SD] age, 49.2 [14.1] years); 54 from individuals with SZ (37 [69%] male; mean [SD] age, 47.5 [13.3] years); 42 from individuals with MDD (24 [57%] male; mean [SD] age, 45.6 [12.1] years); and 39 from individuals with BPD (23 [59%] male; mean (SD) age, 46.2 [12.5] years). Compared with unaffected individuals, levels of SST mRNA were lower in both superficial (Cohen d, 0.68; 95% CI, 0.23-1.13; P = .004) and deep (Cohen d, 0.60; 95% CI, 0.16-1.04; P = .02) DLPFC zones in individuals with SZ; findings were confirmed using FISH. Levels of SST were lower only in the superficial zone in the group with MDD (Cohen d, 0.58; 95% CI, 0.14-1.02; P = .12), but the difference was not significant; SST levels were not lower in either zone in the BPD group. Levels of neuropeptide Y and tachykinin 1 showed similar patterns. Neuropeptide alterations in the superficial, but not deep, zone were associated with lower educational attainment only in the group with SZ (superficial: adjusted odds ratio, 1.71 [95% CI, 1.11-2.69]; P = .02; deep: adjusted odds ratio, 1.08 [95% CI, 0.64-1.84]; P = .77).Conclusions and RelevanceThe findings revealed diagnosis-specific patterns of molecular alterations in SST neurons in the DLPFC, suggesting that distinct disease processes are reflected in the differential vulnerability of SST neurons in individuals with SZ, MDD, and BPD. In SZ, alterations specifically in the superficial zone may be associated with cognitive dysfunction.

show abstract

“…It is hypothesized that BDNF may inhibit epilepsy by promoting phosphorylation of certain subunits of GABAergic neurons to attenuate the disease-induced decrease in GABAergic neuronal excitability (Cifelli et al, 2013). In a recent study, loss of BDNF-TrkB signaling in the cortistatin-expressing interneurons resulted in behavioral hyperactivity and SRS in mice (Maynard et al, 2020). Meanwhile, BDNF could alleviate the inflammatory response associated with epileptogenesis and thus reduce the disruption of the blood-brain barrier, as well as reduce the number of SRS in an epilepsy model of rats (Bovolenta et al, 2010).…”

Section: Evidences From Preclinical Trialsmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update

Wang

2021

Front. Pharmacol.

View full text Add to dashboard Cite

Epilepsy, which is characterized by spontaneous recurrent seizures, is one of the most common and serious chronic neurological diseases in the world. 30% patients failed to control seizures with multiple anti-seizure epileptic drugs, leading to serious outcomes. The pathogenesis of epilepsy is very complex and remains unclear. Brain-derived neurotrophic factor (BDNF), as a member of the neurotrophic factor family, is considered to play an important role in the survival, growth and differentiation of neurons during the development of the central nervous system. Recent years, a series of studies have reported that BDNF can maintain the function of the nervous system and promotes the regeneration of neurons after injury, which is believed to be closely related to epileptogenesis. However, two controversial views (BDNF inhibits or promotes epileptogenesis) still exist. Thus, this mini-review focuses on updating the new evidence of the role of BDNF in epileptogenesis and discussing the possibility of BDNF as an underlying target for the treatment of epilepsy.

show abstract

TrkB Signaling Influences Gene Expression in Cortistatin-Expressing Interneurons

Cited by 13 publications

References 103 publications

Transcriptional landscape of the dorsal raphe serotonin neurons rendering stress resiliency

Transcriptional landscape of the dorsal raphe serotonin neurons rendering stress resiliency

Diagnostic Specificity and Association With Cognition of Molecular Alterations in Prefrontal Somatostatin Neurons in Schizophrenia

The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update

Contact Info

Product

Resources

About