Hippocampal Subgranular Zone FosB Expression Is Critical for Neurogenesis and Learning

Manning, Claire; Eagle, Andrew L.; Kwiatkowski, Christine C.; Woodworth, Hillary L.; Potter, Emily; Ohnishi, Yoshinori N.; Leinninger, Gina M.; Robison, Alfred J.

doi:10.1016/j.neuroscience.2019.03.022

Cited by 20 publications

(15 citation statements)

References 59 publications

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“…This hypothesis, however, has been difficult to explore because of the lack of reagents to identify NtsR1 neurons to study their specific Nts-mediated signaling pathways. Recently established genetic models now permit site-specific modulation of NtsR1-expressing cells that may assist the field in defining the coupling of NtsR1 across different brain regions ( 1 , 98 , 124 , 125 ), and thus the mechanism by which Nts-NtsR1 signaling modulates physiology.…”

Section: Central Neurotensin Receptors and Weight Modulationmentioning

confidence: 99%

The Role of Central Neurotensin in Regulating Feeding and Body Weight

Ramirez‐Virella

Leinninger

2021

Endocrinology

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The small peptide Neurotensin (Nts) is implicated in myriad processes including analgesia, thermoregulation, reward, arousal, blood pressure and modulation of feeding and body weight. Alterations in Nts have recently been described in individuals with obesity or eating disorders, suggesting that disrupted Nts signaling may contribute to body weight disturbance. Curiously, Nts mediates seemingly opposing regulation of body weight via different tissues. Peripherally-acting Nts promotes fat absorption and weight gain, while central Nts signaling suppresses feeding and weight gain. Thus, because Nts is pleiotropic, a location-based approach must be used to understand its contributions to disordered body weight and whether the Nts system might be leveraged to improve metabolic health. Here we review the role of Nts signaling in the brain to understand the sites, receptors and mechanisms by which Nts can promote behaviors that modify body weight. New techniques permitting site-specific modulation of Nts and Nts receptor- expressing cells suggest that, even in the brain, not all Nts circuitry exerts the same function. Intriguingly, there may be dedicated brain regions and circuits via which Nts specifically suppresses feeding behavior and weight gain vs. other Nts-attributed physiology. Defining the central mechanisms by which Nts signaling modifies body weight may suggest strategies to correct disrupted energy balance, as needed to address overweight, obesity and eating disorders.

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Section: Central Neurotensin Receptors and Weight Modulationmentioning

confidence: 99%

The Role of Central Neurotensin in Regulating Feeding and Body Weight

Ramirez‐Virella

Leinninger

2021

Endocrinology

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“…Previous studies showed FosB-/- mice inhibited microglial activation and the production of pro-inflammatory cytokines to control neuropathic pain (14,15). The levels of FosB in the dorsal hippocampus play an important role in both learning and hippocampal neurogenesis (25). Only persistent heterotopic pain in mice led to elevated FosB expression in the amygdala and the central nucleus of the spinal cord, and FosB levels remained elevated in the basal lateral amygdala of mice, which resulted in significant pain relief and persistent behavioral effects (15).…”

Section: Discussionmentioning

confidence: 99%

Small RNA sequencing reveals microRNAs related to neuropathic pain in rats

Dai

Wang

Yuan

et al. 2019

Braz J Med Biol Res

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The present study aimed to identify microRNAs (miRNAs) that are involved in neuropathic pain and predict their corresponding roles in the pathogenesis and development process of neuropathic pain. The rat model of neuropathic pain caused by spared nerve injury (SNI) was established in Sprague-Dawley male rats, followed by small RNA sequencing of the L3–L6 dorsal root ganglion. Real-time PCR was performed to validate the differently expressed miRNAs. Functional verification was performed by intrathecally injecting the animals with miRNA agomir. A total of 72 differentially expressed miRNAs were identified in the SNI rats, including 33 upregulated and 39 downregulated miRNAs. The results of qPCR further verified the expression levels of rno-miR-6215 (P=0.015), rno-miR-1224 (P=0.030), rno-miR-1249 (P=0.038), and rno-miR-488-3p (P=0.048), which were all significantly downregulated in the SNI rats compared to the control ones. The majority of differentially expressed miRNAs were associated with phosphorylation, intracellular signal transduction, and cell death. Target prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggested that these differentially expressed miRNAs targeted genes that are related to axon guidance, focal adhesion, and Ras and Wnt signaling pathways. Moreover, miR-1224 agomir significantly alleviated SNI-induced neuropathic pain. The current findings provide new insights into the role of miRNAs in the pathogenesis of neuropathic pain.

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“…ΔFosB has a well-established role in NAc in mediating stress susceptibility 13 – 15 and regulates synaptic and intrinsic properties of NAc medium spiny neurons 16 . It is also necessary in dorsal hippocampus (dHPC) for learning 17 , and regulates the excitability of dHPC CA1 neurons 18 as well as hippocampal neurogenesis 19 , 20 . ΔFosB is induced throughout HPC by stress and antidepressant treatment 13 , 21 – 23 , and vHPC CA3 ΔFosB is critical for the prophylactic effects of ketamine on stress responses 23 .…”

Section: Introductionmentioning

confidence: 99%

Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance

et al. 2020

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Chronic stress is a key risk factor for mood disorders like depression, but the stress-induced changes in brain circuit function and gene expression underlying depression symptoms are not completely understood, hindering development of novel treatments. Because of its projections to brain regions regulating reward and anxiety, the ventral hippocampus is uniquely poised to translate the experience of stress into altered brain function and pathological mood, though the cellular and molecular mechanisms of this process are not fully understood. Here, we use a novel method of circuit-specific gene editing to show that the transcription factor ΔFosB drives projection-specific activity of ventral hippocampus glutamatergic neurons causing behaviorally diverse responses to stress. We establish molecular, cellular, and circuit-level mechanisms for depression- and anxiety-like behavior in response to stress and use circuit-specific gene expression profiling to uncover novel downstream targets as potential sites of therapeutic intervention in depression.

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Hippocampal Subgranular Zone FosB Expression Is Critical for Neurogenesis and Learning

Cited by 20 publications

References 59 publications

The Role of Central Neurotensin in Regulating Feeding and Body Weight

The Role of Central Neurotensin in Regulating Feeding and Body Weight

Small RNA sequencing reveals microRNAs related to neuropathic pain in rats

Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance

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