Neuroprotective efficacy of P7C3 compounds in primate hippocampus

Bauman, Melissa D.; Schumann, Cynthia M.; Carlson, Erin L.; Taylor, Sandra L.; Vázquez‐Rosa, Edwin; Cintrón-Pérez, Coral J.; Shin, Min-Kyoo; Williams, Noelle S.; Pieper, Andrew A.

doi:10.1038/s41398-018-0244-1

Transl Psychiatry

2018

DOI: 10.1038/s41398-018-0244-1

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Neuroprotective efficacy of P7C3 compounds in primate hippocampus

Melissa D. Bauman

¹

,

Cynthia M. Schumann

²

,

Erin L. Carlson

³

et al.

Abstract: There is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, a target-agnostic in vivo screen in mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. Subsequently, neuroprotective efficacy of P7C3 compounds in a broad spectrum of preclinical rodent models has also been observed.… Show more

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Cited by 46 publications

(28 citation statements)

References 94 publications

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“…Importantly, we observed that GAL, via GALR2, enhanced the cell proliferation induced by the NPYY1 agonist in the dentate gyrus of the ventral hippocampus. In agreement, the molecule P7C3, known to have neuroprotective activity, was shown to increase the neuronal cell proliferation associated with antidepressant effects in rodents and primates (Bauman et al, 2018;Walker et al, 2015). GALR2/NPYY1R heteroreceptor complexes significantly increase in density, as shown with PLA upon combined treatment with GAL and the NPYY1R agonist in the subgranular zone in the ventral hippocampus.…”

Section: Discussionmentioning

confidence: 59%

“…Importantly, we observed that GAL, via GALR2, enhanced the cell proliferation induced by the NPYY1 agonist in the dentate gyrus of the ventral hippocampus. In agreement, the molecule P7C3, known to have neuroprotective activity, was shown to increase the neuronal cell proliferation associated with antidepressant effects in rodents and primates (Bauman et al, 2018; Walker et al, 2015).…”

Section: Discussionmentioning

confidence: 75%

See 1 more Smart Citation

Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus

Borroto‐Escuela

¹

,

Pita-Rodríguez

²

,

Fores‐Pons

³

et al. 2020

Journal Cellular Physiology

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Importantly, we observed that GAL, via GALR2, enhanced the cell proliferation induced by the NPYY1 agonist in the dentate gyrus of the ventral hippocampus. In agreement, the molecule P7C3, known to have neuroprotective activity, was shown to increase the neuronal cell proliferation associated with antidepressant effects in rodents and primates (Bauman et al, 2018;Walker et al, 2015). GALR2/NPYY1R heteroreceptor complexes significantly increase in density, as shown with PLA upon combined treatment with GAL and the NPYY1R agonist in the subgranular zone in the ventral hippocampus.…”

Section: Discussionmentioning

confidence: 59%

“…Importantly, we observed that GAL, via GALR2, enhanced the cell proliferation induced by the NPYY1 agonist in the dentate gyrus of the ventral hippocampus. In agreement, the molecule P7C3, known to have neuroprotective activity, was shown to increase the neuronal cell proliferation associated with antidepressant effects in rodents and primates (Bauman et al, 2018; Walker et al, 2015).…”

Section: Discussionmentioning

confidence: 75%

Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus

Borroto‐Escuela

¹

,

Pita-Rodríguez

²

,

Fores‐Pons

³

et al. 2020

Journal Cellular Physiology

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…while Prevotellaceae was increased from undetectable to 2.68% by P7C3-A20 treatment. We noticed that two previous independent clinical investigations have showed that Akkermansia was associated with a healthier metabolic status in patients with obesity, insulin resistance, and intestinal inflammation (Anhe et al, 2015;Dao et al, 2016).…”

Section: Discussionmentioning

confidence: 79%

“…Besides, the Prevotellaceae tended to be more abundant in healthy subjects compared with NAFLD patients (Shen et al, 2017). As rhesus monkeys with daily oral P7C3-A20 or vehicle for ~38 weeks and found that the pro-neurogenic efficacy of P7C3-A20 was comparable to that of NSI-189, a pro-neurogenic drug currently in clinical trials for patients with major depression (Bauman et al, 2018).…”

Section: Discussionmentioning

confidence: 93%

P7C3‐A20 alleviates fatty liver by shaping gut microbiota and inducing FGF21/FGF1, via the AMP‐activated protein kinase/CREB regulated transcription coactivator 2 pathway

Xia

¹

,

Sun

²

,

Zhang

³

et al. 2020

British J Pharmacology

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Mice were then administered either vehicle (TBI-Veh, Sham-Veh) or P7C3-A20 (10 mg⋅kg −1 ⋅day −1 intraperitoneally [IP]; TBI-P7C3-A20) for 4 wk. P7C3-A20 is an aminopropyl carbazole that elevates cellular nicotinamide adenine dinucleotide, enhances survival of adult-born young hippocampal neurons, and has been shown to preserve mature neurons and improve cognition in various models of nervous system disease and injury ( 25 – 45 ). Immediately after treatment completion, cognitive function in the 15-mo-old animals was evaluated through Morris water maze (MWM) testing.…”

Section: Resultsmentioning

confidence: 99%

P7C3-A20 treatment one year after TBI in mice repairs the blood–brain barrier, arrests chronic neurodegeneration, and restores cognition

Vázquez‐Rosa

¹

,

Shin

²

,

Dhar

³

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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