ArticleBiological psychiatry global open science2025
Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice.
Article in Biological psychiatry global open science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- DKK2 contributes to context discrimination and adult hippocampal neurogenesis by suppressing Wnt/PCP signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Reduced Adult Neurogenesis in Humans Results From a Tradeoff Rather Than Direct Negative Selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Sex-specific behavioral changes in middle-aged mice.Scientific reports · 2025Article
- Modulation of adult hippocampal neurogenesis by interleukin 1 signaling.Neurobiology of sleep and circadian rhythms · 2025Article
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17 authors.
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Abstract
Background: Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, and age-related cognitive decline. Although BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested. Methods: In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis. One compound with a favorable profile, RO6871135, was then tested in young and aged mice for effects on BPS and anxiety-related behaviors. Results: Chronic treatment with RO6871135 (7.5 mg/kg) increased adult hippocampal neurogenesis and improved BPS in a fear discrimination task in both young and aged mice. RO6871135 treatment also lowered innate anxiety-like behavior, which was more apparent in mice exposed to chronic corticosterone. Ablation of adult hippocampal neurogenesis by hippocampal irradiation supported a neurogenesis-dependent mechanism for RO6871135-induced improvements in BPS. To identify possible mechanisms of action, in vitro and in vivo kinase inhibition and chemical proteomics assays were performed. These tests indicated that RO6871135 inhibited CDK8, CDK11, CaMKIIa, CaMKIIb, MAP2K6, and GSK-3β. An analog compound also demonstrated high affinity for CDK8, CaMKIIa, and GSK-3β. Conclusions: These studies demonstrate a method for empirical identification and preclinical testing of novel neurogenic compounds that can improve BPS and point to possible novel mechanisms that can be interrogated for the development of new therapies to improve specific endophenotypes such as impaired BPS.
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