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Open research questions in Neurogenesis and neuroplasticity mechanisms

530 gap statements mined from Neurogenesis and neuroplasticity mechanisms papers in our 7.9M-paper local library, which holds 1,613 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The gap in the current understanding of opioid addiction is the lack of knowledge about the molecular mechanisms involved. The study aims to fill this gap by investigating the effects of alpha-pinene on hippocampal MAPKs levels during chronic morphine exposure and withdrawal.

    Alpha-pinene modulates hippocampal MAPKs/c-Fos pathways during morphine dependence and withdrawal in rats · 2026 · DOI

  • However, the molecular mechanisms underlying these alterations remain poorly understood.

    Neuronal expression of E2F4DN restores adult neurogenesis in homozygous 5xFAD mice via TrkB signaling · 2026 · DOI

  • Most of these prior descriptions of the DG vasculature have been qualitative, and other important aspects of vessel morphology, like vessel diameter, have not been previously reported to our knowledge.

    Classic and novel features of the dentate gyrus vascular niche quantified through 3D vessel reconstruction · 2026 · DOI

  • How SUM inputs regulate adult-born DG (abDG) neurons to support memory processing remains unclear.

    Select properties of supramammillary input to adult-born dentate gyrus neurons · 2026 · DOI

  • Impaired motor function is a prominent early manifestation of various NDDs, yet the mechanisms remain elusive.

    Arhgef1 Deletion Disrupts Early Cortical Neurogenesis via PAK1 Overactivation and Causes Motor Dysfunction in Adulthood · 2026 · DOI

  • Cyclin-dependent kinases, CDK4 and CDK6, are central regulators of the G₁/S transition, but their role in cellular stress responses during neurodevelopment remains unclear.

    CDK4 and CDK6 variants in patients with primary microcephaly lead to cell cycle defects and mitochondria-induced apoptosis · 2026 · DOI

  • Although mitochondrial dysfunction is a recognised feature, how RARS2 deficiency disrupts neural lineage development remains unclear.

    Single-cell transcriptomics identifies neural fate disruption and glial reprogramming caused by RARS2 deficiency · 2026 · DOI

  • The contribution of white matter to maintaining neural connectivity and cognitive function remains comparatively underexplored.

    Does the Exercise Delay Age‐Related Cognitive Impairment: Conversation Between White Matter, Myelin Sheath, and Oligodendrocyte During Exercise? · 2026 · DOI

  • Severe lysine deficiency was associated with impaired hippocampal neurogenesis, altered behavior, and gut microbiota composition, suggesting a potential gut-brain axis involvement, although causality remains to be established.

    Dietary lysine deficiency impairs hippocampal-related functions and neurogenesis in rats · 2026 · DOI

  • Lysine, an essential amino acid, modulates neuronal activity and synaptic function; however, the impact of dietary lysine deficiency on neurogenesis remains unclear.

    Dietary lysine deficiency impairs hippocampal-related functions and neurogenesis in rats · 2026 · DOI

  • The ventricular-subventricular zone (V-SVZ) is the largest neurogenic niche in the postnatal mammalian brain, but its organization and migratory dynamics remain poorly understood in gyrencephalic species.

    Cytoarchitecture of neurogenic niche and neuroblast clusters in the postnatal microminipig brain · 2026 · DOI

  • MicroRNAs (miRNAs) are critical post-transcriptional regulators in this process, yet the functions of many remain unknown.

    miR-151-5p regulates neural stem cell fate by targeting APH1A to modulate Notch signaling gradients · 2026 · DOI

  • Hypothalamic adult neurogenesis is implicated in energy homeostasis; however, the impact of physical exercise, particularly under high-fat diet (HFD) conditions, on this process remains unclear.

    Effects of voluntary exercise, diet, and selenium on hypothalamic adult neurogenesis · 2026 · DOI

  • The developmental origins of health and disease (DOHaD) hypothesis suggests that environmental exposures during development can induce long-term health effects, yet the cellular origin of such persistence remains unclear.

    Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms · 2026 · DOI

  • The transcriptomic differences in IPCs underlying their differential capacity across species remain elusive.

    Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development · 2026 · DOI

  • The peroxisomal fission machinery is shared with mitochondria, and although mitochondrial fission regulates neural cell fate decisions during human neurogenesis, it remains unclear whether peroxisomal fission independently influences human neural development.

    PEX11β controls early neural progenitor fate through regulation of peroxisomal fission and lipid metabolism · 2026 · DOI

  • Increasing evidence supports important roles of post-transcriptional regulation in brain development; however, the precise mechanism remains unclear.

    Post-transcriptional regulation maintains neurogenic potential of human neural progenitor cells · 2026 · DOI

  • Outer radial glia (oRG) are abundant in the human fetal cortex but rare in rodents, yet their molecular regulation remains poorly understood.

    HOPX regulates the development and lineage progression of human stem cell-derived outer radial glia-like cells · 2026 · DOI

  • Vestibular dysfunction is strongly linked to cognitive impairment and dementia risk, yet its underlying mechanisms remain unclear, hindering treatment development.

    Aerobic Exercise Promotes Hippocampal Neurogenesis and Ameliorates Cognitive Dysfunction Induced by Unilateral Labyrinthectomy · 2026 · DOI

  • Investigate the effects of APN treatment on other signaling pathways involved in morphine dependence and withdrawal. Examine the long-term effects of APN treatment on morphine dependence and withdrawal. Study the potential therapeutic applications of APN in the treatment of opioid use disorder.

    Alpha-pinene modulates hippocampal MAPKs/c-Fos pathways during morphine dependence and withdrawal in rats · 2026 · DOI

  • Investigate the effects of ATP6AP2 overexpression on other aspects of neuronal plasticity, - Examine the impact of ATP6AP2 overexpression on male mice, - Explore the potential therapeutic applications of ATP6AP2…

    Homozygous overexpression of ATP6AP2 in female mice and its impact on running-induced modulation of the adult hippocampus · 2026 · DOI

  • Investigate the effects of PA on other cell types, - Examine the therapeutic potential of PA for neurodegenerative diseases, - Study the mechanisms underlying the dose-dependent effects of PA…

    Dose‐Dependent Biphasic Effect of Palmitic Acid on Oligodendrocyte Function: Impacts on Viability, Differentiation, and Myelination · 2026 · DOI

  • A more extensive study of the expression patterns of OLIG2 and DBX2 in human - Cell lineage tracing studies in human to confirm the findings from mouse…

    Development of the early fetal human thalamus: from a protomap to emergent thalamic nuclei · 2025 · DOI

  • Future research on the affordance of physical activity, cognitive stimulation, and mindfulness through the built environment to promote hippocampal neurosustainability and mental health in humans.

    The BDNF-Interactive Model for Sustainable Hippocampal Neurogenesis in Humans: Synergistic Effects of Environmentally-Mediated Physical Activity, Cognitive Stimulation, and Mindfulness · 2024 · DOI

  • Small sample size (n = 7 per group), - Limited to female mice, - No mention of control for potential confounding…

    Homozygous overexpression of ATP6AP2 in female mice and its impact on running-induced modulation of the adult hippocampus · 2026 · DOI

Most-cited papers in Neurogenesis and neuroplasticity mechanisms

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Open questions raised by papers listed on this page include: (1) The gap in the current understanding of opioid addiction is the lack of knowledge about the molecular mechanisms involved (“Alpha-pinene modulates hippocampal MAPKs/c-Fos pathways during morphine…”, 2026); (2) The molecular mechanisms underlying these alterations remain poorly understood (“Neuronal expression of E2F4DN restores adult neurogenesis in homozygous 5xFAD…”, 2026); (3) How SUM inputs regulate adult-born DG (abDG) neurons to support memory processing remains unclear (“Select properties of supramammillary input to adult-born dentate gyrus neurons”, 2026); (4) Impaired motor function is a prominent early manifestation of various NDDs, yet the mechanisms remain elusive (“Arhgef1 Deletion Disrupts Early Cortical Neurogenesis via PAK1 Overactivation…”, 2026); (5) Cyclin-dependent kinases, CDK4 and CDK6, are central regulators of the G₁/S transition, but their role in cellular stress responses during neurodevelopment remains unclear (“CDK4 and CDK6 variants in patients with primary microcephaly lead to cell cycle…”, 2026). 530 gap statements have been mined from Neurogenesis and neuroplasticity mechanisms papers in our 7.9M-paper local library, which holds 1,613 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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