bims-adhine 2026-08-02 papers

Front Mol Neurosci. 2026 ;19 1868741

Mechanobiology of hippocampal neurogenesis: directing neural stem cell fate through physical cues.

Irem Akyel, Emad Moeendarbary, Graham K Sheridan.

Adult hippocampal neurogenesis (AHN), the generation of new neurons in the dentate gyrus of the hippocampus, is a dynamic and tightly regulated process essential for memory encoding, regulation of emotions, and cognitive flexibility. While the molecular and biochemical underpinnings of AHN have been studied extensively, recent advances have illuminated the pivotal role of mechanical forces in shaping neural stem cell (NSC) behavior. This perspective highlights the emerging field of hippocampal mechanobiology, examining how the physical properties of the neurogenic niche, such as extracellular matrix (ECM) stiffness and parenchymal viscoelasticity, act in concert with instructive biomechanical cues to govern NSC fate decisions. We explore the cellular machinery responsible for mechanosensing, including integrins, mechanosensitive ion channels, and cytoskeletal networks, and dissect the downstream signaling pathways, such as Rho GTPases and YAP/TAZ, that translate mechanical stimuli into transcriptional responses. We also review how physiological and pathological alterations in tissue mechanics influence neurogenesis and evaluate the therapeutic potential of biomaterials and pharmacological agents designed to modulate how cells interact with their mechanical microenvironment. By integrating mechanobiological principles into the study of AHN, we suggest new avenues for understanding brain plasticity and developing regenerative strategies for neurological disorders.

Keywords: Piezo1; dentate gyrus; extracellular matrix; hippocampus; neural stem cell; neurogenesis

DOI: https://doi.org/10.3389/fnmol.2026.1868741

bioRxiv. 2026 Jul 17. pii: 2026.07.15.738260. [Epub ahead of print]

Hilar mossy cells control structural and functional organization in the dentate gyrus.

Corwin R Butler, Connor R Squellati, Alyssa B Danis, Arielle Isakharov, Gary L Westbrook, Eric Schnell.

Hilar mossy cells in the dentate gyrus project widely throughout the hippocampus, broadly contributing to circuit function. Their loss in disease is associated with local functional and structural rearrangements, including retrograde granule cell axon sprouting, aberrant neurogenesis, and disinhibition. To examine how mossy cell loss contributes to these circuit rearrangements, we ablated or silenced hilar mossy cells using viral approaches in transgenic (Crlr-Cre) mice. Both mossy cell ablation and silencing dramatically altered dentate gyrus structure and function, as assessed using immunohistochemical, viral labeling, electrophysiology, and anatomical methods. Both manipulations accelerated the maturation of adult-born neurons, but did not alter neuroblast proliferation or cause granule cell axon sprouting. However, mossy cell ablation, but not silencing, caused collapse of the inner molecular layer accompanied by proximal translocation of middle molecular layer inputs. In both cases, granule cell activity measured by cFos labeling and seizure susceptibility were unchanged after mossy cell loss, indicating functional compensation for the altered network organization. Our results highlight how mossy cells influence dentate gyrus organization and adult neurogenesis but also demonstrate the resilience of the hippocampal circuit to structural or functional perturbations.

DOI: https://doi.org/10.64898/2026.07.15.738260

Prog Neuropsychopharmacol Biol Psychiatry. 2026 Jul 31. pii: S0278-5846(26)00269-1. [Epub ahead of print] 111871

Sex differences in the effects of oral antibiotics on the cellular and behavioral consequences of sub-chronic stress in mice.

Elise Miller, Thomas Bork, Corey McCall, Kristen Allen, Ciara Hoover, Colin Nemeth, Anne Eby, Hannah Borrelli, Vincent Vandiver, Lila Trollip, Katherine Laird, Olivia Bereza, Grace Bean, Gemma Krautzel, Benjamin Sachs.

Stress-related psychiatric disorders are increasingly common conditions that are notoriously difficult to treat. Identifying the factors that increase the risk of these conditions and defining the biological mechanisms through which they promote the development of these disorders could inform disease pathophysiology and reveal novel therapeutic strategies to improve mental health. Clinical findings suggest that oral antibiotics increase the risk of depression and anxiety, but preclinical studies have had mixed results. Administering antibiotics to rodents has been reported to induce depression- or anxiety-like behavior in some studies but to protect against stress-induced increases in depression- and anxiety-like behavior in others. The reasons for these discrepancies are unclear. The current study examined the effects of antibiotics on stress susceptibility in a model of sub-chronic stress in male and female c57BL/6 mice. Following exposure to oral antibiotics and/or stress, mice were tested in a panel of behavioral assays prior to their brains being examined for potential changes in hippocampal neurogenesis and microglial number. Overall, our results indicate that antibiotics increased susceptibility to stress in several assays, and some of these effects were more pronounced in females than males. Exposure to antibiotics also reduced the proliferation of progenitor cells in the hippocampus of unstressed, but not stressed, animals of both sexes but did not significantly impact the number of microglia or immature neurons in the hippocampus. Future work should examine additional potential mechanisms through which antibiotics impact stress susceptibility and behavior in males and females.

Keywords: Anxiety; Dysbiosis; Gut-brain axis; Neurogenesis; Stress

DOI: https://doi.org/10.1016/j.pnpbp.2026.111871

Sci Rep. 2026 07 25. pii: 23224. [Epub ahead of print]16(1):

Vitamin a modulates neurogenesis-associated pathways and cholinergic signaling in Alzheimer's disease: potential role of reactive astrocytes via NGN2/SOX-11 and SIRT-1.

Nesrine Saeid El-Mezayen, Yara Alaa Eesa, Wed Alaa Hassan, Dina Ahmed Aly, Yassmen Soliman Saafan, Eman Mahmod Khedr, Aliaa Sherief, Eman Ali Elkordy.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder lacking effective disease-modifying therapies. A promising regenerative approach involves enhancing endogenous neurogenic capacity within the injured brain. Reactive astrocytes-stellate-like cells in the AD brain-may contribute to a pro-neurogenic environment through transcription factors (TFs) such as neurogenin 2 (NGN2) and SOX-11. This process is tightly regulated by epigenetic mechanisms, particularly SIRT-1, a neuroprotective histone deacetylase that modulates TF activity and neuronal fate. Vitamin A (VA), a key regulator of differentiation and epigenetic remodeling via its active metabolite retinoic acid, is stored in astrocytes and hepatic stellate cells (HSCs). We hypothesized that AD-related astrocyte activation depletes cerebral VA, mobilizes hepatic stores, contributes to liver fibrosis, and that VA supplementation may restore astrocytic function, activate endogenous TFs via SIRT-1, and drive cholinergic neuron regeneration. In a scopolamine (SCO)-induced AD rat model, VA biodistribution was traced using confocal microscopy. Brain and liver VA deficiency were confirmed via retinol-binding protein (RBP) and ALDH1A1 expressions. Rats received VA (1500, 3000, or 4500 IU/kg/day) or donepezil. Outcomes included neurogenesis (DCX), NGN2/SOX-11 expression, SIRT-1 activation, cholinergic regeneration, amyloid-β deposition, and serum tau. Liver fibrosis was assessed via TGF-β, hydroxyproline and histopathologically. AD induced systemic VA depletion and liver fibrosis. Medium-dose VA (VAMD) significantly enhanced neurogenesis, TF expression, SIRT-1 activation, cholinergic regeneration, and reversed liver fibrosis. VAMD demonstrated neuroregenerative and antifibrotic effects, indicating a possible therapeutic role in AD.

Keywords: Alzheimer’s disease; Astrocytes; NGN2; Neurogenesis; SIRT-1; SOX-11; Vitamin A

DOI: https://doi.org/10.1038/s41598-026-55386-z