bims-adhine 2026-07-12 papers

Front Sports Act Living. 2026 ;8 1770350

Exercise training promotes neurogenesis in the adult hippocampus with a particular focus on cell cycle regulation.

Xiao-Tao Wang, Jia Wang, Xiao-Jiao Zhao.

Adult neurogenesis is predominantly restricted to two neurogenic regions in the mammalian brain: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG) within the hippocampus. The hippocampus serves as a critical brain structure involved in learning and memory processes, and the continuous generation of new neurons contributes to enhanced synaptic plasticity. Accumulating evidence has demonstrated that impaired hippocampal neurogenesis is closely associated with various neuropsychiatric disorders, including Alzheimer's disease, epilepsy, and traumatic brain injury. Although the precise molecular and cellular mechanisms underlying adult neurogenesis remain incompletely elucidated, extensive research over the past several decades has identified numerous endogenous, exogenous, and environmental factors that modulate this process. Notably, exercise training, as a key exogenous stimulus, has been shown to promote adult hippocampal neurogenesis by influencing the neurochemical environment and functional integration of newly generated neurons. This review aims to summarize the relationship between cell cycle dynamics and adult hippocampal neurogenesis, with a particular emphasis on how physical exercise regulates the cell cycle to activate and promote the proliferation of neural stem cells (NSCs) in the DG, thereby facilitating the differentiation and lineage progression of neural progenitor cells. A deeper understanding of the regulatory mechanisms by which exercise enhances adult hippocampal neurogenesis may provide novel insights into the development of therapeutic strategies for neurological and psychiatric disorders.

Keywords: cell cycle; exercise; hippocampus; neural stem cells; neurogenesis; self-renewal

DOI: https://doi.org/10.3389/fspor.2026.1770350

Nat Commun. 2026 Jul 07. pii: 5287. [Epub ahead of print]17(1):

TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells.

Tinne A D Nissen, Arishma Baig, Sahand Farmand, Daniel T Rock, Sandra Shibu, Hyunah Lee, Lauren A O'Neill, Vikki Houghton, Susan John, Linda S Klavinskis, Sandrine Thuret.

Adult hippocampal neurogenesis is essential for learning, memory, and mood regulation, and its disruption is implicated in ageing, neurodegeneration, and mood disorders. However, the mechanisms linking inflammation to adult hippocampal neurogenesis impairment remain unclear. Here, we identify chronic tumour necrosis factor-alpha signalling as a key driver of neurogenic dysregulation via a previously unrecognised type I interferon autocrine/paracrine loop in human hippocampal progenitor cells. Using a female-derived human in vitro neurogenesis model, single-cell RNA sequencing, and functional T cell migration assays, we show that tumour necrosis factor-alpha induces a robust type I interferon response in hippocampal progenitor cells, promoting chemokine-mediated and CXC motif chemokine receptor 3-dependent T cell recruitment and suppressing neurogenesis. This inflammatory signalling cascade drives a fate switch in hippocampal progenitor cells from a neurogenic trajectory towards an immune-defensive phenotype, with critical implications for infectious and inflammatory disease pathogenesis. These findings uncover a key inflammatory checkpoint regulating human adult hippocampal neurogenesis and highlight potential therapeutic targets to restore neurogenesis in chronic inflammatory states.

DOI: https://doi.org/10.1038/s41467-026-74104-x

ACS Chem Neurosci. 2026 Jul 08.

Serotonin Deficits Modulate Hippocampal Plasticity.

Rocío B Foltran, Mariano Soiza-Reilly.

Serotonin (5-HT) modulates a wide variety of functions across the central nervous systems. It is a key regulator of neuroplasticity, particularly in the hippocampus, where increased serotonergic signaling generally enhances the plasticity processes. However, the consequences of 5-HT deficiency on brain plasticity remain poorly understood, which is essential for clarifying the role of 5-HT in the etiology and treatment of psychiatric disorders. Here, we survey findings from pharmacological and genetic models of 5-HT depletion, focusing on molecular, cellular, and neural circuit changes in the hippocampus, alongside related phenotypes. Evidence indicates that lowering 5-HT levels differentially impacts the distinct forms of plasticity. While chronic depletion frequently increases molecular plasticity markers, dendritic spines, and neurogenesis, it simultaneously impairs neural circuit plasticity and hippocampus-dependent memory. In contrast, both acute and developmental 5-HT depletion consistently reduce both the structural and functional neuronal plasticity of the hippocampus. These findings highlight that the effects of 5-HT deficiency are highly dependent on the timing, duration, and developmental stages of the manipulation. Deconstructing this complexity is critical to interpreting how reduced 5-HT levels alter hippocampal plasticity and contribute to psychiatric pathophysiology.

Keywords: BDNF; adult neurogenesis; learning and memory; morphology; physiology; serotonin depletion

DOI: https://doi.org/10.1021/acschemneuro.6c00120

Adv Sci (Weinh). 2026 Jul 09. e76479

RPLP2 Mediates the Beneficial Effects of Exercise on Stress Resistance Through Muscle-Brain Communication.

Peiyu Luo, Wei Wu, Huan Peng, Dan He, Yuxi Guo, Boyue Zhao, Xiaodan Wang, Li Ma, Yuhang Qin, Yifang Zhai, Lixia Zhuo, Ying Zhang, Yijie Guo, Linlin Jing, Fangyao Chen, Erfei Zhang, Wei Wang, Xiancang Ma, Yan Li.

Anxiety disorders pose a considerable burden on public health. While exercise has been increasingly established as a viable strategy for preventing and alleviating anxiety symptoms, the underlying molecular mechanisms of this action remain elusive. We previously conducted an 8-week randomized controlled trial which suggested that exercise not only significantly reduced anxiety levels but also triggered the release of acidic ribosomal protein P2 (RPLP2) from peripheral tissues into the bloodstream. These elevated circulating RPLP2 levels showed an inverse association with anxiety severity in patients, suggesting a potential therapeutic role for the protein. Further experiments in mice confirmed that skeletal muscle-derived RPLP2 exerts its anxiolytic effects by facilitating hippocampal neurogenesis. Mechanistically, RPLP2 facilitates ribosomal localization and increases the efficiency of ribosomal subunit assembly, thereby increasing local protein synthesis and supporting the development and maturation of newly generated neurons. The successful maturation of these neurons, in turn, promotes morphological and functional synaptic plasticity, which is crucial for the integration and functional maturation of newborn neurons into hippocampal circuits. Collectively, our findings reveal a previously unknown muscle-brain axis mediated by RPLP2, offering mechanistic evidence for exercise-induced stress resistance.

Keywords: RPLP2; anxiety disorders; exercise; muscle–brain communication; neurogenesis; ribosome assembly; stress resistance

DOI: https://doi.org/10.1002/advs.76479

Front Physiol. 2026 ;17 1772055

What role does the Notch signaling pathway play in exercise-related metabolic and neurological adaptations? A molecular-to-systems perspective.

Lin Li, Jianda Kong, Xuewen Tian.

The Notch signaling pathway is a highly conserved cell-cell communication system that plays central roles in stem-cell maintenance, tissue homeostasis, cell-fate determination, and metabolic regulation. Because exercise induces coordinated adaptations across the nervous, muscular, cardiovascular, and metabolic systems, Notch signaling has emerged as a potential mediator of exercise-associated plasticity. However, whether exercise directly activates or suppresses Notch signaling in a causal, tissue-specific, and intensity-dependent manner remains unresolved. In this narrative review, we synthesize evidence on canonical and non-canonical Notch signaling, its functions in neural and metabolic regulation, and its potential intersections with exercise-related neurogenesis, muscle remodeling, redox balance, and metabolite signaling. We contend that the current evidence is best understood within a context-dependent framework rather than through a universal model of exercise-induced Notch activation. In particular, categories such as "moderate" and "high-intensity" exercise should be interpreted as individualized physiological domains defined relative to markers including lactate and ventilatory thresholds, cardiorespiratory reserve, and baseline fitness. We further propose that exercise-derived metabolites, including lactate, ketone bodies, and shifts in cellular NAD+/AMP status, may modulate Notch-related signaling indirectly or in a cell-type-specific manner; however, these interactions should currently be regarded as hypothesis-generating rather than established linear pathways. Across tissues, the strongest mechanistic evidence pertains to Notch biology in neural stem cells, synaptic plasticity-associated signaling, and skeletal-muscle stem-cell regulation, whereas direct human exercise studies assessing Notch pathway activation remain scarce. We therefore propose a context-dependent working model in which Notch acts as a potential integrator of exercise-responsive neural and metabolic cues, while also emphasizing major limitations, conflicting findings, and the safety concerns associated with systemic pharmacological modulation of this pathway. Overall, this perspective positions Notch signaling as a plausible, though not yet universally validated, component of exercise-associated adaptation and a priority target for future mechanistic investigation.

Keywords: Notch signaling; exercise; metabolic homeostasis; neurogenesis; neuroplasticity; oxidative stress

DOI: https://doi.org/10.3389/fphys.2026.1772055