bims-blobar 2025-08-24 papers

Issue of 2025–08–24
three papers selected by
Nicolas Rebergue

Neurochem Res. 2025 Aug 18. 50(5): 269

Progressive Blood-Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk.

Jessica J Avilez-Avilez, Jesús Enrique García-Aviles, Ricardo Jair Ramírez-Carreto, Verónica Salas-Venegas, Mara A Guzmán-Ruiz, Fernanda Medina-Flores, Mina Königsberg, Anahí Chavarría, Beatriz Gómez-González.

Sleep loss promotes a chronic low-grade inflammatory status with increased levels of inflammatory cytokines. Sleep loss also induces low-grade neuroinflammation characterized by glial reactivity and blood-brain barrier (BBB) dysfunction, as evidenced by BBB hyperpermeability and tight junction disassembly. Additionally, it raises molecules related to the senescence-associated secretory phenotype (SASP) in aged subjects, suggesting an increase in senescent cells. Here, we assessed the impact of sleep restriction on cellular senescence, neuroinflammation, and BBB function in the cerebral cortex and hippocampus of young male C57BL/6 mice. Sleep restriction induced a progressive increase in BBB permeability after 3, 5, and 10 days, along with a higher expression of the astroglial marker, the glial fibrillary acidic protein (GFAP), and the expression of the C3 complement component. The pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) increased in a region-dependent form. Furthermore, the progressive increase of the senescence markers β-galactosidase and p21 observed in both brain regions was accompanied by a neurotoxic astroglial response. Our data suggest that sleep restriction promotes cellular senescence in the cerebral cortex and hippocampus of young mice.

Keywords: Astrogliosis; Blood–brain barrier; Cellular senescence; Neuroinflammation; Sleep restriction

DOI: https://doi.org/10.1007/s11064-025-04510-y

Ageing Res Rev. 2025 Aug 15. pii: S1568-1637(25)00220-X. [Epub ahead of print]112 102874

Platelets: A new therapeutic target for neurological diseases.

Xin-Xin Wei, Xiao-Qing Tang.

Beyond their classical roles in hemostasis and coagulation, accumulating evidence highlights platelets as multifaceted regulators within the nervous system. Research has revealed that platelet-derived factors promote blood-brain barrier (BBB) maturation and angiogenesis via neurochemical pathways. At the same time, platelet-rich plasma (PRP) facilitates neural regeneration by mitigating the neurotoxicity of amyloid-beta (Aβ) and activating the PI3k/Akt signaling pathway. Platelets also modulate synaptic plasticity through NMDA receptor-dependent mechanisms and regulate the synthesis of neurotransmitters. Pathologically, platelets emerge as key contributors to neurodegeneration. They exacerbate Alzheimer's disease (AD) pathology by releasing Aβ and promoting tau hyperphosphorylation, trigger migraines via P2Y12-mediated platelet-leukocyte aggregates and serotonin dysregulation, and amplify neuroinflammation in multiple sclerosis (MS) through CD40L-dependent BBB disruption. Conversely, inhibiting platelet activation using PAFR antagonists (Ginkgolide B), P2Y12 inhibitors (Clopidogrel), or cyclooxygenase modulators (Aspirin) can alleviate neuroinflammation, reduce pathological protein accumulation, and promote functional recovery. This review summarizes the mechanistic roles of platelets in both nervous system physiology and neuropathology, proposing novel platelet-targeted preventive and therapeutic strategies.

Keywords: Inflammation; Nerve regeneration; Neurological diseases; Neurotransmitter; Platelet; Synaptic plasticity

DOI: https://doi.org/10.1016/j.arr.2025.102874

PeerJ. 2025 ;13 e19818

The role of T cells in the treatment of Parkinson's disease.

Zhuomiao Lin, Xihui Yu, Yunming Zhong, Guozhu Tan, Jiahong Zhong.

Current pharmacological treatment of Parkinson's disease (PD) predominantly employs dopaminergic agents aimed at enhancing cerebral dopamine levels. While these therapeutic strategies provide symptomatic relief, their palliative nature is frequently associated with dose-dependent complications, including gastrointestinal disturbances, emetic symptoms, and motor complications such as dyskinesia. Moreover, the honeymoon period of drugs has greatly limited their clinical application. The multifactorial etiology of PD continues to challenge researchers, yet substantial evidence implicates α-synuclein as a critical pathogenic mediator. Emerging findings suggest that dysregulated neuroimmune interactions constitute a fundamental mechanism in PD progression, where chronic immune activation appears particularly detrimental to neuronal survival. Notably, neuroinflammatory cascades coupled with compromised blood-brain barrier (BBB) integrity create a self-perpetuating cycle of neural degeneration, wherein α-synuclein-specific T cells exacerbate disease pathology while regulatory T cell populations demonstrate potential immunomodulatory capacities. This review systematically examines the mechanistic interplay involving neuroinflammatory cascades, BBB compromise, central nervous system (CNS) immunoregulation, and T lymphocyte subpopulations (including regulatory T cells) in the pathogenesis of PD. By synthesizing current evidence, we aim to establish a conceptual framework supporting the investigation of cellular immunity-based therapies for PD.

Keywords: Cellular immunity; Inflammation; Parkinson’s disease; Regulatory T cells; T cells

DOI: https://doi.org/10.7717/peerj.19818