bims-adhine 2026-09-27 papers

Int J Biol Macromol. 2026 Sep 21. pii: S0141-8130(26)04503-4. [Epub ahead of print]383(Pt 1): 154555

New small isoform of glial cell line-derived neurotrophic factor djGDNF47 promotes neuronal viability, differentiation, and adult neurogenesis: Evidence from in vitro and in vivo models.

Olga Astakhova, Dzhirgala Shamadykova, Elena Rybnikova, Galina Pavlova.

Neurodegenerative diseases are characterized by progressive neuronal loss, and current therapies provide only symptomatic relief. Parkinson's disease (PD), a leading example, is marked by progressive dopaminergic neuron loss. Although glial cell line-derived neurotrophic factor (GDNF) supports dopaminergic neuron survival, its poor blood-brain barrier (BBB) permeability limits clinical application. Neuron-like SH-SY5Y and PC12 cell lines were used to assess metabolic and proliferative effects of djGDNF47 using MTS and 5-ethynyl-2'-deoxyuridine (EdU) assays, while neuroinductive properties were evaluated in PC12 cells and rat hippocampal neurons by measuring neurite length. Neuroprotective effects were examined in an MPP+-induced dopaminergic neurotoxicity model in SH-SY5Y cells by analyzing cell viability and apoptosis-related gene expression. In vivo, assess adult neurogenesis via 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry in the olfactory bulb and dentate gyrus. djGDNF47 induced concentration- and time-dependent metabolic effects, with early responses in both cell lines and sustained effects in PC12 cells at higher concentrations. Proliferation increased in SH-SY5Y cells but decreased in PC12 cells, consistent with djGDNF47-induced differentiation, accompanied by enhanced neurite outgrowth, which was confirmed by increased MAP2+ neurite length in hippocampal neurons. In the dopaminergic neurotoxicity model, djGDNF47 pretreatment improved cell viability and reduced p53 and caspase-3 expression. Intranasally delivered Cy3-djGDNF47 reached the olfactory bulb and persisted for 24 h, while repeated administration increased BrdU+/DCX+ newborn neurons in neurogenic brain regions. Together, these findings identify djGDNF47 as a noninvasively deliverable GDNF-derived peptide with neuroinductive and neuroprotective activity, supporting its further investigation as a candidate neurotrophic therapy for neurodegenerative disorders, including Parkinson's disease.

Keywords: Adult neurogenesis; Glial cell line-derived neurotrophic factor (GDNF); Intranasal drug delivery; Neuroprotection; Neuroregeneration; Parkinson's disease; djGDNF47

DOI: https://doi.org/10.1016/j.ijbiomac.2026.154555

Brain Sci. 2026 Sep 07. pii: 951. [Epub ahead of print]16(9):

Exercise and Productive Hippocampal Neurogenesis After Stroke: From Niche Remodeling to Cognitive Recovery.

Xinzheng Wang, Guohao Yi, Huifen Zhou, Bihan Wang, Qiang Tu.

Post-stroke cognitive impairment (PSCI) is a frequent and disabling consequence of stroke that limits long-term recovery and quality of life. Disruption of the hippocampal neurogenic niche may impair adult hippocampal neurogenesis (AHN), while exercise is increasingly recognized as a promising non-pharmacological strategy for cognitive rehabilitation. This review synthesizes evidence that exercise may shift the post-stroke hippocampal niche from a hostile to a permissive state through coordinated regulation of neuroinflammation, neurovascular integrity, and mitochondrial homeostasis. We distinguish increased progenitor proliferation from productive neurogenesis, defined by the survival, maturation, appropriate positioning, and functional integration of newborn neurons. Exercise may attenuate inflammatory signaling, support angiogenesis and blood-brain barrier repair, and improve mitochondrial biogenesis and quality control; however, much of the mechanistic evidence remains preclinical, and increases in early neurogenic markers do not by themselves establish functional neuronal integration or causality. Current clinical evidence supports cognitive benefits of exercise more strongly than it supports AHN as the indispensable mediator of those benefits. A productive-neurogenesis framework therefore provides a more rigorous basis for interpreting existing studies and designing future experiments that combine lineage tracing, temporally controlled neurogenesis ablation, circuit-level analysis, and domain-specific cognitive outcomes.

Keywords: adult hippocampal neurogenesis; exercise; mitochondrial homeostasis; neuroinflammation; neurovascular unit; post-stroke cognitive impairment

DOI: https://doi.org/10.3390/brainsci16090951

bioRxiv. 2026 Sep 14. pii: 2026.09.08.750063. [Epub ahead of print]

Reduced inhibition of hippocampal adult-born granule cells by parvalbumin interneurons after TBI.

Corwin R Butler, Connor R Squellati, Eric Schnell.

Traumatic brain injury (TBI) is one of the leading causes of acquired temporal lobe epilepsy. TBI drives hippocampal circuit rearrangements that may contribute to increased seizure risk, such as altered inhibitory circuit function and aberrant post-traumatic neurogenesis. In the hippocampal dentate gyrus, adult-born dentate granule cells (DGCs) acquire inhibitory synaptic inputs from parvalbumin-expressing (PV) interneurons early in their maturation. These inputs are important for circuit integration and feedforward inhibition of these neurons. To test whether DGCs born after TBI have functionally altered PV-mediated innervation, we used genetically modified mice, retroviral vectors, and optogenetics to study adult-born and mature DGCs after TBI. Although DGCs born after TBI acquired inhibitory synaptic inputs during their maturation, PV-mediated inhibition of adult-born DGCs was persistently reduced following TBI. This was not observed in mature granule cells and was not due to TBI-induced changes in PV cell density. This deficit in PV-mediated functional innervation was associated with a transient reduction in release probability at these synapses, which normalized as DGCs matured despite ongoing reduction of functional PV input. Surprisingly, although spontaneous inhibitory postsynaptic currents were reduced for mature granule cells after TBI, these were unchanged in adult-born DGCs. Taken together, these data demonstrate distinct differences in the de novo development and maintenance of PV+ synapses in the dentate gyrus after TBI. The addition of neurons with reduced PV+ interneuron-mediated feed-forward inhibition to the dentate gyrus could contribute to hippocampal hyperexcitability after severe brain injury.

Keywords: Adult Neurogenesis; Dentate Gyrus; Hippocampus; Interneurons; Traumatic Brain Injury

DOI: https://doi.org/10.64898/2026.09.08.750063

Photobiomodul Photomed Laser Surg. 2026 Sep 26. 25785478261490751

The Role of Photobiomodulation Therapy in Enhancing Neurogenesis: Mechanisms and Applications.

Wenhao Wang, Qianting Deng, Timon Cheng-Yi Liu, Luodan Yang.

BACKGROUND: Adult neurogenesis, critical for neural repair and functional plasticity, is impaired in neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury (TBI).
OBJECTIVE: This review summarizes the physiological basis of adult neurogenesis and photobiomodulation (PBM) fundamentals, clarifies PBM-induced neurogenesis mechanisms, evaluates its pre-clinical/clinical efficacy and safety, and addresses translational challenges to support clinical translation.
MATERIALS AND METHODS: We synthesized relevant literature, covering adult neurogenesis characteristics, PBM principles/mechanisms, pre-clinical studies in disorder models, clinical safety/efficacy data, and comparisons with conventional neurogenic therapies.
CONCLUSIONS: PBM promotes neurogenesis via regulating neural stem cell activity, mitochondrial function, and oxidative stress. Pre-clinical/clinical evidence confirms its safety and efficacy; despite parameter and long-term safety challenges, it has great potential in neuroregenerative medicine.

Keywords: adult neurogenesis; mitochondrial function; neural stem/progenitor cells; neuroinflammation; photobiomodulation

DOI: https://doi.org/10.1177/25785478261490751

bioRxiv. 2026 Sep 15. pii: 2026.09.11.750834. [Epub ahead of print]

Matrix Viscoelasticity Regulates the Stemness and Multilineage differentiation of Primary Neural Progenitor-Stem Cells in 3D.

Supeng Ding, Joo Ho Kim, Mengke Wang, Luo Gu.

Neural progenitor-stem cells (NPSCs) reside in mechanically dynamic brain microenvironments and give rise to neurons, astrocytes, and oligodendrocytes. Although recent studies have shown that matrix viscoelasticity can influence neural maturation and neurogenic differentiation, its role in primary NPSCs beyond neurogenesis remains less defined. How matrix viscoelasticity or stress relaxation regulates primary NPSC stemness, neuronal and glial differentiation, and the associated matrix-cell mechanotransduction pathways are not well understood. Here, we use alginate hydrogels with independently tunable stiffness and stress relaxation properties to investigate how matrix stress relaxation regulates the fate of primary subventricular zone (SVZ)-derived NPSCs in 3D. The results suggested that matrices with faster stress relaxation enhances stemness maintenance, radial glial-like marker expression, and differentiation of NPSCs toward neuronal, astrocytic, and oligodendrocytic lineages in the corresponding biochemical environments. In mixed neuronal/astrocytic differentiation conditions, fast-relaxing matrices preferentially promote neuronal differentiation. Mechanistically, NPSC responses to matrix stress relaxation involve integrin-mediated adhesion, actomyosin contractility, actin polymerization, and Piezo1 activity, with distinct contributions across differentiation lineages. Together, these findings reveal how matrix stress relaxation regulates primary NPSC stemness and multilineage differentiation through multiple mechanotransduction pathways in 3D.

DOI: https://doi.org/10.64898/2026.09.11.750834