INCyL. Artículos del Instituto de Neurociencias de Castilla y León

Dietary adherence and disability evolution in multiple sclerosis: an exploratory 12-month prospective cohort study

2026-07-08T12:45:31Z

[EN] Background & aims Lifestyle factors may influence disability trajectories in multiple sclerosis (MS), yet prospective data linking sustained dietary adherence to objective clinical outcomes remain limited. Homocysteine, a metabolite involved in one-carbon metabolism, represents a biologically plausible mediator between nutrition and neurodegeneration, although its longitudinal clinical relevance in MS is uncertain. This study aimed to investigate whether adherence to a structured dietary intervention is associated with longitudinal changes in plasma homocysteine levels and disability progression in patients with MS over 12 months. Methods In this prospective cohort study, 41 patients with MS were followed for 12 months. Dietary adherence was quantified using a structured follow-up scale (range 2–6). Plasma homocysteine levels and Expanded Disability Status Scale (EDSS) scores were assessed at baseline, 6 months, and 12 months. Associations between adherence, metabolic changes, and EDSS evolution were evaluated using correlation analyses and multivariate linear regression adjusting for age, sex, BMI, baseline EDSS, and treatment line. Results Baseline mean homocysteine was 10.91 ± 6.94 μmol/L and decreased to 8.24 ± 3.33 μmol/L at 6 months, remaining stable at 8.27 ± 2.42 μmol/L at 12 months. Between-group differences in homocysteine showed a trend toward significance at 12 months (ANOVA p = 0.059). Mean EDSS increased slightly from 1.14 to 1.23 in the overall cohort (p > 0.05). However, EDSS evolution differed according to dietary adherence (ANOVA p = 0.009): low-adherence patients showed a mean EDSS increase (+0.53 ± 0.72), whereas high-adherence patients showed a mean EDSS decrease (−0.56 ± 1.08). Given the low baseline EDSS, short follow-up, and small high-adherence subgroup, these changes should be interpreted as exploratory differences in short-term EDSS trajectory rather than confirmed clinical improvement and do not establish causality. Adherence score was inversely correlated with EDSS change (r = −0.57, p = 0.0006) and remained independently associated in multivariate analysis (β = −0.45, 95% CI −0.68 to −0.22, p = 0.0005). Conclusions Higher adherence to the dietary counselling programme was associated with a more favourable short-term disability trajectory over 12 months. However, causality cannot be inferred, and the clinical significance of these modest changes remains uncertain. Because the adherence score was not formally validated and may partly reflect broader health-related behaviours or engagement with care, and because the dietary intervention was individualized, the study cannot identify specific dietary components or dietary patterns associated with disability trajectories. These exploratory findings require confirmation in larger controlled studies using validated dietary assessment instruments.

Medical dispensation in La Rioja, Spain: epidemiology and its relationship with social determinants: a descriptive study

2026-07-08T12:36:15Z

[EN] Introduction: Spain stands out as the European Union country with the highest life expectancy, reaching 83.2 years in 2022. This context is accompanied by population aging and an increase in chronic and degenerative diseases, which translates into greater medication use. In 2022, the National Health System (NHS) dispensed over 1,127.8 million packages. This study aims to evaluate the state of medication dispensation in La Rioja and its relationship with health determinants such as economic conditions, area of residence, age, and gender.Methods: We conducted an observational, retrospective, cross-sectional study between January 2016 and December 2023. A total of 4,108,656 raw e-dispensations (2016–2023) were recorded, from which 1,433,531 unique patient–ATC4–year records (26 frequent subgroups) were analyzed. We included patients aged 14 years and older with electronic dispensations. Variables analyzed included age, gender, socioeconomic level, type and number of dispensations, and the patient’s basic health zone. Statistical analyses employed Chi-square tests for categorical associations and Kruskal–Wallis tests to compare age distributions across ATC4 medication groups, with a significance level of p < 0.05.Results: Proton pump inhibitors (PPIs) were the most dispensed medications in La Rioja, with 82,195 dispensations between 2016 and 2023, followed by propionic acid derivative anti-inflammatory drugs. Antidepressant dispensations increased from 5,281 in 2016 to 7,486 in 2023. Regarding gender differences, women accounted for more dispensations (53.7%). The largest differences favoring women were observed in thyroid hormones, vitamin D, and antidepressant groups. Conversely, medication groups indicated for cardiovascular pathology—such as platelet aggregation inhibitors and angiotensin-converting enzyme inhibitors—showed a significant difference favoring men. Among the elderly, the most dispensed medications also corresponded to families indicated for cardiovascular diseases. By health zones, PPI dispensation was high and homogeneous in the Rioja 1 and Rioja 2 clusters, while anxiolytics and antidepressants stood out in the municipality of San Román and the Guindalera area of Logroño. In socioeconomic terms, pensioners with limited incomes (IHC 002) primarily consumed PPIs, paracetamol, and benzodiazepines, while low-income workers (IHC 003) showed notable dispensation of propionic acid derivatives, PPIs, and paracetamol.Discussion: Our findings align with national and European trends: PPIs and propionic acid derivative anti-inflammatories are the most frequently dispensed medications. Between 2016 and 2023, we observed an increase in the absolute number of unique users in ATC4 subgroup N06AX (Other antidepressants) (+41.8%) and, to a lesser extent, in N06AB (Selective serotonin reuptake inhibitors) (+25.5%), while the annual relative share of N06AB remained essentially stable. Socioeconomic determinants—such as low income and unemployment—appear to directly influence access to and dispensation of medications.Conclusion: Medication dispensation patterns in La Rioja mirror broader national and EU trends, with PPIs and propionic acid derivatives leading. Gender, age, geographic zone, and socioeconomic status are associated with distinct dispensation profiles. Targeted public health strategies should consider these determinants to optimize rational medication use and equity in access.

Simulation-Based Training for Nursing Students to Improve Patient Safety: Systematic Review

2026-07-08T12:19:04Z

[EN] Background: Patient safety is a fundamental pillar of health care quality. Simulation-based training provides a controlled environment for nursing students to develop safety competencies and error-recognition skills before clinical practice. Objective: This systematic review aimed to describe and characterize the simulation-based education features and modalities used to address patient safety outcomes in undergraduate nursing students, identifying the strategies that contribute to improvements in safety-related competencies. Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines across PubMed, Web of Science, Scopus, CINAHL, Cochrane, and Lilacs (2019‐2024). Inclusion criteria focused on original studies involving undergraduate nursing students and simulation interventions measuring patient safety outcomes. Studies in languages other than English, Spanish, or Portuguese were excluded. Two reviewers independently performed study selection and data extraction. Methodological quality was assessed using Joanna Briggs Institute tools, applying a 60% quality threshold for inclusion. Results were synthesized through a narrative approach. Results: A total of 20 studies from 12 countries were included. The methodological quality was high (n=14) and moderate (n=6). Findings revealed that high-fidelity simulation and virtual reality are the primary strategies used. Simulation proved effective in enhancing both technical skills (medication administration accuracy) and nontechnical skills (communication via SBAR [Situation, Background, Assessment, Recommendation] and ISBAR [Identification, Situation, Background, Assessment, Recommendation] tools, teamwork, and adverse event reporting). Key strategies contributing to safety included repetitive practice and interprofessional simulation, which significantly improved error detection and clinical judgment. Conclusions: Simulation is an essential pedagogical strategy for preparing nursing students to deliver safe care. Practical implications include the need to integrate structured simulation into nursing curricula to bridge the theory-practice gap. Future research should prioritize longitudinal designs to assess the retention of these safety skills in clinical settings and develop standardized metrics for measuring patient safety outcomes.

Activación electromiográfica del miembro inferior durante imaginería motora: de la mente al músculo

2026-06-19T00:00:50Z

[ES]Introducción La imaginería motora (IM) es una herramienta ampliamente utilizada en campos como el deporte o la neurorrehabilitación ya que se ha demostrado que provoca una activación cerebral similar a la que se produce durante el movimiento. Sin embargo, la evidencia sobre su capacidad para inducir activación muscular periférica en el miembro inferior es limitada. El objetivo de este estudio fue analizar la actividad electromiográfica (EMG) durante diferentes condiciones de ejecución real e IM del miembro inferior. Materiales y métodos Participaron 17 adultos sanos, en los que se registró la actividad EMG superficial del recto y el bíceps femoral durante cuatro condiciones: ejecución real e IM guiada de un patrón motor simple (extensión de rodilla) y de un programa motor orientado a objetivo (golpeo de balón). Todos los participantes realizaron una única sesión experimental. La señal EMG se procesó de forma estandarizada y se normalizó respecto al máximo observado durante la ejecución real. Resultados La IM del patrón simple se asoció a incrementos subumbrales, pero significativos de la actividad EMG respecto al reposo, mientras que la IM del programa motor mostró mayor variabilidad interindividual y ausencia de diferencias consistentes frente al nivel basal. No se observaron correlaciones significativas entre la actividad EMG y la capacidad global de IM. Conclusión Estos resultados sugieren que la IM puede inducir activación muscular periférica de baja amplitud, especialmente en tareas motoras simples, mientras que el aumento de la complejidad funcional podría reducir la consistencia de dicha activación.

Ndfip2 in TrkA-expressing sensory neurons regulates noxious mechanosensation through control of TrkA signaling and protein levels

2026-05-21T00:03:02Z

[EN]Nociception, the neural process underlying pain detection, is modulated by the NGF/TrkA signaling axis. Although anti-NGF antibodies can alleviate chronic pain, their clinical application is limited by adverse effects, underscoring the need to identify downstream regulators of this pathway. One such mechanism involves TrkA ubiquitination mediated by Nedd4 E3 ubiquitin ligases, whose activity is modulated by Nedd4 family interacting protein 2 (Ndfip2). Notably, Ndfip2 expression is regulated by TrkA signaling under pain conditions. Here, we characterize the physiological and molecular roles of Ndfip2 in sensory neurons. We demonstrate that Ndfip2 localizes to the endoplasmic reticulum and Golgi apparatus and interacts with TrkA in sensory neurons. Conditional deletion of Ndfip2 in TrkA-expressing cells selectively alters mechanical nociception. Mechanistically, loss of Ndfip2 decreases total TrkA protein levels, downstream activation, and cell-surface exposition, particularly in male-derived dorsal root ganglia neurons. Conversely, Ndfip2 expression reduces mature glycosylated TrkA and promotes the accumulation of non-glycosylated forms, consistent with impaired receptor maturation. Together, these findings identify Ndfip2 as a post-translational regulator of TrkA in TrkA-lineage sensory neurons and establish its in vivo role in mechanical nociception.

Genetically modified bone marrow cells halt mitral cell loss by modulating inflammation and protecting against DNA damage

2026-05-21T00:02:48Z

[EN]Cell therapy is a promising strategy for tackling neurodegenerative diseases. The most outstanding results with this approach usually involve neuroprotection of damaged neurons at risk of death, but only with limited success. Current therapies are often based on the idea of “one gene, one disease, one drug” for single targets, a concept that limits their actual effectiveness. In contrast, combining different strategies can establish an advanced cell therapy that can slow down neuronal degeneration. In this study, we took advantage of the combination of cell and gene therapy, by transplanting bone marrow stem cells genetically modified to overexpress insulin-like growth factor 1 (IGF1) into a model of selective neurodegeneration, the PCD mouse. This animal is characterized by progressive neuronal loss in the olfactory bulb and alterations in IGF1 levels, among other symptoms. Using different techniques (cell cultures, viral transduction, cell transplants, flow cytometry, qPCR, ELISA, immunohistochemistry, advanced image analysis), our findings showed that neuronal death was virtually blocked, even 130 days after cell transplantation, a result clearly more successful than previous studies. The effects of this transplant are based in part on the regulation of neuroinflammation, increasing the proportion of reactive microglia and reducing that of proinflammatory microglia. In addition, IGF1 overexpression dramatically reduced DNA damage in mutant animals via IGF binding protein 3 pathway: this enhances neuroprotection by complementing the basal effect of cell therapy itself. In summary, our work supports the idea that combining therapeutic approaches and their synergies is a more effective tactic for combating neuronal loss.

Audiogenic Kindling Stimulation Fails to Induce Cerebral Overexpression of P-Glycoprotein and Limbic Crises in the GASH/Sal Model of Epilepsy

2026-05-15T00:01:59Z

[EN] Experimental evidence indicates that a high seizure burden can induce cerebral overexpression of P-glycoprotein (P-gp) at the blood–brain barrier, a phenomenon associated with drug-resistant epilepsy under the “transporter hypothesis”, but also at the neuronal level, linked to a reduced seizure threshold, increased seizure severity (SS), status epilepticus (SE), and a high spontaneous death (SD) rate. In contrast, we recently described a progressive reduction in SS and the absence of SE and SD in GASH/Sal hamsters subjected to 45 audiogenic seizures. Here, we examined SS, SE, and the SD, and the expression of P-gp, erythropoietin receptor (EPO-R), hypoxia-inducible factor 1 alpha subunit (HIF-1α) and cyclooxygenase 2 (COX-2), in the brains of GASH/Sal hamsters following 20 audiogenic kindling stimulations (AUK-20). SS was evaluated using the midbrain and limbic severity scales; gene expression was assessed by RT-qPCR and P-gp protein levels were measured by immunohistochemistry and Western blot (IHC/WB) analysis. A modest decrease in midbrain SS was observed, without an increase in the already low limbic SS scores, and no SE or SD events occurred. P-gp levels remained low in both IHC and WB analyses. At the mRNA level, we detected increased EPO-R expression, decreased HIF-1α, and increased COX-2 without an accompanying increased in Abcb1b. Unlike findings from other experimental epilepsy models, AUK-20 in GASH/Sal hamsters does not enhance limbic SS, trigger SE or SD, or induce P-gp overexpression in the brain. Independently of the implications for drug resistance, the lack of cerebral P-gp overexpression without increased SS in the AUK-20-GASH/Sal model supports a potential role of P-gp in modulating seizure severity and epilepsy-associated mortality risk.

Specific Glutamylation Patterns of the Cytoskeleton Confer Neuroresistance to Lobe X of the Cerebellum in a Model of Childhood-Onset Neurodegeneration with Cerebellar Atrophy

2026-05-13T00:01:09Z

[EN]The cytoskeleton relies heavily on the dynamic nature of microtubules, regulated by posttranslational modifications such as polyglutamylation and deglutamylation. Disruption of its internal balance, particularly through the absence of cytosolic carboxypeptidase 1 (CCP1), leads to cytoskeletal collapse and cell death. An example of this occurrence exists in the Purkinje Cell Degeneration (PCD) mouse, a direct animal model for childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) human disease. Both CONDCA patients and PCD mice suffer a dramatic degeneration of Purkinje cells. Intriguingly, lobe X appears less vulnerable to this insult. This study revealed in wild-type mice that lobe X expresses less Ccp1 compared to other lobes, correlating with its delayed degeneration in PCD mice. Further expression analysis of other deglutamylating enzymes (CCP4 and CCP6) and glutamylating enzymes (TTLL1) revealed distinctive patterns: Ccp4 showed minimal relevance in cerebellum, while Ccp6 displayed a compensatory increase during critical stages. Meanwhile, Ttll1 expression remained consistent across lobes, suggesting that the resistance of lobe X may be related to a more dynamic, hyperglutamylated cytoskeleton. Unraveling the neuroresistance mechanisms of Purkinje cells may help mitigate neuronal loss in CONDCA patients and may offer a glimmer of hope for alleviating the symptoms of other neurodegenerative diseases.

Performance assessment of no-fee GNSS augmentation systems for tractor guidance

2026-04-18T00:01:31Z

[EN] This study assesses the performance of no-fee GNSS augmentation systems for tractor guidance. Five no-fee augmentation systems: EGNOS, GLIDE, RTK, VRS-NRTK, and on-site RTK were evaluated in both static and guidance tests over short- and long‑term periods using three GNSS receiver types: low-cost Navilock NL8022MP, mid-range Novatel Smart2, and high-end Harxon TS108PRO. Static tests recorded 24 h of position data from 14 receiver-augmentation configurations on a fixed surface. Guidance tests recorded trajectory data from the 14 configurations during straight-line guidance using a tractor equipped with two GNSS receivers, one under test and one high-precision reference. Results found that: (i) unaugmented GNSS resulted in guidance errors of 2–3 m, reduced below 1 m in pass-to-pass intervals shorter than 15 min; (ii) EGNOS reduced these guidance errors by ∼41%; (iii) GLIDE reduced guidance errors to below 20 cm for pass-to-pass intervals shorter than 15 min, with no long-term improvement; (iv) RTK guidance error decreased as baseline length shortened: >100 km yielded > 17 cm, 20–100 km yielded 3–20 cm, and < 20 km yielded 2–3 cm; (v) VRS-NRTK slightly outperformed RTK with similar baseline lengths; and (vi) on-site RTK enabled 1 cm guidance error. In summary: low-cost receivers without augmentation or with EGNOS result in metre-level errors; mid-range receivers with GLIDE deliver decimetre-level guidance errors in the short term; and high-end receivers using on-site RTK or VRS-NRTK on baselines up to 100 km achieve centimetre-level errors, enabling farmers to replicate tractor trajectories consistently year to year.

Prosodia rítmico frecuencial en lingüística clínica: en búsqueda de biomarcadores fonéticos para alzheimer y depresión mayor

2026-03-19T01:02:54Z

[EN]This paper delves into the prosodic features of speech affected in AD and MD, the type of pathology they are associated with (aphasia, apraxia or aprosodia), as well as the contribution of these alterations to the neurolinguistic field (hemispheric specialization).We used a corpus of spontaneous speech from patients with AD (n=10) and MD (n=10), and a control group with HS (n=10). The results showed a discriminatory significance of VnPVI (in MD), and (Δ)f0 and %V; furthermore, %V is a strong variable to distinguish between speakers with and without pathology, as well as to discriminate between AD and MD along with other variables. There is, however, no correlation with verbal fluency (semantic and phonological) or with MMSE, which would imply a motor type deficit: apraxic type in AD and aprosodic type in MD. These results show certain phonological and typological conditioning, among other issues.

Melatonin at the Crossroads of Oxidative Stress, Immunity, and Cancer Therapy

2026-02-11T01:01:06Z

[EN] Melatonin, an ancient and evolutionarily conserved indolamine, has long attracted attention for its multifunctional roles in redox homeostasis. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly scavenging reactive oxygen and nitrogen species and by upregulating antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. At the same time, it exerts wide-ranging immunomodulatory functions by influencing both innate and adaptive immune responses. All these actions converge within the tumor microenvironment, where oxidative stress and immune suppression drive cancer progression. Although the antitumoral effects of melatonin have traditionally been interpreted through its actions on T cells and NK cells, recent studies identify macrophages as an underappreciated and pivotal target. Notably, melatonin influences macrophage polarization, favoring antitumor M1 phenotypes over pro-tumoral M2 states, while attenuating chronic inflammation and restoring mitochondrial function. This review summarizes current knowledge on melatonin’s antioxidant and immunoregulatory mechanisms, highlighting its impact on the tumor immune microenvironment, with a particular focus on the growing recognition of macrophages as a compelling new axis through which melatonin may exert anticancer effects

HSP25 and HSP25-P-Ser15 Prompt Innate Neuroprotection in Lobe X of the Cerebellum

2026-02-06T01:01:18Z

[EN]The cerebellar cortex presents a repetitive structure, but the main projecting neurons of this tissue, the Purkinje cells, are not identical and behave differently to various types of injury. Common patterns of neurodegeneration exist, where certain Purkinje cells die earlier than others. By contrast, lobe X of the cerebellum is a particularly resistant structure, independently of the cerebellar disease or damage. However, the mechanisms underlying the survival capability of these especially resistant Purkinje cells are still unknown. In this work, we have used the Purkinje Cell Degeneration (PCD) mouse, a model of severe cerebellar degeneration that also reproduces the human disease called childhood-onset neurodegeneration with cerebellar atrophy, to study Purkinje cell resistance. After an exhaustive immunochemical analysis of the different subpopulations of Purkinje cells, the Heat Shock Protein 25 (HSP25) and its phosphorylated version HSP25-P-Ser15 were found to be especially induced in lobe X of PCD mice. As this protein has neuroprotective properties, it may be responsible for resistance against cerebellar neurodegeneration. Taking into account the constant resistance of lobe X, the use of HSP25 may lead to new possibilities for achieving natural protection both in cerebellum and in other brain structures, or even for developing future neuroprotective therapies.

Model of selective neurodegeneration driven by a Ccp1 mutation leads to atypical microglia with an increased response to pathological stimuli

2026-01-22T01:00:58Z

Microglia are the primary immune cells of the central nervous system and maintain tissue homeostasis through phagocytosis and regulation of inflammatory signalling. Although these functions are well established, the molecular mechanisms that control microglial activation during neurodegeneration remain poorly understood. We focused on the Purkinje Cell Degeneration (PCD) mouse, which carries a loss-of-function mutation in Ccp1 that disrupts tubulin post-translational modifications essential for cytoskeletal stability. Because cytoskeletal dynamics are fundamental for microglial motility, phagocytosis, and proliferation, the Ccp1 mutation offers a model to directly examine how intrinsic cytoskeletal defects alter microglial behaviour and how these alterations manifest within regions undergoing distinct patterns of neurodegeneration. To this end, we combined in vitro and in vivo approaches. Microglia were isolated from neonatal cortex and adult cerebellum and olfactory bulb, and microglia-like cells were generated from bone marrow-derived haematopoietic stem cells. In vivo microglial depletion was achieved with the CSF1R inhibitor PLX5622. Immunohistochemistry quantified microglial density, morphology, and marker expression; transcriptomic profiling assessed identity and functional pathways; and functional assays evaluated phagocytosis, motility, and proliferation. Motor behaviour tests were performed to determine whether microglial dysfunction contributes to circuit-level impairments. Statistical analyses used parametric or non-parametric tests according to distribution. Ccp1-deficient microglia exhibited intrinsic deficits in phagocytosis, motility, and proliferation, independent of overt neuronal loss. These impairments were amplified in degenerating regions, where microglia adopted a predominantly anti-inflammatory rather than pro-inflammatory activation profile. This atypical state suggests a maladaptive response that may compromise tissue homeostasis and intensify disease progression. Consistent with this, animals showed altered motor behaviour, indicating functional consequences of microglial dysfunction. Together, these findings identify Ccp1 as a key regulator of microglial homeostasis and demonstrate how cytoskeletal disruption can reshape microglial responses in neurodegenerative environments, providing mechanistic insight and potential therapeutic targets.

Nucleolin reorganization and nucleolar stress in Purkinje cells of mutant PCD mice.

2026-01-22T01:02:13Z

[EN] The Purkinje cell (PC) degeneration (pcd) mouse harbors a mutation in Agtpbp1 gene that encodes for the cytosolic carboxypeptidase, CCP1. The mutation causes degeneration and death of PCs during the postnatal life, resulting in clinical and pathological manifestation of cerebellar ataxia. Monogenic biallelic damaging variants in the Agtpbp1 gene cause infantile-onset neurodegeneration and cerebellar atrophy, linking loss of functional CCP1 with human neurodegeneration. Although CCP1 plays a key role in the regulation of tubulin stabilization, its loss of function in PCs leads to a severe nuclear phenotype with heterochromatinization and accumulation of DNA damage. Therefore, the pcd mice provides a useful neuronal model to investigate nuclear mechanisms involved in neurodegeneration, particularly the nucleolar stress. In this study, we demonstrated that the Agtpbp1 gene mutation induces a p53-dependent nucleolar stress response in PCs, which is characterized by nucleolar fragmentation, nucleoplasmic and cytoplasmic mislocalization of nucleolin, and dysfunction of both pre-rRNA processing and mRNA translation. RT-qPCR analysis revealed reduction of mature 18S rRNA, with a parallel increase of its intermediate 18S-5'-ETS precursor, that correlates with a reduced expression of Fbl mRNA, which encodes an essential factor for rRNA processing. Moreover, nucleolar alterations were accompanied by a reduction of PTEN mRNA and protein levels, which appears to be related to the chromosome instability and accumulation of DNA damage in degenerating PCs. Our results highlight the essential contribution of nucleolar stress to PC degeneration and also underscore the nucleoplasmic mislocalization of nucleolin as a potential indicator of neurodegenerative processes.

Bone marrow cell transplantation restores olfaction in the degenerated olfactory bulb.

2026-01-22T01:02:11Z

[EN] Bone marrow contains heterogeneous cell types including end-lineage cells, committed tissue progenitors, and multipotent stem/progenitor cells. The immense plasticity of bone marrow cells allows them to populate diverse tissues such as the encephalon, and give rise to a variety of cell types. This unique plasticity makes bone marrow-derived cells good candidates for cell therapy aiming at restoring impaired brain circuits. In the present study, bone marrow cells were transplanted into P20 mice that exhibit selective olfactory degeneration in adulthood between P60 and P150. These animals, the so-called Purkinje Cell Degeneration (PCD) mutant mice, suffer from a progressive and specific loss of a subpopulation of principal neurons of the olfactory bulb, the mitral cells (MCs), sparing the other principal neurons, the tufted cells. As such, PCD mice constitute an interesting model to evaluate the specific role of MCs in olfaction and to test the restorative function of transplanted bone marrow-derived cells. Using precision olfactometry, we revealed that mutant mice lacking MCs exhibited a deficit in odorant detection and discrimination. Remarkably, the transplantation of wild-type bone marrow-derived cells into irradiated PCD mutant mice generated a large population of microglial cells in the olfactory bulb and reduced the degenerative process. The alleviation of MC loss in transplanted mice was accompanied by functional recovery witnessed by significantly improved olfactory detection and enhanced odor discrimination. Together, these data suggest that: (1) bone marrow-derived cells represent an effective neuroprotective tool to restore degenerative brain circuits, and (2) MCs are necessary to encode odor concentration and odor identity in the mouse olfactory bulb.

The olfactory system as a puzzle: playing with its pieces.

2026-01-22T01:02:10Z

The mammalian olfactory bulb (OB) has all the features of a whole mammalian brain but in a more reduced space: neuronal lamination, sensory inputs, afferences, or efferences to other centers of the central nervous system, or a contribution of new neural elements. Therefore, it is widely considered as "a brain inside the brain." Although this rostral region has the same origin and general layering as the other cerebral cortices, some distinctive features make it very profitable in experimentation in neurobiology: the sensory inputs are driven directly on its surface, the main output can be accessed anatomically, and new elements appear in it throughout adult life. These three morphological characteristics have been manipulated to analyze further the response of the whole OB. The present review offers a general outlook into the consequences of such experimentation in the anatomy, connectivity and neurochemistry of the OB after (a) sensory deprivation, mainly by naris occlusion; (b) olfactory deinnervation by means of olfactory epithelium damage, olfactory nerve interruption, or even olfactory tract disruption; (c) the removal of the principal neurons of the OB; and (d) management of the arrival of newborn interneurons from the rostral migratory stream. These experiments were performed using surgical or chemical methods, but also by means of the analysis of genetic models, some of whose olfactory components are missing, colorless or mismatching within the wild-type scenario of odor processing.