Frontiers in NeuroanatomyPub Date : 2024-08-14eCollection Date: 2024-01-01DOI: 10.3389/fnana.2024.1362165
Pedro Renato Brandão, Danilo Assis Pereira, Talyta Cortez Grippe, Diógenes Diego de Carvalho Bispo, Fernando Bisinoto Maluf, Ricardo Titze-de-Almeida, Brenda Macedo de Almeida E Castro, Renato Puppi Munhoz, Maria Clotilde Henriques Tavares, Francisco Cardoso
{"title":"Mapping brain morphology to cognitive deficits: a study on PD-CRS scores in Parkinson's disease with mild cognitive impairment.","authors":"Pedro Renato Brandão, Danilo Assis Pereira, Talyta Cortez Grippe, Diógenes Diego de Carvalho Bispo, Fernando Bisinoto Maluf, Ricardo Titze-de-Almeida, Brenda Macedo de Almeida E Castro, Renato Puppi Munhoz, Maria Clotilde Henriques Tavares, Francisco Cardoso","doi":"10.3389/fnana.2024.1362165","DOIUrl":"10.3389/fnana.2024.1362165","url":null,"abstract":"<p><strong>Background: </strong>The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort.</p><p><strong>Materials and methods: </strong>This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (<i>n</i> = 36) and PD-MCI (<i>n</i> = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer.</p><p><strong>Results: </strong>Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm<sup>2</sup> cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions.</p><p><strong>Conclusion: </strong>PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1362165"},"PeriodicalIF":2.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yukari Shigemoto-Mogami, Kimiko Nakayama-Kitamura, Kaoru Sato
{"title":"The arrangements of the microvasculature and surrounding glial cells are linked to blood–brain barrier formation in the cerebral cortex","authors":"Yukari Shigemoto-Mogami, Kimiko Nakayama-Kitamura, Kaoru Sato","doi":"10.3389/fnana.2024.1438190","DOIUrl":"https://doi.org/10.3389/fnana.2024.1438190","url":null,"abstract":"The blood–brain barrier (BBB) blocks harmful substances from entering the brain and dictates the central nervous system (CNS)-specific pharmacokinetics. Recent studies have shown that perivascular astrocytes and microglia also control BBB functions, however, information about the formation of BBB glial architecture remains scarce. We investigated the time course of the formation of BBB glial architecture in the rat brain cerebral cortex using Evans blue (EB) and tissue fixable biotin (Sulfo-NHS Biotin). The extent of the leakage into the brain parenchyma showed that the BBB was not formed at postnatal Day 4 (P4). The BBB gradually strengthened and reached a plateau at P15. We then investigated the changes in the configurations of blood vessels, astrocytes, and microglia with age by 3D image reconstruction of the immunohistochemical data. The endfeet of astrocytes covered the blood vessels, and the coverage rate rapidly increased after birth and reached a plateau at P15. Interestingly, microglia were also in contact with the capillaries, and the coverage rate was highest at P15 and stabilized at P30. It was also clarified that the microglial morphology changed from the amoeboid type to the ramified type, while the areas of the respective contact sites became smaller during P4 and P15. These results suggest that the perivascular glial architecture formation of the rat BBB occurs from P4 to P15 because the paracellular transport and the arrangements of perivascular glial cells at P15 are totally the same as those of P30. In addition, the contact style of perivascular microglia dramatically changed during P4-P15.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"369 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Understanding subcortical projections to the lateral posterior thalamic nucleus and its subregions using retrograde neural tracing","authors":"Hisashi Nakamura, Keisuke Ohta","doi":"10.3389/fnana.2024.1430636","DOIUrl":"https://doi.org/10.3389/fnana.2024.1430636","url":null,"abstract":"The rat lateral posterior thalamic nucleus (LP) is composed of the rostromedial (LPrm), lateral (LPl), and caudomedial parts, with LPrm and LPl being areas involved in information processing within the visual cortex. Nevertheless, the specific differences in the subcortical projections to the LPrm and LPl remain elusive. In this study, we aimed to reveal the subcortical regions that project axon fibers to the LPl and LPrm using a retrograde neural tracer, Fluorogold (FG). After FG injection into the LPrm or LPl, the area was visualized immunohistochemically. Retrogradely labeled neurons from the LPrm were distributed in the retina and the region from the diencephalon to the medulla oblongata. Diencephalic labeling was found in the reticular thalamic nucleus (Rt), zona incerta (ZI), ventral lateral geniculate nucleus (LGv), intergeniculate leaflet (IGL), and hypothalamus. In the midbrain, prominent labeling was found in the periaqueductal gray (PAG) and deep layers of the superior colliculus. Additionally, retrograde labeling was observed in the cerebellar and trigeminal nuclei. When injected into the LPl, several cell bodies were labeled in the visual-related regions, including the retina, LGv, IGL, and olivary pretectal nucleus (OPT), as well as in the Rt and anterior pretectal nucleus (APT). Less labeling was found in the cerebellum and medulla oblongata. When the number of retrogradely labeled neurons from the LPrm or LPl was compared as a percentage of total subcortical labeling, a larger percentage of subcortical inputs to the LPl included projections from the APT, OPT, and Rt, whereas a large proportion of subcortical inputs to the LPrm originated from the ZI, reticular formation, and PAG. These results suggest that LPrm not only has visual but also multiple sensory-and motor-related functions, whereas the LPl takes part in a more visual-specific role. This study enhances our understanding of subcortical neural circuits in the thalamus and may contribute to our exploration of the mechanisms and disorders related to sensory perception and sensory-motor integration.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"79 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ishan R. Perera, Malek Zahed, Sydney Moriarty, Zachary Simmons, Maya Rodriguez, Courtney Botkin, Taylor Dickson, Bradley Kasper, Kendyl Fahmy, Jonathan A. Millard
{"title":"Geometric morphometric analysis of the brainstem and cerebellum in Chiari I malformation","authors":"Ishan R. Perera, Malek Zahed, Sydney Moriarty, Zachary Simmons, Maya Rodriguez, Courtney Botkin, Taylor Dickson, Bradley Kasper, Kendyl Fahmy, Jonathan A. Millard","doi":"10.3389/fnana.2024.1434017","DOIUrl":"https://doi.org/10.3389/fnana.2024.1434017","url":null,"abstract":"BackgroundChiari I malformation (CMI) is characterized by inferior descent of the cerebellar tonsils through the foramen magnum and is associated with headache and neck pain. Many morphometric research efforts have aimed to describe CMI anatomy in the midsagittal plane using classical measurement techniques such as linear dimensions and angles. These methods are less frequently applied to parasagittal features and may fall short in quantifying more intricate anatomy with fewer distinct homologous landmarks.MethodsLandmark-based geometric morphometric techniques were used to asses CMI morphology in five anatomical planes of interest.ResultsSignificant shape differences between CMI and age/sex-matched controls were found in the midsagittal (Pseudo-<jats:italic>F</jats:italic> = 5.4841, <jats:italic>p</jats:italic> = 0.001) and axial planes through the rostral medulla (Pseudo-<jats:italic>F</jats:italic> = 7.6319, <jats:italic>p</jats:italic> = 0.001). In addition to tonsillar descent, CMI principal component 1 (PC1) scores in the midsagittal protocol were associated with marked anterior concavity of the brainstem and generalized verticality of the cerebellum with anterior rotation of its anterior lobe. In the axial medulla/cerebellum protocol, CMI PC1 scores were associated with greater anterior–posterior (A-P) dimension with loss of medial-lateral (M-L) dimension.DiscussionThese results suggest that CMI is associated with greater curvature of the brainstem and spinal cord, which may perturb normal neural activities and disrupt cerebrospinal fluid movements. Previous reports on the A-P diameter of the posterior fossa in CMI have conflicted; our findings of greater A-P cerebellar dimensionality with concomitant loss of width alludes to the possibility that more caudal aspects of the posterior cranial fossa are more bowl-like (homogenous in axial dimensions) and less trough-like or elongated in the M-L direction.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"472 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alin Horatiu Nedelcu, Vasile Valeriu Lupu, Ancuta Lupu, Razvan Tudor Tepordei, Ileana Ioniuc, Cristinel Ionel Stan, Simona Alice Partene Vicoleanu, Ana Maria Haliciu, Gabriel Statescu, Manuela Ursaru, Ciprian Danielescu, Cristina Claudia Tarniceriu
{"title":"Triangular fossa of the third cerebral ventricle – an original 3D model and morphometric study","authors":"Alin Horatiu Nedelcu, Vasile Valeriu Lupu, Ancuta Lupu, Razvan Tudor Tepordei, Ileana Ioniuc, Cristinel Ionel Stan, Simona Alice Partene Vicoleanu, Ana Maria Haliciu, Gabriel Statescu, Manuela Ursaru, Ciprian Danielescu, Cristina Claudia Tarniceriu","doi":"10.3389/fnana.2024.1398858","DOIUrl":"https://doi.org/10.3389/fnana.2024.1398858","url":null,"abstract":"IntroductionThe triangular recess (TR), also called triangular fossa or <jats:italic>vulva cerebri,</jats:italic> represents the anterior extension of the diencephalic ventricle, located between the anterior columns of the fornix and the anterior white commissure. Over time, this structure of the third cerebral ventricle generated many disputes. While some anatomists support its presence, others have opposite opinions, considering that it only becomes visible under certain conditions. The aim of the study is to demonstrate the tangible structure of the triangular recess. Secondly, the quantitative analysis allowed us to establish an anatomical morphometric standard, as well as the deviations from the standard.Materials and methodsOur study is both a quantitative and a qualitative evaluation of the triangular fossa. We dissected 100 non-neurological adult brains, which were fixed in 10% formaldehyde solution for 10 weeks. The samples are part of the collection of the Institute of Anatomy, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi. We highlighted the triangular fossa by performing dissections in two stages at the level of the roof of the III ventricle.ResultsThe qualitative analysis is a re-evaluation of the classical data concerning the anatomy of the fossa triangularis. We proposed an original 3D model of the triangular recess in which we described a superficial part called vestibule and a deep part called <jats:italic>pars profunda</jats:italic>. We measured the sides of the communication between the two proposed segments, as well as the communication with the III ventricle. By applying the Heron’s formula, we calculated the area of the two communications. Statistical evaluations have shown that these communications are higher than they are wide. In addition, there is a statistical difference between the surfaces of the two communications: 34.07 mm<jats:sup>2</jats:sup> ± 7.01 vs. 271.43 mm<jats:sup>2</jats:sup> ± 46.36 (<jats:italic>p</jats:italic> = 0.001).ConclusionThe outcome of our study is both qualitative and quantitative. Firstly, we demonstrated the existence of the triangular fossa and we conceived a spatial division of this structure. Secondly, the measurements carried out establish an anatomo-morphometric norm of the triangular recess, which is useful in assessing the degree of hydrocephalus during the third endoscopic ventriculoscopy.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"176 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matija Vid Prkačin, Zdravko Petanjek, Ivan Banovac
{"title":"Frontiers | A novel approach to cytoarchitectonics: developing an objective framework for the morphological analysis of the cerebral cortex","authors":"Matija Vid Prkačin, Zdravko Petanjek, Ivan Banovac","doi":"10.3389/fnana.2024.1441645","DOIUrl":"https://doi.org/10.3389/fnana.2024.1441645","url":null,"abstract":"IntroductionThe cytoarchitectonic boundaries between cortical regions and layers are usually defined by the presence or absence of certain cell types. However, these cell types are often not clearly defined and determining the exact boundaries of regions and layers can be challenging. Therefore, in our research, we attempted to define cortical regions and layers based on clear quantitative criteria.MethodsWe performed immunofluorescent anti-NeuN labelling on five adult human brains in three cortical regions—Brodmann areas (BA) 9, 14r, and 24. We reconstructed the cell bodies of 90,723 NeuN-positive cells and analyzed their morphometric characteristics by cortical region and layer. We used a supervised neural network prediction algorithm to classify the reconstructions into morphological cell types. We used the results of the prediction algorithm to determine the proportions of different cell types in BA9, BA14r and BA24.ResultsOur analysis revealed that the cytoarchitectonic descriptions of BA9, BA14r and BA24 were reflected in the morphometric measures and cell classifications obtained by the prediction algorithm. BA9 was characterized by the abundance of large pyramidal cells in layer III, BA14r was characterized by relatively smaller and more elongated cells compared to BA9, and BA24 was characterized by the presence of extremely elongated cells in layer V as well as relatively higher proportions of irregularly shaped cells.DiscussionThe results of the prediction model agreed well with the qualitative expected cytoarchitectonic descriptions. This suggests that supervised machine learning could aid in defining the morphological characteristics of the cerebral cortex.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"57 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anatomical topology of extrahippocampal projections from dorsoventral CA pyramidal neurons in mice","authors":"Junseop Lee, Jeongrak Park, Minseok Jeong, Seo-Jin Oh, Jong-Hyuk Yoon, Yong-Seok Oh","doi":"10.3389/fnana.2024.1421034","DOIUrl":"https://doi.org/10.3389/fnana.2024.1421034","url":null,"abstract":"The hippocampus primarily functions through a canonical trisynaptic circuit, comprised of dentate granule cells and CA1-CA3 pyramidal neurons (PNs), which exhibit significant heterogeneity along the dorsoventral axis. Among these, CA PNs are known to project beyond the hippocampus into various limbic areas, critically influencing cognitive and affective behaviors. Despite accumulating evidence of these extrahippocampal projections, the specific topological patterns—particularly variations among CA PN types and between their dorsal and ventral subpopulations within each type—remain to be fully elucidated. In this study, we utilized cell type-specific Cre mice injected with fluorescent protein-expressing AAVs to label each CA PN type distinctly. This method further enabled the dual-fluorescence labeling of dorsal and ventral subpopulations using EGFP and tdTomato, respectively, allowing a comprehensive comparison of their axonal projections in an animal. Our findings demonstrate that CA1 PNs predominantly form unilateral projections to the frontal cortex (PFC), amygdala (Amy), nucleus accumbens (NAc), and lateral septum (LS), unlike CA2 and CA3 PNs making bilateral innervation to the LS only. Moreover, the innervation patterns especially within LS subfields differ according to the CA PN type and their location along the dorsoventral axis of the hippocampus. This detailed topographical mapping provides the neuroanatomical basis of the underlying functional distinctions among CA PN types.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"73 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cajal and his love for Nature: a sentimental essence in the legacy of neurosciences","authors":"Eduardo Garrido","doi":"10.3389/fnana.2024.1408783","DOIUrl":"https://doi.org/10.3389/fnana.2024.1408783","url":null,"abstract":"Santiago Ramón y Cajal (1852–1934) revolutionized the branches of neuroscience in a forceful way, and he did it with extreme delicacy and candor. His scientific writings and drawings are full of allusions to Nature, a fact that demonstrates how he saw, understood and enjoyed it with exquisite sensitivity and pressing emotion. Neuroscience awakened in him the utmost curiosity to delve into the powerful mysteries of the mind, and neurohistology allowed him to satisfy his deepest concerns for fascinating scenarios, a desire not sufficiently fulfilled throughout the fields, mountains and forests of his childhood and youth. Through that wonderful microscopic world Cajal changed the size of the dreamed landscapes but not the dimension of the longed-for adventures. Exploring and entering unknown paths he unraveled some of the greatest enigmas that the nervous system hid, but he would do so with a deep feeling toward the infinite beauty that Nature itself offered him. In short, Nature was the vital axis of Cajal’s overwhelming and complex personality, his most genuine essence and the inexhaustible source of inspiration where he poured his imagination and fantasy. He became a vocational adventurer, an insatiable explorer, a talented artist and an exquisite humanist. An eminently romantic soul who knew how to link Nature and Neuroscience with unconditional and perpetual emotionality.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"37 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alia M. Obeidat, Shingo Ishihara, Jun Li, Natalie S. Adamczyk, Lindsey Lammlin, Lucas Junginger, Tristan Maerz, Richard J. Miller, Rachel E. Miller, Anne-Marie Malfait
{"title":"Intra-articular sprouting of nociceptors accompanies progressive osteoarthritis: comparative evidence in four murine models","authors":"Alia M. Obeidat, Shingo Ishihara, Jun Li, Natalie S. Adamczyk, Lindsey Lammlin, Lucas Junginger, Tristan Maerz, Richard J. Miller, Rachel E. Miller, Anne-Marie Malfait","doi":"10.3389/fnana.2024.1429124","DOIUrl":"https://doi.org/10.3389/fnana.2024.1429124","url":null,"abstract":"ObjectiveKnee joints are densely innervated by nociceptors. In human knees and rodent models, sprouting of nociceptors has been reported in late-stage osteoarthritis (OA). Here, we sought to describe progressive nociceptor remodeling in early and late-stage OA, using four distinct experimental mouse models.MethodsSham surgery, destabilization of the medial meniscus (DMM), partial meniscectomy (PMX), or non-invasive anterior cruciate ligament rupture (ACLR) was performed in the right knee of 10-12-week old male C57BL/6 Na<jats:sub>V</jats:sub>1.8-tdTomato mice. Mice were euthanized (1) 4, 8 or 16 weeks after DMM or sham surgery; (2) 4 or 12 weeks after PMX or sham; (3) 1 or 4 weeks after ACLR injury or sham. Additionally, a cohort of naïve male wildtype mice was evaluated at age 6 and 24 months. Mid-joint cryosections were assessed qualitatively and quantitatively for Na<jats:sub>V</jats:sub>1.8+ or PGP9.5+ innervation. Cartilage damage, synovitis, and osteophytes were assessed.ResultsProgressive OA developed in the medial compartment after DMM, PMX, and ACLR. Synovitis and associated neo-innervation of the synovium by nociceptors peaked in early-stage OA. In the subchondral bone, channels containing sprouting nociceptors appeared early, and progressed with worsening joint damage. Two-year old mice developed primary OA in the medial and the lateral compartment, accompanied by nociceptor sprouting in the synovium and the subchondral bone. All four models showed increased nerve signal in osteophytes.ConclusionThese findings suggest that anatomical neuroplasticity of nociceptors is intrinsic to OA pathology. The detailed description of innervation of the OA joint and its relationship to joint damage might help in understanding OA pain.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"74 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141720765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Livia Testa, Sofia Dotta, Alessandro Vercelli, Letizia Marvaldi
{"title":"Communicating pain: emerging axonal signaling in peripheral neuropathic pain","authors":"Livia Testa, Sofia Dotta, Alessandro Vercelli, Letizia Marvaldi","doi":"10.3389/fnana.2024.1398400","DOIUrl":"https://doi.org/10.3389/fnana.2024.1398400","url":null,"abstract":"Peripheral nerve damage often leads to the onset of neuropathic pain (NeuP). This condition afflicts millions of people, significantly burdening healthcare systems and putting strain on families’ financial well-being. Here, we will focus on the role of peripheral sensory neurons, specifically the Dorsal Root Ganglia neurons (DRG neurons) in the development of NeuP. After axotomy, DRG neurons activate regenerative signals of axons-soma communication to promote a gene program that activates an axonal branching and elongation processes. The results of a neuronal morphological cytoskeleton change are not always associated with functional recovery. Moreover, any axonal miss-targeting may contribute to NeuP development. In this review, we will explore the epidemiology of NeuP and its molecular causes at the level of the peripheral nervous system and the target organs, with major focus on the neuronal cross-talk between intrinsic and extrinsic factors. Specifically, we will describe how failures in the neuronal regenerative program can exacerbate NeuP.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"23 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}