Pub Date : 2024-08-07DOI: 10.3389/fnana.2024.1434017
Ishan R. Perera, Malek Zahed, Sydney Moriarty, Zachary Simmons, Maya Rodriguez, Courtney Botkin, Taylor Dickson, Bradley Kasper, Kendyl Fahmy, Jonathan A. Millard
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-F = 5.4841, p = 0.001) and axial planes through the rostral medulla (Pseudo-F = 7.6319, p = 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-07-29DOI: 10.3389/fnana.2024.1398858
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
IntroductionThe triangular recess (TR), also called triangular fossa or vulva cerebri, 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 pars profunda. 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 mm2 ± 7.01 vs. 271.43 mm2 ± 46.36 (p = 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-07-26DOI: 10.3389/fnana.2024.1441645
Matija Vid Prkačin, Zdravko Petanjek, Ivan Banovac
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.
{"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":null,"pages":null},"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}
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.
海马主要通过由齿状颗粒细胞和 CA1-CA3 锥体神经元（PNs）组成的典型三突触回路发挥功能。其中，CA锥体神经元已知可投射到海马以外的各种边缘区域，对认知和情感行为产生重要影响。尽管有越来越多的证据表明这些海马体外投射，但具体的拓扑模式，尤其是 CA PN 类型之间及其背腹亚群之间的差异，仍有待全面阐明。在本研究中，我们利用细胞特异性 Cre 小鼠，注射了表达荧光蛋白的 AAV，对每种 CA PN 类型进行了标记。这种方法还能分别使用 EGFP 和 tdTomato 对背侧亚群和腹侧亚群进行双重荧光标记，从而对动物体内的轴突投射进行全面比较。我们的研究结果表明，CA1 PNs主要形成单侧投射到额叶皮层（PFC）、杏仁核（Amy）、伏隔核（NAc）和外侧隔（LS），而不像CA2和CA3 PNs只形成对LS的双侧神经支配。此外，根据 CA PN 的类型及其沿海马背腹轴的位置，尤其是 LS 亚区内的神经支配模式也有所不同。这种详细的地形图为 CA PN 类型之间的潜在功能区别提供了神经解剖学基础。
{"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":null,"pages":null},"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}
Pub Date : 2024-07-18DOI: 10.3389/fnana.2024.1408783
Eduardo Garrido
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-07-16DOI: 10.3389/fnana.2024.1430790
V. Antipova, Diana Heimes, Katharina Seidel, Jennifer Schulz, Oliver Schmitt, Carsten Holzmann, Arndt Rolfs, Hans-Jürgen Bidmon, Estibaliz González de San Román Martín, Pitter F. Huesgen, Katrin Amunts, Jonas Keiler, Niels Hammer, Martin Witt, A. Wree
Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1−/− mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1−/− mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced.In order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods.In the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1−/− mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures.Volumes of brain areas of Npc1−/− mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1−/− mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.
{"title":"Differently increased volumes of multiple brain areas in Npc1 mutant mice following various drug treatments","authors":"V. Antipova, Diana Heimes, Katharina Seidel, Jennifer Schulz, Oliver Schmitt, Carsten Holzmann, Arndt Rolfs, Hans-Jürgen Bidmon, Estibaliz González de San Román Martín, Pitter F. Huesgen, Katrin Amunts, Jonas Keiler, Niels Hammer, Martin Witt, A. Wree","doi":"10.3389/fnana.2024.1430790","DOIUrl":"https://doi.org/10.3389/fnana.2024.1430790","url":null,"abstract":"Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1−/− mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1−/− mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced.In order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods.In the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1−/− mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures.Volumes of brain areas of Npc1−/− mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1−/− mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641347","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}
Pub Date : 2024-07-15DOI: 10.3389/fnana.2024.1429124
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
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 NaV1.8-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 NaV1.8+ 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-07-09DOI: 10.3389/fnana.2024.1398400
Livia Testa, Sofia Dotta, Alessandro Vercelli, Letizia Marvaldi
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-07-09DOI: 10.3389/fnana.2024.1422403
Lixin Wang, Yvette Taché
IntroductionThe distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroanatomical tracing to the mouse proximal colon has not been studied in details. This study aimed to trace the locations of extrinsic neurons projecting to the mouse proximal colon compared to the distal colon using dual retrograde tracing.MethodsThe parasympathetic and sensory neurons projecting to colon were assessed using Cholera Toxin subunit B conjugated to Alexa-Fluor 488 or 555 injected in the proximal and distal colon of the same mice.ResultsRetrograde tracing from the proximal and distal colon labeled neurons in the dorsal motor nucleus of the vagus (DMV) and the nodose ganglia, while the tracing from the distal colon did not label the parasympathetic neurons in the lumbosacral spinal cord at L6-S1. Neurons in the pelvic ganglia which were cholinergic projected to the distal colon. There were more neurons in the DMV and nodose ganglia projecting to the proximal than distal colon. The right nodose ganglion had a higher number of neurons than the left ganglion innervating the proximal colon. In the dorsal root ganglia (DRG), the highest number of neurons traced from the distal colon were at L6, and those from the proximal colon at T12. DRG neurons projected closely to the cholinergic neurons in the intermediolateral column of L6 spinal cord. Small percentages of neurons with dual projections to both the proximal and distal colon existed in the DMV, nodose ganglia and DRG. We also observed long projecting neurons traced from the caudal distal colon to the transverse and proximal colon, some of which were calbindin immunoreactive, while there were no retrogradely labeled neurons traced from the proximal to distal colon.DiscussionThese data demonstrated that the vagal motor and motor and sensory neurons innervate both the proximal and distal colon in mice, and the autonomic neurons in the intermediate zone of the lumbosacral spinal cord do not project directly to the mouse colon, which differs from that in humans.
{"title":"The parasympathetic and sensory innervation of the proximal and distal colon in male mice","authors":"Lixin Wang, Yvette Taché","doi":"10.3389/fnana.2024.1422403","DOIUrl":"https://doi.org/10.3389/fnana.2024.1422403","url":null,"abstract":"IntroductionThe distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroanatomical tracing to the mouse proximal colon has not been studied in details. This study aimed to trace the locations of extrinsic neurons projecting to the mouse proximal colon compared to the distal colon using dual retrograde tracing.MethodsThe parasympathetic and sensory neurons projecting to colon were assessed using Cholera Toxin subunit B conjugated to Alexa-Fluor 488 or 555 injected in the proximal and distal colon of the same mice.ResultsRetrograde tracing from the proximal and distal colon labeled neurons in the dorsal motor nucleus of the vagus (DMV) and the nodose ganglia, while the tracing from the distal colon did not label the parasympathetic neurons in the lumbosacral spinal cord at L6-S1. Neurons in the pelvic ganglia which were cholinergic projected to the distal colon. There were more neurons in the DMV and nodose ganglia projecting to the proximal than distal colon. The right nodose ganglion had a higher number of neurons than the left ganglion innervating the proximal colon. In the dorsal root ganglia (DRG), the highest number of neurons traced from the distal colon were at L6, and those from the proximal colon at T12. DRG neurons projected closely to the cholinergic neurons in the intermediolateral column of L6 spinal cord. Small percentages of neurons with dual projections to both the proximal and distal colon existed in the DMV, nodose ganglia and DRG. We also observed long projecting neurons traced from the caudal distal colon to the transverse and proximal colon, some of which were calbindin immunoreactive, while there were no retrogradely labeled neurons traced from the proximal to distal colon.DiscussionThese data demonstrated that the vagal motor and motor and sensory neurons innervate both the proximal and distal colon in mice, and the autonomic neurons in the intermediate zone of the lumbosacral spinal cord do not project directly to the mouse colon, which differs from that in humans.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576111","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}
Pub Date : 2024-07-04DOI: 10.3389/fnana.2024.1426042
Cintia Klaudia Finszter, Róbert Kemecsei, Gergely Zachar, Ágota Ádám, András Csillag
Gestational exposure to valproic acid (VPA) is a valid rodent model of human autism spectrum disorder (ASD). VPA treatment is known to bring about specific behavioral deficits of sociability, matching similar alterations in human autism. Previous quantitative morphometric studies from our laboratory showed a marked reduction and defasciculation of the mesotelencephalic dopaminergic pathway of VPA treated mice, along with a decrease in tissue dopamine in the nucleus accumbens (NAc), but not in the caudatoputamen (CPu). In the present study, the correlative distribution of tyrosine hydroxylase positive (TH+) putative axon terminals, presynaptic to the target neurons containing calretinin (CR) or calbindin (CB), was assessed using double fluorescent immunocytochemistry and confocal laser microscopy in two dopamine recipient forebrain regions, NAc and olfactory tubercle (OT) of neonatal mice (mothers injected with VPA on ED13.5, pups investigated on PD7). Representative image stacks were volumetrically analyzed for spatial proximity and abundance of presynaptic (TH+) and postsynaptic (CR+, CB+) structures with the help of an Imaris (Bitplane) software. In VPA mice, TH/CR juxtapositions were reduced in the NAc, whereas the TH/CB juxtapositions were impoverished in OT. Volume ratios of CR+ and CB+ elements remained unchanged in NAc, whereas that of CB+ was markedly reduced in OT; here the abundance of TH+ axons was also diminished. CR and CB were found to partially colocalize with TH in the VTA and SN. In VPA exposed mice, the abundance of CR+ (but not CB+) perikarya increased both in VTA and SN, however, this upregulation was not mirrored by an increase of the number of CR+/TH+ double labeled cells. The observed reduction of total CB (but not of CB+ perikarya) in the OT of VPA exposed animals signifies a diminished probability of synaptic contacts with afferent TH+ axons, presumably by reducing the available synaptic surface. Altered dopaminergic input to ventrobasal forebrain targets during late embryonic development will likely perturb the development and consolidation of neural and synaptic architecture, resulting in lasting changes of the neuronal patterning (detected here as reduced synaptic input to dopaminoceptive interneurons) in ventrobasal forebrain regions specifically involved in motivation and reward.
{"title":"Gestational VPA exposure reduces the density of juxtapositions between TH+ axons and calretinin or calbindin expressing cells in the ventrobasal forebrain of neonatal mice","authors":"Cintia Klaudia Finszter, Róbert Kemecsei, Gergely Zachar, Ágota Ádám, András Csillag","doi":"10.3389/fnana.2024.1426042","DOIUrl":"https://doi.org/10.3389/fnana.2024.1426042","url":null,"abstract":"Gestational exposure to valproic acid (VPA) is a valid rodent model of human autism spectrum disorder (ASD). VPA treatment is known to bring about specific behavioral deficits of sociability, matching similar alterations in human autism. Previous quantitative morphometric studies from our laboratory showed a marked reduction and defasciculation of the mesotelencephalic dopaminergic pathway of VPA treated mice, along with a decrease in tissue dopamine in the nucleus accumbens (NAc), but not in the caudatoputamen (CPu). In the present study, the correlative distribution of tyrosine hydroxylase positive (TH+) putative axon terminals, presynaptic to the target neurons containing calretinin (CR) or calbindin (CB), was assessed using double fluorescent immunocytochemistry and confocal laser microscopy in two dopamine recipient forebrain regions, NAc and olfactory tubercle (OT) of neonatal mice (mothers injected with VPA on ED13.5, pups investigated on PD7). Representative image stacks were volumetrically analyzed for spatial proximity and abundance of presynaptic (TH+) and postsynaptic (CR+, CB+) structures with the help of an Imaris (Bitplane) software. In VPA mice, TH/CR juxtapositions were reduced in the NAc, whereas the TH/CB juxtapositions were impoverished in OT. Volume ratios of CR+ and CB+ elements remained unchanged in NAc, whereas that of CB+ was markedly reduced in OT; here the abundance of TH+ axons was also diminished. CR and CB were found to partially colocalize with TH in the VTA and SN. In VPA exposed mice, the abundance of CR+ (but not CB+) perikarya increased both in VTA and SN, however, this upregulation was not mirrored by an increase of the number of CR+/TH+ double labeled cells. The observed reduction of total CB (but not of CB+ perikarya) in the OT of VPA exposed animals signifies a diminished probability of synaptic contacts with afferent TH+ axons, presumably by reducing the available synaptic surface. Altered dopaminergic input to ventrobasal forebrain targets during late embryonic development will likely perturb the development and consolidation of neural and synaptic architecture, resulting in lasting changes of the neuronal patterning (detected here as reduced synaptic input to dopaminoceptive interneurons) in ventrobasal forebrain regions specifically involved in motivation and reward.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141548889","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：