Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice
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{"title"=>"Selective vulnerability of spinal and cortical motor neuron subpopulations in delta7 SMA mice", "type"=>"journal", "authors"=>[{"first_name"=>"Paolo", "last_name"=>"D'Errico", "scopus_author_id"=>"55180746700"}, {"first_name"=>"Marina", "last_name"=>"Boido", "scopus_author_id"=>"8847781200"}, {"first_name"=>"Antonio", "last_name"=>"Piras", "scopus_author_id"=>"57197006767"}, {"first_name"=>"Valeria", "last_name"=>"Valsecchi", "scopus_author_id"=>"23010789300"}, {"first_name"=>"Elena", "last_name"=>"De Amicis", "scopus_author_id"=>"55995700800"}, {"first_name"=>"Denise", "last_name"=>"Locatelli", "scopus_author_id"=>"35074567000"}, {"first_name"=>"Silvia", "last_name"=>"Capra", "scopus_author_id"=>"55075671500"}, {"first_name"=>"Francesco", "last_name"=>"Vagni", "scopus_author_id"=>"55995707400"}, {"first_name"=>"Alessandro", "last_name"=>"Vercelli", "scopus_author_id"=>"7003369233"}, {"first_name"=>"Giorgio", "last_name"=>"Battaglia", "scopus_author_id"=>"35510566700"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"372094700", "doi"=>"10.1371/journal.pone.0082654", "sgr"=>"84891931388", "scopus"=>"2-s2.0-84891931388", "isbn"=>"1932-6203", "pmid"=>"24324819"}, "id"=>"1a3e22cf-dd2d-307a-9a94-2244506615ad", "abstract"=>"Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients.", "link"=>"http://www.mendeley.com/research/selective-vulnerability-spinal-cortical-motor-neuron-subpopulations-delta7-sma-mice", "reader_count"=>22, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>11, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>11, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>8, "Neuroscience"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1306360"], "description"=>"<p>Coronal sections from cervical spinal cord (<b>A</b>) and brain (<b>C</b>) of WT (left) and SMA mice (right) stained with Neurotrace (red) and GFAP-immunoreacted (green). Note glial activation in the spinal cord and cortical layer V at P13 (bottom right in A and C) but not at P4. (<b>B</b>, <b>D</b>) Quantification of fluorescence intensity (expressed in arbitrary units, AU) revealed a significantly increased glial activation in both ventral (VH) and dorsal horns (DH) of the spinal cord (<b>B</b>) and in cortical layer V but not layers II-III (D) of SMA mice at P13 (<sup>***</sup>p<0.001, t-test). Values are expressed as mean ± SEM. Scale bar: 100 µm.</p>", "links"=>[], "tags"=>["activation", "sma"], "article_id"=>870688, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g007", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Glial_activation_in_916_7_SMA_mice_/870688", "title"=>"Glial activation in Δ7 SMA mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306355"], "description"=>"<p>(<b>A</b>) Representative ChAT reacted coronal sections of the cervical spinal cord illustrating Ax9 medial motor neurons (hatched lines) innervating axial muscles in WT (left) and SMA (right) at P13. Note the smaller neuronal size in SMA vs WT mice. (<b>B</b>, <b>D</b>) The average cross-sectional area was significantly reduced in SMA mice at both P4 (<b>B</b>) and P13 (<b>D</b>) stages (P4: 280 ± 8 µm<sup>2</sup> in SMA <i>vs</i> 371 ±10.5 µm<sup>2</sup> in WT, <sup>**</sup>p < 0.01, t-test; P13: 258 ± 7 µm<sup>2</sup> in SMA <i>vs</i> 392 ± 14 µm<sup>2</sup> in WT, <sup>***</sup>p < 0.001). (<b>C</b>, <b>E</b>) The distribution of MN cross-sectional areas at both P4 (<b>C</b>) and P13 (<b>E</b>) showed a significant shift to lower size in SMA <i>vs</i> WT mice (<sup>***</sup>p<0.001, chi-square test between WT and SMA curves). Values are expressed as mean ± SEM. Scale bar: 100 µm. </p>", "links"=>[], "tags"=>["axial"], "article_id"=>870683, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selective_loss_of_axial_motor_neurons_/870683", "title"=>"Selective loss of axial motor neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306342"], "description"=>"<p>(<b>A</b>) Low-power images of ChAT immunoreacted spinal cord sections at ventral C3-C5 cervical levels from WT (upper) and SMA (lower) mice at pre- (P4, left) and late-symptomatic (P13, right) disease stages. Note that the C5 area of ChAT<sup>+</sup> immunoreactivity was smaller in SMA than in WT mice at both P4 and P13. (<b>B</b>) Stereological analysis revealed that total motor neuron number was reduced at P4 (left) and significantly decreased at P13 (right) in SMA compared to WT mice (<sup>*</sup>p<0.05, t-test). (<b>C</b>) Western-blot analysis revealed increased ChAT expression between P4 and P13 in WT mice. Values are expressed as mean ± SEM. Scale bar: 100 µm.</p>", "links"=>[], "tags"=>[], "article_id"=>870677, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stereological_analysis_of_ChAT_motor_neurons_/870677", "title"=>"Stereological analysis of ChAT<sup>+</sup> motor neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306357"], "description"=>"<p>(<b>A</b>) Photographs of P4 and P13 mouse brains showing a clear reduction of brain size in SMA <i>vs</i> WT mice at P13 (right). No difference in size were observed at P4 (left). (<b>B</b>) Quantitative analysis of brain weight in SMA <i>vs</i> WT littermates at P4 and P13. A weight reduction of about 30% was observed at late-symptomatic (P13: <sup>***</sup>p<0.001, t-test) but not at pre-symptomatic (P4) stages. (<b>C</b>) Nissl-stained brain sections illustrating reduced numbers of larger pyramidal neurons (red asterisks in the inset) in layer V of SMA mice <i>vs</i> WT controls. (<b>D</b>) Stereological counts of Nissl-stained brain sections revealing a significant 52% decrease (<sup>**</sup>p<0.01, t-test) of pyramidal neuron density in layer V of P9 SMA <i>vs</i> WT mice. The density of pyramidal neurons was already reduced at P4, without reaching statistical significance (p>0.05). Values are expressed as mean ± SEM. Scale bars: 5 mm in A; 50 µm in C.</p>", "links"=>[], "tags"=>["pyramidal", "neurons"], "article_id"=>870685, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g006", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loss_of_layer_V_pyramidal_neurons_of_motor_cortex_/870685", "title"=>"Loss of layer V pyramidal neurons of motor cortex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306353"], "description"=>"<div><p>(<b>A</b>) Representative ChAT reacted coronal sections of the cervical spinal cord illustrating 3 different motor neuron (MN) pools (hatched lines) in WT at P13: phrenic MNs at C3 level (a1), lateral MNs at C5-C6 innervating forelimb proximal muscles (a2), and lateral MNs at C8 innervating forelimb distal muscles (a3). </p>\n\t\t\t\t\t\t<p>(<b>B</b>) Quantitative analysis of mean areas of the 3 MN pools in SMA <i>vs</i> WT mice revealed a significant soma size reduction only in the MN pool innervating proximal forelimb muscles (left, P4: 386.3 ± 22.5 µm<sup>2</sup> in SMA <i>vs</i> 526.5 ±15 µm<sup>2</sup> in WT, <sup>**</sup>p < 0.01, t-test; right, P13: 378 ± 13 µm<sup>2</sup> in SMA <i>vs</i> 599.7 ± 20.7 µm<sup>2</sup> in WT, <sup>***</sup>p < 0.001). Mean area were unchanged in phrenic MNs (left) and not significantly reduced in MNs innervating distal muscles (right). (<b>C</b>) The analysis of soma size distribution of MNs innervating proximal muscles revealed a significant shift to lower size in SMA <i>vs</i> WT mice at P4 (left) and even more at P13 (right) (<sup>***</sup>p<0.001, chi-square test between WT and SMA curves). Values are expressed as mean ± SEM. Scale bar: 100 µm.</p></div>", "links"=>[], "tags"=>["proximal"], "article_id"=>870681, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selective_loss_of_proximal_motor_neurons_/870681", "title"=>"Selective loss of proximal motor neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306344"], "description"=>"<p>(<b>A</b>) Quantitative analysis at C3-C5 spinal levels revealed a significant reduction of mean motor neuron area in SMA <i>vs</i> WT mice at P4 (left) and P13 (right, <sup>***</sup>p<0.001, t-test). (<b>B</b>, <b>C</b>) The analysis of the distribution of motor neuron areas (bins=100 µm<sup>2</sup>) revealed a significant shift to lower size in SMA <i>vs</i> WT mice at both P4 and P13 (<sup>***</sup>p<0.001, chi-square test between WT and SMA curves). Also note the reduction of motor neurons larger than 500 µm<sup>2</sup> in SMA mice. Values are expressed as mean ± SEM.</p>", "links"=>[], "tags"=>["neurons", "selectively", "affected"], "article_id"=>870679, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Large_motor_neurons_are_selectively_affected_in_SMA_/870679", "title"=>"Large motor neurons are selectively affected in SMA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306343"], "description"=>"<p>(<b>A</b>) Representative Nissl-stained coronal sections of ventral C5 spinal cord from WT (left) and SMA (right) mice at prenatal (E19, upper), pre- (P4, middle) and late-symptomatic (P13, lower) disease stages. (<b>B</b>) No difference in the total cervical motor neuron number was evident at prenatal stages (E19, left), whereas a progressive reduction was evident post-natally (P4, middle), reaching statistical significance at late-symptomatic stages (P13, right: <sup>*</sup>p<0.05, t-test). Values are expressed as mean ± SEM. Scale bar: 100 µm.</p>", "links"=>[], "tags"=>["nissl-stained"], "article_id"=>870678, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0082654.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stereological_analysis_of_Nissl_stained_motor_neurons_/870678", "title"=>"Stereological analysis of Nissl-stained motor neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-06 02:57:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1306361", "https://ndownloader.figshare.com/files/1306362"], "description"=>"<div><p>Loss of the survival motor neuron gene (<i>SMN1</i>) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients.</p> </div>", "links"=>[], "tags"=>["vulnerability", "spinal", "cortical", "neuron", "subpopulations", "delta7", "sma"], "article_id"=>870689, "categories"=>["Biological Sciences"], "users"=>["Paolo d’Errico", "Marina Boido", "Antonio Piras", "Valeria Valsecchi", "Elena De Amicis", "Denise Locatelli", "Silvia Capra", "Francesco Vagni", "Alessandro Vercelli", "Giorgio Battaglia"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0082654.s001", "https://dx.doi.org/10.1371/journal.pone.0082654.s002"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selective_Vulnerability_of_Spinal_and_Cortical_Motor_Neuron_Subpopulations_in_delta7_SMA_Mice_/870689", "title"=>"Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-12-06 02:57:31"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
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  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"19", "full-text"=>"29", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"21", "full-text"=>"19", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"15", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Physical sciences/Mathematics", "average_usage"=>[259, 431, 541, 639, 727, 816, 898, 980, 1061, 1136, 1214, 1294, 1356]}]}
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