RESUMO
Amacrine interneurons, which are highly diversified in morphological, neurochemical, and physiological features, play crucial roles in visual information processing in the retina. However, the specification mechanisms and functions in vision for each amacrine subtype are not well understood. We found that the Prdm13 transcriptional regulator is specifically expressed in developing and mature amacrine cells in the mouse retina. Most Prdm13-positive amacrine cells are Calbindin- and Calretinin-positive GABAergic or glycinergic neurons. Absence of Prdm13 significantly reduces GABAergic and glycinergic amacrines, resulting in a specific defect of the S2/S3 border neurite bundle in the inner plexiform layer. Forced expression of Prdm13 distinctively induces GABAergic and glycinergic amacrine cells but not cholinergic amacrine cells, whereas Ptf1a, an upstream transcriptional regulator of Prdm13, induces all of these subtypes. Moreover, Prdm13-deficient mice showed abnormally elevated spatial, temporal, and contrast sensitivities in vision. Together, these results show that Prdm13 regulates development of a subset of amacrine cells, which newly defines an amacrine subtype to negatively modulate visual sensitivities. Our current study provides new insights into mechanisms of the diversification of amacrine cells and their function in vision.
Assuntos
Células Amácrinas/metabolismo , Neurônios Colinérgicos/metabolismo , Sensibilidades de Contraste , Histona-Lisina N-Metiltransferase/metabolismo , Interneurônios/metabolismo , Fatores de Transcrição/metabolismo , Células Amácrinas/citologia , Células Amácrinas/fisiologia , Animais , Neurônios Colinérgicos/citologia , Neurônios Colinérgicos/fisiologia , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Histona-Lisina N-Metiltransferase/genética , Interneurônios/citologia , Interneurônios/fisiologia , Camundongos , Neurogênese , Fatores de Transcrição/genéticaRESUMO
Surgical treatment of osteoporotic vertebral collapse (OVC) with neurological deficits presents significant clinical challenges because some patients have fragile bones and often have medical comorbidities, which affect the severity of osteoporosis. We hypothesized that clinical results of surgery in these patients depend on the extent of medical comorbidities that induce secondary osteoporosis. The aim of this study is to examine the effects of medical history and comorbidities on surgical outcomes for these patients, along with the factors that predict postoperative function in activities of daily living (ADL). We retrospectively reviewed data for 88 patients with OVC and neurological deficits who underwent surgery. We assessed clinical results regarding neurological deficits and function in ADL. The presence or absence of comorbidities responsible for secondary osteoporosis and treatments or medical events that affect bone metabolism were examined. We performed statistical analysis to examine prognostic factors for postoperative function in ADL. Of 88 patients, the distributions of comorbidities, treatment, and events in medical history were as follows: hypertension, 57 patients (64.8%); chronic kidney disease (CKD) stage 3 or 4, 32 (36.4%); diabetes mellitus, 16 (18.2%); liver dysfunction, 11 (12.5%); cardiovascular disease, 10 (11.4%); rheumatoid arthritis, 9 (10.2%); and glucocorticoid intake, 8 (9.1%). Twenty-five patients (28.4%) represented poor postoperative ADL (chair-bound or bed-bound), and 11 of 25 patients with poor postoperative ADL represented full neurological recovery. Multivariate analysis revealed decreased estimated glomerular filtration rate (odds ratio 0.96; 95% confidence interval 0.93-0.99; p = 0.005) and a high serum alkaline phosphatase (ALP) level (odds ratio 1.01; 95% CI 1.00-1.02; p = 0.01) were strong predictive factors for poor postoperative function in ADL. The majority of patients with poor postoperative function in ADL had advanced CKD with a disorder of bone metabolism as well as bone fragility.
Assuntos
Atividades Cotidianas , Doenças do Sistema Nervoso/complicações , Osteoporose/complicações , Fraturas da Coluna Vertebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Dieta , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças do Sistema Nervoso/fisiopatologia , Razão de Chances , Osteoporose/fisiopatologia , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/fisiopatologia , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/psicologiaRESUMO
INTRODUCTION: Investigation of preoperative manifestations of thoracic myelopathy in a large population has not been reported. The aim of this study was to identify symptoms specific to anatomical pathology or compressed segments in thoracic myelopathy through investigation of preoperative manifestations. MATERIALS AND METHODS: Subjects were 205 patients [143 men, 62 women; mean age, 62.2 (range 21-87 years)] with thoracic myelopathy who underwent surgery at our affiliate institutions from 2000 to 2011. The disease distribution included ossification of the ligamentum flavum (OLF) in 106 patients, ossification of the posterior longitudinal ligament (OPLL) in 17, OLF with OPLL in 17, intervertebral disc herniation (IDH) in 23, OLF with IDH in 3, and spondylosis in 39. We assessed (1) initial and preoperative complaints, (2) neurological findings, (3) Japanese Orthopaedic Association scores (JOA, full score, 11 points), (4) the compressed segments, and (5) preoperative duration. Multivariate analyses were performed to examine potential relationships between preoperative manifestations and anatomical pathology or compressed segments. RESULTS: The multivariate analyses revealed relationships between lower limb muscle weakness and T10/11 anterior compression; lower limb pain and T11/12 anterior compression; low back pain and T11/12 compression; and hyporeflexia in the patellar tendon reflex/foot drop and T12/L1 anterior compression. CONCLUSION: This study elucidated symptoms specific to anatomical pathology or compressed segments in thoracic myelopathy. These relationships can be helpful in the initial investigation of thoracic diseases, although additional measures such as MRI or CT are necessary for definitive diagnosis.
Assuntos
Doenças Neuromusculares/etiologia , Doenças da Medula Espinal/complicações , Vértebras Torácicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Compressão da Medula Espinal/complicações , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
In vertebrate retinal development, various transcription factors are known to execute essential activities in gene regulation. Although epigenetic modification is considered to play a pivotal role in retinal development, the exact in vivo role of epigenetic regulation is still poorly understood. We observed that G9a histone methyltransferase, which methylates histone H3 at lysine 9 (H3K9), is substantially expressed in the mouse retina throughout development. To address in vivo G9a function in the mouse retina, we ablated G9a in retinal progenitor cells by conditional gene knock-out (G9a Dkk3 CKO). The G9a Dkk3 CKO retina exhibited severe morphological defects, including photoreceptor rosette formation, a partial loss of the outer nuclear layer, elevated cell death, and persistent cell proliferation. Progenitor cell-related genes, including several cyclins, Hes1, Chx10, and Lhx2, are methylated on histone H3K9 in the wild-type retina, but they were defective in H3K9 methylation and improperly upregulated at late developmental stages in the G9a Dkk3 CKO retina. Notably, conditional depletion of G9a in postmitotic photoreceptor precursors (G9a Crx CKO) led to the development of an almost normal retina, indicating that G9a activity mainly in retinal progenitor cells, but not in photoreceptor precursors, is essential for normal terminal differentiation of and survival of the retina. Our results suggest that proper epigenetic marks in progenitor cells are important for subsequent appropriate terminal differentiation and survival of retinal cells by repressing progenitor cell-related genes in differentiating retinal cells.
Assuntos
Morte Celular/fisiologia , Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Histona-Lisina N-Metiltransferase/fisiologia , Retina/crescimento & desenvolvimento , Células-Tronco/enzimologia , Animais , Morte Celular/genética , Diferenciação Celular/genética , Epigênese Genética/genética , Epigênese Genética/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Histona-Lisina N-Metiltransferase/genética , Metilação , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Retina/anatomia & histologia , Retina/enzimologia , Células-Tronco/fisiologiaRESUMO
PURPOSE: In general, osteoporotic vertebral collapse (OVC) with neurological deficits requires sufficient decompression of neural tissues to restore function level in activities of daily living (ADL). However, it remains unclear as to which procedure provides better neurological recovery. The primary purpose of this study was to compare neurological recovery among three typical procedures for OVC with neurological deficits. Secondary purpose was to compare postoperative ADL function. METHODS: We retrospectively reviewed data for 88 patients (29 men and 59 women) with OVC and neurological deficits who underwent surgery. Three typical kinds of surgical procedures with different decompression methods were used: (1) anterior direct neural decompression and reconstruction (AR group: 27 patients), (2) posterior spinal shorting osteotomy with direct neural decompression (PS group: 36 patients), and (3) posterior indirect neural decompression and short-segment spinal fusion combined with vertebroplasty (VP group: 25 patients). We examined clinical results regarding neurological deficits and function level in ADL and radiological results. RESULTS: The mean improvement rates for neurological deficits and ADL function level were 60.1 and 55.0%, respectively. There were no significant differences among three groups in improvement rates for neurological deficits or ADL function level. The VP group had a significantly lower estimated mean blood loss (338 mL) and mean duration of surgery (229 min) than both the AR and PS groups (p < 0.001). CONCLUSION: Direct neural decompression is not always necessary, and the majority of patients can be treated with a less-invasive procedure such as short-segment posterior spinal fusion with indirect decompression combined with vertebroplasty. The high-priority issue is careful evaluation of patients' general health and osteoporosis severity, so that the surgeon can choose the procedure best suited for each patient.