-
Autonomic Neuroscience : Basic &... Mar 2020Sexual dysfunction, following spinal cord injury (SCI), is highly dependent on the extent of injury. SCI disrupts the supraspinal innervation of the reproductive organs;...
Sexual dysfunction, following spinal cord injury (SCI), is highly dependent on the extent of injury. SCI disrupts the supraspinal innervation of the reproductive organs; resulting in structural and functional deficits. Relating the extent of SCI to these changes could eventually improve diagnoses and treatment planning of sexual dysfunction following SCI. In the present study, following chronic SCI of different severities (1/3 dorsal SCI (1/3 SCI), 2/3 dorsal SCI (2/3 SCI), and complete transection (Tx)) at T8 spinal level, histological changes of seminiferous tubules parameters in testis were examined. The diameter of seminiferous tubules (DST) and epithelial height of seminiferous tubules (HST) were significantly decreased in all SCI groups compared to control and sham. In addition, DST in 2/3 SCI and Tx groups and HST in Tx group were significantly decreased in comparison with 1/3 SCI animals. Nonetheless, the diameter of seminiferous tubules' lumen decreased significantly in 2/3 SCI and Tx compared to control, sham, and 1/3 SCI groups. Concerning cellular component, the number of spermatocytes and spermatids layers significantly decreased in both 1/3 and 2/3 SCI in comparison to normal. However, Tx had the most prominent deteriorating effect on these layers; indicating impairment in the process of spermatogenesis. These results show that the spinal tracts are part of the neural circuitries innervating the testis and responsible for their structural support. These tracts are mainly distributed between the lateral and ventral funiculi at T8 spinal level. Consequently, sparing ventral funiculi in the SCI prevents the severe decline in spermatogenesis.
Topics: Animals; Follicle Stimulating Hormone; Male; Organ Size; Rats, Sprague-Dawley; Spermatogenesis; Spinal Cord; Spinal Cord Injuries; Testis; Testosterone
PubMed: 31981803
DOI: 10.1016/j.autneu.2020.102639 -
Journal of Neurodevelopmental Disorders Dec 2019Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function....
BACKGROUND
Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function. Although altered neural development and function have been well described in people with DS, few studies have investigated the etiology underlying the observed motor phenotypes. Here, we examine the development, patterning, and organization of the spinal cord throughout life in the Ts65Dn mouse, a model that recapitulates many of the motor changes observed in people with DS.
METHODS
Spinal cords from embryonic to adult animals were processed for gene and protein expression (immunofluorescence) to track the spatiotemporal development of excitatory and inhibitory neurons and oligodendroglia. Postnatal analyses were focused on the lumbar region due to the reflex and gait abnormalities found in Ts65Dn mice and locomotive alterations seen in people with DS.
RESULTS
Between embryonic days E10.5 and E14.5, we found a larger motor neuron progenitor domain in Ts65Dn animals containing more OLIG2-expressing progenitor cells. These disturbed progenitors are delayed in motor neuron production but eventually generate a large number of ISL1+ migrating motor neurons. We found that higher numbers of PAX6+ and NKX2.2+ interneurons (INs) are also produced during this time frame. In the adult lumbar spinal cord, we found an increased level of Hb9 and a decreased level of Irx3 gene expression in trisomic animals. This was accompanied by an increase in Calretinin+ INs, but no changes in other neuronal populations. In aged Ts65Dn animals, both Calbindin+ and ChAT+ neurons were decreased compared to euploid controls. Additionally, in the dorsal corticospinal white matter tract, there were significantly fewer CC1+ mature OLs in 30- and 60-day old trisomic animals and this normalized to euploid levels at 10-11 months. In contrast, the mature OL population was increased in the lateral funiculus, an ascending white matter tract carrying sensory information. In 30-day old animals, we also found a decrease in the number of nodes of Ranvier in both tracts. This decrease normalized both in 60-day old and aged animals.
CONCLUSIONS
We show marked changes in both spinal white matter and neuronal composition that change regionally over the life span. In the embryonic Ts65Dn spinal cord, we observe alterations in motor neuron production and migration. In the adult spinal cord, we observe changes in oligodendrocyte maturation and motor neuron loss, the latter of which has also been observed in human spinal cord tissue samples. This work uncovers multiple cellular perturbations during Ts65Dn development and aging, many of which may underlie the motor deficits found in DS.
Topics: Animals; Disease Models, Animal; Down Syndrome; Female; Gene Expression Regulation, Developmental; Homeobox Protein Nkx-2.2; Homeodomain Proteins; Male; Mice, Transgenic; Neuroglia; Neurons; Nuclear Proteins; Spinal Cord; Transcription Factors; White Matter
PubMed: 31839007
DOI: 10.1186/s11689-019-9294-9 -
Molecular Neurobiology Feb 2020Neuroglial precursor cells (NPC) possess immune-modulatory properties by which they prevent immune-mediated injury in experimental autoimmune encephalomyelitis (EAE). It...
Neuroglial precursor cells (NPC) possess immune-modulatory properties by which they prevent immune-mediated injury in experimental autoimmune encephalomyelitis (EAE). It is unclear whether cell transplantation in a clinical-relevant setup induces ongoing therapeutic effects in a chronic-active model of progressive multiple sclerosis (MS). We examined whether human embryonic stem cell (hESC)-derived NPCs inhibit progressive EAE in Biozzi AB/H mice, manifesting with chronic-active neuroinflammation and demyelinated plaques. hESC-derived NPCs were propagated for 6-8 weeks as spheres enriched for Olig2+ cells to switch from neuronal to glial commitment and to enrich for oligodendrocyte progenitor cells. NPC were transplanted intracerebroventricularly at 30 days post-EAE induction, after the acute relapse. We evaluated effects of cell transplantation on clinical parameters, neuroinflammation, myelination, and axonal loss. Transplanted animals exhibited a significantly milder disease, reduced neuroinflammation, reduced demyelination, and reduced axonal loss as compared to control EAE mice. Toluidine-blue semi-thin staining showed a bystander neuroprotective effect of human precursor cells preventing the loss of myelinated fibers in superficial layer of the cervical dorsal funiculus. Human Olig2+ cells were detected along spinal cord meninges after 65 days of follow-up. In co-cultures in vitro, Olig2+ human precursors inhibited Concanavalin A-induced murine T cell activation and proliferation. To conclude, glial-committed human NPC induce ongoing immune-regulatory and neuroprotective effects, following transplantation into mice with a clinical-relevant model of chronic-active MS and during established disease, entering the chronic phase. These properties highlight the therapeutic potential of human NPC transplantation in chronic MS and their delivery via the cerebrospinal fluid.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Multiple Sclerosis; Myelin Sheath; Neural Stem Cells; Neurons; Oligodendrocyte Precursor Cells; Oligodendrocyte Transcription Factor 2; Stem Cell Transplantation
PubMed: 31656989
DOI: 10.1007/s12035-019-01802-7 -
Journal of Neurosurgery. Spine Oct 2019Dorsal spinal cord herniation is reportedly a rare condition. Here, the authors report an unusual case of dorsal spinal cord herniation at the thoracolumbar junction...
Dorsal spinal cord herniation is reportedly a rare condition. Here, the authors report an unusual case of dorsal spinal cord herniation at the thoracolumbar junction presenting with scalloping of ossification of the ligamentum flavum (OLF). A 75-year-old woman with a 2-year history of bilateral leg dysesthesia presented with progressive gait ataxia. Neurological examination showed bilateral patellar tendon hyperreflexia with loss of vibratory sensation and proprioception in her bilateral lower extremities. CT myelography revealed a posterior kink and dorsal herniation of the spinal cord at T11-12, with OLF between T10-11 and T12-L1. In addition, scalloping of the OLF was observed at T11-12 at the site of the herniated spinal cord. This scalloping was first noted 9 years previously and had been gradually progressing. The patient underwent surgical repair of the spinal cord herniation. Subsequently, her spinal cord herniation and vibratory sensation and proprioception in both legs partly improved, but gait ataxia remained unchanged. Dorsal spinal cord herniation reportedly occurs under conditions of vulnerability of the dorsal dura mater. In this case, acquired vulnerability of the dorsal dura mater owing to previous epidural catheter placement into the thoracolumbar space may have resulted in dorsal spinal cord herniation.
PubMed: 31628276
DOI: 10.3171/2019.8.SPINE19771