Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneous eye movements were recorded before and after a microinjection (0.1-0.2 microliter) of either APV (an NMDA receptor antagonist) or NBQX (a non-NMDA receptor antagonist) into the nucleus prepositus hypoglossi (NPH) of the alert cat. A unilateral injection of APV caused bilateral failure of the horizontal gaze-holding system: in the light, each saccade was followed by a post-saccadic drift. A unilateral injection of NBQX caused no sign of gaze-holding failure; in the light, spontaneous eye movements were unaffected; in complete darkness, a nystagmus with linear slow phases directed towards the injected side was observed. We conclude that NMDA receptors of the NPH neurones are involved in the gaze-holding system.
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PMID:NMDA receptors are involved in temporal integration in the oculomotor system of the cat. 791 92

The involvement of NMDA (N-methyl-D-aspartic acid) receptors in the initial stage of the vestibular compensation was evaluated by examining the effect of MK-801 on this compensation in guinea pigs. MK-801, injected 30 min before induction of unilateral labyrinthectomy by an arsanilate, significantly (P < 0.05) reduced the maximum frequency of the spontaneous nystagmus (SN) towards both the arsanilate-applied and the intact sides. In addition, injection of arsanilate into the opposite middle ear, 60 days subsequent to induction of the unilateral labyrinthectomy, suppressed the SN towards the second injected side, but had no effect on the SN towards the first injected side. These results suggest that NMDA receptors may be linked to the initiation of the vestibular compensation.
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PMID:Evidence for the involvement of NMDA receptors in vestibular compensation. 883 26

The frog horizontal monocular optokinetic nystagmus (H-OKN) is asymmetrical, the reflex being evoked by a temporal-nasal (T-N) component, but not by a nasal-temporal (N-T) component. Coil recordings showed that, in adult animals, 8 days of monocular deprivation (by unilateral eyelid suture) provoked the appearance of a N-T component, the H-OKN becoming symmetrical, reacting for both directions of stimulation. This delay was shortened to 2 days following two successive unilateral pretectal administrations of NMDA or of LY 285 265, an NMDA agonist, the first 2 days of eyelid suture. The same results were obtained when chronic microinjections of NMDA or LY 285 265 were achieved, the frogs being maintained in total darkness during the week of eyelid suture. These data indicate that the plasticity phenomenon evidenced in the monocular frog H-OKN depends on the activation of the NMDA receptors of one pretectum. This activation was obtained either by a monocular light stimulation of 8 days duration, or by unilateral administration of drugs activating the NMDA glutamatergic pretectal system. In this last case, the light stimulation was no longer necessary.
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PMID:Involvement of NMDA in a plasticity phenomenon observed in the adult frog monocular optokinetic nystagmus. 920 12

N-Methyl-D-aspartate receptor subunit 1-like immunoreactivity (NMDAR1-LI) was investigated in the brain of Rana pipiens during optic nerve regeneration. Following unilateral optic-nerve crush, frogs were tested for prey-catching and optokinetic nystagmus responses to assess return of visual function. At 1, 2, 3 and 5 months after the surgery, NMDAR1-LI was assessed in central visual pathways. At 3 and 5 months, conspicuous ipsilateral NMDAR1-LI fibers were detected in the thalamic and pretectal nuclei, and the time of their appearance coincided with the onset of behavioral recovery. Also, only ipsilateral retinorecipient layers in the optic tectum showed increased NMDAR1-LI during optic nerve regeneration. These results suggest that NMDA receptors may be present on retinal ganglion cell axons and terminals that have been misrouted during regeneration.
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PMID:NMDAR1-like immunoreactive fibers appear in the ipsilateral optic tract during optic nerve regeneration in Rana pipiens. 940 37

Advances made in understanding the pathophysiology of eye movement disorders have only recently with the publication of the first well-planned studies been translated into better treatment strategies. The following chapter summarizes the pharmacological treatment options for a variety of oculomotor syndromes. Cortisone is useful, for example, for acute vestibular neuritis to improve the restitution of the labyrinthine function. For the widespread benign paroxysmal positioning nystagmus, a series of liberating movements that free the semicircular canal from the causative otoconia is now a well-established therapy. Treatment for the central vestibular syndrome of up- and downbeat nystagmus consists of drugs like the potassium canal blocker 4-aminopyridine, which influence the cerebellar circuits involved in the disorder's pathophysiology. Acquired pendular nystagmus, one of the oculomotor syndromes often caused by multiple sclerosis, results in the severe impairment of reduced visual acuity. Memantine, a weak NMDA antagonist, has now been proven effective here. Finally, anticonvulsants like carbamazepine are the drugs of choice for disorders involving a nerve-blood vessel contact that induces symptoms of vestibular paroxysmia or superior oblique myokymia.
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PMID:Therapeutic considerations for eye movement disorders. 1731 84

For the development of rabbit models of Systemic Lupus Erythematosus (SLE), immunoglobulin allotype-defined pedigreed rabbits from the National Institute of Allergy and Infectious Diseases rabbit resource more closely approximate human populations due to their non-inbred pedigreed structure. In an initial study from this laboratory, peptides (SM and GR) from the spliceosomal Smith (Sm) and the NMDA glutamate receptor NR2b, on branched polylysine backbones (BB) elicited antinuclear and anti-dsDNA autoantibodies typical of SLE, as well as seizures and nystagmus sometimes observed as neurological manifestations in SLE patients. This suggested the feasibility of further selective breeding to develop a more reproducible rabbit model for investigations of SLE. Here we report the results of GR-MAP-8 and control BB immunization on autoantibody responses in a group of 24 rabbits specifically bred and developed from parents and ancestors tested for autoantibody responses. The changes in hematological profile and blood chemistry in the experimental rabbits were evaluated along with autoantibody responses. Elevations of total white blood cell (WBC), monocyte, eosinophil and basophil counts that developed following immunizations were moderately influenced by litter and presence of the antibody heavy chain allotype VH1a1. Autoantibody development followed a sequential pattern with anti-nuclear antibodies (ANA) followed by anti-dsDNA and subsequently anti-Sm and anti-RNP similar to SLE patients. High autoantibody levels to one autoantigen were not always associated with antibody response to another. Female rabbits had higher prevalence and levels of autoantibodies similar to human SLE. Higher autoantibody levels of anti-dsDNA and -ANA were observed among some full sibs and the presence of high responder ancestors in the pedigree was associated the augmented responses. We observed significant association between highest antibody responses to GR-MAP-8 and highest anti-dsDNA levels. Naturally occurring autoantibodies were found in some pre-immune sera and some unique ANA fluorescent staining patterns within the experimental group were observed. Background immunofluorescence in pre-immune sera, distinct patterns of programmed autoantibody responses unique among individual rabbits may have been modulated by genetic constitution, gender and environmental factors including exposure to antigens. The high incidence and intensity of autoantibody responses among descendants of high responders suggest that there may be an additive mode of inheritance with high heritability. It is conceivable that further rigorous pedigree selection for autoantibody responses could lead to development of rabbit models with spontaneous occurrence of SLE like serology and disease phenotypes.
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PMID:Genetic contributions to the autoantibody profile in a rabbit model of Systemic Lupus Erythematosus (SLE). 1860 65

Marfanoid habitus (MH) combined with intellectual disability (ID) is a genetically and clinically heterogeneous group of overlapping disorders. We performed exome sequencing in 33 trios and 31 single probands to identify novel genes specific to MH-ID. After the search for variants in known disease-causing genes and non-disease-causing genes with classical approaches, we searched for variants in non-disease-causing genes whose pLI was above 0.9 (ExAC Consortium data), in which truncating variants were found in at least 3 unrelated patients. Only DLG4 gene met these criteria. Data from the literature and various databases also indicated its implication in ID. DLG4 encodes post-synaptic density protein 95 (PSD-95), a protein expressed in various tissues, including the brain. In neurons, PSD-95 is located at the post-synaptic density, and is associated with glutamatergic receptor signaling (NMDA and AMPA). PSD-95 probably participates in dendritogenesis. Two patients were heterozygous for de novo frameshift variants and one patient carried a a consensus splice site variant. Gene expression studies supported their pathogenicity through haploinsufficiency and loss-of-function. Patients exhibited mild-to-moderate ID, similar marfanoid features, including a long face, high-arched palate, long and thin fingers, pectus excavatum, scoliosis and ophthalmological manifestations (nystagmus or strabismus). Our study emphasizes the role of DLG4 as a novel post-synaptic-associated gene involved in syndromic ID associated with MH.
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PMID:Truncating variants of the DLG4 gene are responsible for intellectual disability with marfanoid features. 2946 Apr 36