A Method for Studying the Effects of Neurochemicals on Long-Term Compensation in Unilaterally Labyrinthectomized Rats

A new method has been developed to study the influence of drugs and toxicants on longterm recovery of dynamics in the horizontal vestibulo-ocular reflex of the rat after hemilabyrinthectomy (HL). HL was performed by injecting sodium arsanilate into the middle ear. The lesion was confirmed by histology. Eye movements elicited by sinusoidal vestibular stimulation, in both light and darkness, were recorded by a search-coil technique and then analyzed by a computer program created with virtual instrument soft-ware, which calculated the gain of the slow-phase velocity (SPV) and the saccades para-meters (frequency, amplitude, and peak velocity) to the lesioned side and to the intact side separately. During the 2-10 week period after HL, repeated analysis of the spontaneous long-term recovery of such parameters revealed a slight but significant reduction of the post-HL asymmetry between SPV gain to the lesioned side and to the intact side. During the follow-up period, a post-HL increase of the phase lead remained unchanged. The reduced number of saccades/min was not completely restored. To test the usefulness of the experimental model for neurochemical investigation of such adaptation, we administered baclofen and toluene to rats 8–12 wk after hemilabyrinthectomy. Baclofen, a specific GABAB agonist, immediately restored the symmetry of SPV gain. By contrast, toluene, which has some effects on the central vestibular system that are related to GABAB transmission, aggravated the asymmetry in both the SPV gain and the number of saccades. We suggest that the experimental model would be useful for studying neurochemical mechanisms in vestibular adaptation processes

Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig

Aim: To investigate the therapeutic potential for treating inner ear damage of two new steroidal alkaloid compounds, Dendrogenin A and Dendrogenin B, previously shown to be potent inductors of cell differentiation. Methods: Guinea pigs, unilaterally deafened by neomycin infusion, received a cochlear implant followed by immediate or a two-week delayed treatment with Dendrogenin A, Dendrogenin B, and, as comparison artificial perilymph and glial cell-line derived neurotrophic factor. After a 4-week treatment period the animals were sacrificed and the cochleae processed for morphological analysis. Electrically-evoked auditory brainstem responses were measured weekly throughout the experiment. Results: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors. Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group. Conclusions: Our results suggest that Dendrogenins constitute a new class of drugs with strong potential to improve cochlear implant efficacy and to treat neuropathy/synaptopathy related hearing loss. That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number

Влияние параметров торцовой фрезы на характер обработанной поверхности

Материалы ХI Международной науч.-техн. конф. студентов, магистрантов и аспирантов [28-29 апреля 2011 г., г. Гомель]. - Гомель, 2011

Single molecule analysis of combinatorial splicing

Alternative splicing creates diverse mRNA isoforms from single genes and thereby enhances complexity of transcript structure and of gene function. We describe a method called spliceotyping, which translates combinatorial mRNA splicing patterns along transcripts into a library of binary strings of nucleic acid tags that encode the exon composition of individual mRNA molecules. The exon inclusion pattern of each analyzed transcript is thus represented as binary data, and the abundance of different splice variants is registered by counts of individual molecules. The technique is illustrated in a model experiment by analyzing the splicing patterns of the adenovirus early 1A gene and the beta actin reference transcript. The method permits many genes to be analyzed in parallel and it will be valuable for elucidating the complex effects of combinatorial splicing

Inactivation of Pmel Alters Melanosome Shape But Has Only a Subtle Effect on Visible Pigmentation

PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit in later stages. PMEL is well conserved among vertebrates, and allelic variants in several species are associated with reduced levels of eumelanin in epidermal tissues. However, in most of these cases it is not clear whether the allelic variants reflect gain-of-function or loss-of-function, and no complete PMEL loss-of-function has been reported in a mammal. Here, we have created a mouse line in which the Pmel gene has been inactivated (Pmel−/−). These mice are fully viable, fertile, and display no obvious developmental defects. Melanosomes within Pmel−/− melanocytes are spherical in contrast to the oblong shape present in wild-type animals. This feature was documented in primary cultures of skin-derived melanocytes as well as in retinal pigment epithelium cells and in uveal melanocytes. Inactivation of Pmel has only a mild effect on the coat color phenotype in four different genetic backgrounds, with the clearest effect in mice also carrying the brown/Tyrp1 mutation. This phenotype, which is similar to that observed with the spontaneous silver mutation in mice, strongly suggests that other previously described alleles in vertebrates with more striking effects on pigmentation are dominant-negative mutations. Despite a mild effect on visible pigmentation, inactivation of Pmel led to a substantial reduction in eumelanin content in hair, which demonstrates that PMEL has a critical role for maintaining efficient epidermal pigmentation

Mercury (Hg2+) suppression of potassium currents of outer hair cells

Article discussing mercury (Hg2+) suppression of potassium currents of outer hair cells