Immunohistochemical distribution of calcium binding proteins in the cochlear nuclear complex of circling mice / Distribución inmunohistoquímica de proteínas de unión a calcio en el complejo nuclear coclear de ratones circulantes

SUMMARY: The term "circling mouse" refers to an animal model of deafness, in which the mouse exhibits circling, head tossing, and hyperactivity, with pathological features including degenerated spiral ganglion cells in the cochlea, and the loss of the organ of Corti. The cochlear nuclear (CN) complex, a part of the auditory brain circuit, is essential to process both ascending and descending auditory information. Considering calcium's (Ca2+) importance in homeostasis of numerous biological processes, hearing loss by cochlear damage, either by ablation or genetic defect, could cause changes in the Ca2+ concentration that might trigger functional and structural alterations in the auditory circuit. However, little is known about the correlation of the central nervous system (CNS) pathology in circling mice, especially of the auditory pathway circuit and Ca2+ changes. This present study investigates the distribution of Ca2+- binding proteins (CaBPs), calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR) by using a free floating immunohistochemical method inthe CN of the wild-type mouse (+/+), the heterozygous mouse (+/cir), and the homozygous (cir/cir) mouse. CaBPs are well known to be an important factor that regulates Ca2+ concentrations. Compared with the dorsal and ventral cochlear nuclei of +/+ and +/ cirmice, prominent decreases of CaBPs' immunoreactivity (IR) in cir/cirmice were observed in the somas, as well as in the neuropil. The present study reportson the overall distribution and changes in the immunoreactivity of CaBPs in the CN of cir/cirmice because ofa hearing defect. This data might be helpful to morphologically elucidate CNS disorders and their relation to CaBPs immunoreactivity related to hearing defects.

RESUMEN: El término "ratón circulante" se refiere a un modelo animal con sordera, en el que el ratón exhibe hiperactividad, movimientos circulares y movimientos de la cabeza, con características patológicas que incluyen células ganglionares espirales degeneradas en la cóclea, un canal de Rosenthal vacío y la pérdida del órgano de Corti. El complejo nuclear coclear (CN), una parte del circuito cerebral auditivo, es esencial para procesar la información auditiva tanto ascendente como descendente. Considerando la importancia del calcio (Ca2+) en la homeostasis de numerosos procesos biológicos, la hipoacusia por daño coclear, por ablación o por defecto genético, podría provocar cambios en la concentración de Ca2+que pueden desencadenar alteraciones funcionales y estructurales en el circuitoauditivo. Sin embargo, existe poca información de la correlación de la patología del sistema nervioso central (SNC) en ratones circulantes, especialmente del circuito de la víaauditiva y los cambios de Ca2+. Este estudio nvestiga la distribución de proteínas de unión a Ca2+ (CaBP), calbindina D-28k (CB), parvalbúmina (PV) y calretinina (CR) mediante el uso de un método inmunohistoquímico de flotaciónlibre en el CN del ratón de tiposalvaje (+/+), el ratón heterocigoto (+/cir) y el ratón homocigoto (cir/cir). Se sabe que los CaBP son un factor importante que regula las concentraciones de Ca2+. En comparación con los núcleos cocleares dorsal y ventral de los ratones +/+ y +/ cir, se observaron disminuciones prominentes de la inmunorreactividad (IR) de CaBPs en los ratonescir/cir en los somas, asícomo en el neuropilo. El presente estudio informa sobre la distribución general y los cambios en la inmunorreactividad de CaBP en el CN de ratones cir/cir debido a un defecto auditivo. Estos datos podrían ser útiles para dilucidar morfológicamente los trastornos del SNC y su relación con la inmunorreactividad de CaBP relacionada con los defectosauditivos.

Immunohistochemical Localization of Glycine Receptor (alpha1+alpha2) in the Auditory Brain Stem of Circling Mouse / 대한해부학회지

Hearing loss in adults can stem from damage to the cochlea and the cochlear nerves inflicted by intense noise, mechanical trauma, or disease. Hearing loss is associated with degenerative changes in central auditory pathways, and hearing deficits are often accompanied by changes in the synaptic organization of the central auditory pathways. In addition to structural rearrangements, hearing loss may induce changes in the strength of synaptic transmissions. These effects may alter both transient and persistent regulation of transmitter release from glutamatergic, glycinergic, and GABAergic pathways in the auditory brain stem. The converging excitatory and inhibitory inputs are exquisitely organized topographically and are aligned perfectly with each other. The LSO and MNTB in the mammalian auditory brain stem provide and receive many glycinergic inputs. Thus, this auditory system is a useful model to study inhibitory synaptic development. However, little is known about the inhibitory synapses in the central nervous system. First, we used immunohistochemistry to compare the glycine receptor (GlyR) distribution in the LSO and MNTB, which project glycinergic inhibitory input into the auditory brainstem, in circling mice (P16), which have a spontaneous mutation in the inner ear, with wild-type mice. The relative immunoreactive density of the LSO was 86.4+/-7.2 in wild-type, 76.7+/-10.7 in heterozygous, and 61.1+/-4.1 in homozygous mice. The relative immunoreactive density of the MNTB was 97.6+/-8.7 in wild-type, 91.7+/-8.9 in heterozygous, and 74.9+/-7.8 in homozygous mice. These results reveal a decreased GlyR immunoreactivity in both the LSO and MNTB, which may be attributable to a postsynaptic decrease in GlyR number. Our model uses congenitally deaf mice, in which both spontaneous and evoked auditory nerve activity are disrupted because of dysfunctional hair cell-spiral ganglion cell transmission. This provides a naturally occurring model that may provide valuable insights into the central aspects of human congenital deafness in addition to the central consequences of a lack of auditory nerve activity. Our results are likely to be relevant to our understanding of the central changes underlying human hereditary deafness.