A splice variant of the TATA-box binding protein encoding the polyglutamine-containing N-terminal domain that accumulates in Alzheimer's disease.

Previously we have reported the accumulation of an N-terminal fragment of the TATA-box binding protein (TBP) in Alzheimer's disease brain tissue and here we report the identification of a naturally occurring TBP splice variant as a likely mechanism for its production. The splice variant described here encodes the polyglutamine-containing N-terminal domain of this key transcription factor. We demonstrate the expression of the splice variant mRNA in a variety of human tissues and that the resulting protein forms inclusions in cell culture transfection studies.

P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea.

Type I and type II spiral ganglion neurons (SGN) innervate the inner and outer hair cells of the cochlea, respectively. This neural system is established by reorganization of promiscuous innervation of the hair cells, immediately before hearing is established. The mechanism for this synaptic reorganization is unresolved but probably includes regulation of trophic support between the hair cells and the neurons.

TRPC-like conductance mediates restoration of intracellular Ca2+ in cochlear outer hair cells in the guinea pig and rat.

Ca2+ signalling is central to cochlear sensory hair cell physiology through its influence on sound transduction, membrane filter properties and neurotransmission. However, the mechanism for establishing Ca2+ homeostasis in these cells remains unresolved. Canonical transient receptor potential (TRPC) Ca2+ entry channels provide an important pathway for maintaining intracellular Ca2+ levels.

Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea.

ATP-gated ion channels assembled from P2X3 receptor (P2X3R) subunits contribute to neurotransmission and neurotrophic signaling, associated with neurite development and synaptogenesis, particularly in peripheral sensory neurons. Here, P2X3R expression was characterized in the rat cochlea from embryonic day 16 (E16) to adult (P49-56), using RT-PCR and immunohistochemistry. P2X3R mRNA was strongly expressed in the cochlea prior to birth, declined to a minimal level at P14, and was absent in adult tissue.

Activation of purinergic receptor subtypes modulates odor sensitivity.

Purinergic nucleotides, including ATP and adenosine, are important neuromodulators of peripheral auditory and visual sensory systems (Thorne and Housley, 1996). ATP released by the olfactory epithelium (OE) after noxious stimuli provides a physiological source for a neuromodulatory substance independent of efferent innervation. Here we show that multiple subtypes of purinergic receptors are differentially expressed in olfactory receptor neurons and sustentacular support cells.

Allosteric modulation of native cochlear P2X receptors: insights from comparison with recombinant P2X2 receptors.

Extracellular adenosine 5'-triphosphate (ATP)-gated ion channels assembled from P2X receptor subunits exhibit subunit-selective allosteric modulation by protons and divalent cations. In voltage-clamped guinea-pig cochlear outer hair cells (OHC) and Deiters' cells (DC), H(+) and Cu(2+), but not Zn(2+), enhanced the P2X receptor-mediated inward currents. Acid pH (6.

Potential role of purinergic signalling in cochlear pathology.

Adenosine triphosphate (ATP) is a major intercellular signalling molecule that is involved in neurotransmission in the central and autonomic nervous systems, regulation of blood flow, and neuroendocrine function. It is also a key signalling molecule involved in normal cochlear homoeostasis, regulating hearing sensitivity, controlling vascular tone and acting as a candidate neurotransmitter at the hair cell afferent synapses. It has also been established that extracellular ATP mediates some pathological processes such as inflammation, apoptosis and cell proliferation.