Lack of Tff3 Peptide Results in Hearing Impairment and Accelerated Presbyacusis

Abstract

Tff peptides are secreted mainly by the gastrointestinal epithelial cells and their primary role is maintaining normal structure and function of mucous epithelia. Ongoing studies on their expression pattern have disclosed other sites of their synthesis thus revealing additional physiological functions in the organism. Here we present new data about Tff3 expression in the cochlea of the rodent inner ear. On the basis of RT-PCR we describe the presence of Tff3 transcripts in both, a mouse cDNA library isolated from whole cochleae from postnatal days 3-15 (P3-P15), and also in cochlear tissue. By using a riboprobe for the fragment containing exon 1, 2 and 3 of Tff3, in situ hybridization, localized Tff3 signals in neurons of spiral ganglion and vestibular organ. We did not observe any abnormalities in the middle ear of Tff3 knock-out mice, neither did histological examination of the inner ear indicate any gross morphological changes in the cochlea. However, ABR (auditory evoked brain stem responses) audiograms revealed that the Tff3 knock-out animals show an accelerated presbyacusis and a hearing loss of about 15 dB at low frequencies increasing to 25 dB loss at higher frequencies. These findings suggest that Tff3 could play a role in neurosensory signaling. Further studies are needed to clarify this new function in the auditory system.

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

“…Expression of Tff3 in the organ of Corti, including in hair cells and supporting cells has been described previously [10,18]. However, our previous preliminary study revealed no gross morphological abnormalities in the cochlea of Tff3 mutant animals [10].…”

“…Expression of Tff3 in the organ of Corti, including in hair cells and supporting cells has been described previously [10,18]. However, our previous preliminary study revealed no gross morphological abnormalities in the cochlea of Tff3 mutant animals [10]. Therefore we now performed a detailed study in adult wildtype and Tff3 deficient mice and surveyed the distribution of a series of key proteins related with auditory function.…”

“…We showed that Tff3 knock-out mice display a deterioration of hearing with age, a feature characteristic for presbyacusis (age related hearing loss) [11,12]. However, in Tff3 deficient animals we did not observe any degeneration of cochlear hair cells and spiral ganglion neurons or atrophy of the stria vascularis (SV) [10].…”

PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3

“…), and permanent guide cannulas (23-gauge; Plastics One, Roanoke, VA, USA) were implanted bilaterally 1 mm above the BLA. The coordinates (Lubka et al, 2008;Wang et al, 2008) for the BLA were the following: anterior/ posterior, À2.9 mm; medial/lateral, ± 5.0 mm; dorsal/ventral, À8.5 mm (Kessler et al, 2003). The cannulas were anchored to the skull with stainless-steel screws and dental cement.…”

“…Previous studies suggested that TFF3 influences the development of the CNS. Lack of TFF3 resulted in hearing impairment and accelerated presbyacusis (Lubka et al, 2008). However, some reports found no obvious neural abnormalities in transgenic TFF3 knockout mice (Mashimo et al, 1996).…”