Phosphorylated cAMP response element-binding protein levels in guinea pig brainstem auditory nuclei after unilateral cochlear ablation.

After left unilateral cochlear ablation (UCA) in young adult guinea pigs, the appearance of plasticities in auditory pathways suggested altered gene expression and modified phenotypic behaviors of auditory neurons. Because phosphorylated cyclic-AMP response element-binding protein (CREB-P) is a transcription factor that binds to certain genes to facilitate their expression, CREB-P levels were measured after UCA and correlated with postablation plasticities. After UCA, Western blotting was employed to quantify CREB-P levels and illustrate CREB levels in the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) cochlear nucleus; the lateral (LSO) and medial superior olive (MSO); the medial nucleus of the trapezoid body (MNTB); and the central nucleus of the inferior colliculus (ICc) for up to 145 days. We also quantified the levels of several protein synthesis regulators and synaptic markers in the AVCN at 60 days. Sucrose-based extraction buffer improved CREB-P recovery. CREB-P levels became depressed at 3 and 7 postablation days, except in the PVCN, where they were elevated at 7 days, and in the ICc, where they were elevated at both times. At 60 days, CREB-P levels in all the nuclei were elevated. In the AVCN, levels of the protein synthesis regulators and synaptic markers were also elevated at 60 days. By 145 days, CREB-P levels again declined, except in the AVCN, where elevations persisted and increased on the ablated side, and in the ICc, where CREB-P elevations remained. The changes in CREB-P levels coincided with several plasticities in glutamatergic and glycinergic transmitter release and receptor activities, and alterations in neurotrophic support, that developed after UCA. These findings suggest that UCA altered CREB-P levels, which in turn might have contributed to plasticities that appear after UCA.

Pubmed ID: 16511870 RIS Download