A Multidisciplinary Approach Reveals an Age-Dependent Expression of a Novel Bioactive Peptide, Already Involved in Neurodegeneration, in the Postnatal Rat Forebrain

Abstract

The basal forebrain has received much attention due to its involvement in multiple cognitive functions, but little is known about the basic neuronal mechanisms underlying its development, nor those mediating its primary role in Alzheimer’s disease. We have previously suggested that a novel 14-mer peptide, ‘T14’, could play a pivotal role in Alzheimer’s disease, via reactivation of a developmental signaling pathway. In this study, we have characterized T14 in the context of post-natal rat brain development, using a combination of different techniques. Ex-vivo rat brain slices containing the basal forebrain, at different stages of development, were used to investigate large-scale neuronal network activity in real time with voltage-sensitive dye imaging. Subsequent Western blot analysis revealed the expression profile of endogenous T14, its target alpha7 nicotinic receptor and the familiar markers of Alzheimer’s: amyloid beta and phosphorylated Tau. Results indicated maximal neuronal activity at the earliest ages during development, reflected in a concomitant profile of T14 peptide levels and related proteins. In conclusion, these findings show that the peptide, already implicated in neurodegenerative events, has an age-dependent expression, suggesting a possible contribution to the physiological mechanisms underlying brain maturation.

Keywords

• development
• basal forebrain
• AChE-derived peptide
• nicotinic receptors
• optical imaging
• Alzheimer’s disease