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.
Highlights
The basal forebrain (BF) is an ensemble of distinct subcortical nuclei containing several cell types that are heterogeneous with respect to transmitter content, neuronal morphology and efferent outputs collectively projecting to multiple brain areas, such as the cortical mantle, hippocampus and olfactory bulb [1]
A clear activation profile presenting an age-dependent reduction in peak activity and a lower response could be distinguished throughout developmental stages
(G4), whereas during early developmental stages and in Alzheimer’s disease (AD), it is found primarily as a monomer. This pathological reversal back to a monomer has been attributed to an inability to oligomerize(G1). This pathological reversal to a monomer has beenpeptide, attributed to anhas inability to oligomerize to the absence of disulfide bondsback containing the C-terminal which been cleaved to play due tointhe absence of disulfide bonds containing theinC-terminal peptide, which has been cleaved to a role degeneration, as it would have previously development: the dominance of G1 in play a role in degeneration, as it would have previously in development: the dominance of G1 in development and AD is most importantly indicative of the cleaved T14 peptide, the key bioactive molecule in development and degeneration [12,36]
Summary
The basal forebrain (BF) is an ensemble of distinct subcortical nuclei containing several cell types that are heterogeneous with respect to transmitter content, neuronal morphology and efferent outputs collectively projecting to multiple brain areas, such as the cortical mantle, hippocampus and olfactory bulb [1] This telencephalic complex has long been implicated in cortical activation, attention, motivation, memory and, most importantly, in neurodegenerative diseases [2]. AChE can exert a non-hydrolytic function, independent of cholinergic transmission [6,7], and is present in all vulnerable neurons prone to neurodegeneration [8], irrespective of their particular transmitter system.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
