TY - JOUR
T1 - A multidisciplinary approach reveals an age-dependent expression of a novel bioactive peptide, already involved in neurodegeneration, in the postnatal rat forebrain
AU - Ferrati, Giovanni
AU - Brai, Emanuele
AU - Stuart, Skye
AU - Marino, Celia
AU - Greenfield, Susan A.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - AChE-derived peptide
KW - Alzheimer’s disease
KW - Basal forebrain
KW - Development
KW - Nicotinic receptors
KW - Optical imaging
UR - http://www.scopus.com/inward/record.url?scp=85050953604&partnerID=8YFLogxK
U2 - 10.3390/brainsci8070132
DO - 10.3390/brainsci8070132
M3 - Article (Academic Journal)
C2 - 29996490
AN - SCOPUS:85050953604
SN - 2076-3425
VL - 8
JO - Brain Sciences
JF - Brain Sciences
IS - 7
M1 - 132
ER -