Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice.
Nerve growth factor (NGF) delivery to the brain of patients appears to be an emerging potential therapeutic approach to neurodegenerative disease, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracere-broventricular infusion and gene therapy. We previously showed that intranasal administration of NGF determined an amelioration of cholinergic deficit and a decrease in the number of phosphotau-positive neurons and of beta-amyloid accumulation in AD11 mice, which express transgenic antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like neurodegeneration. In this study, we report that the Alzheimer-like neurodegeneration in AD11 mice is linked to progressive behavioral deficits in visual recognition memory and spatial memory starting from 4 months of age. To establish whether intranasal administration of NGF, started after the appearance of the first memory deficits, could revert the cognitive deficits in AD11 mice, we assessed the performance of NGF-treated or control AD11 mice in the object recognition test and in a test of memory for place and context. Deficits exhibited by untreated AD11 mice could be rescued by the intranasal administration of NGF. Thus, this route of administration provides a promising way to deliver NGF to the brain in a therapeutic perspective.
De Rosa
Roberta
R
Lay Line Genomics S.p.A., Via di Castel Romano 100, 00128 Rome, Italy.
Garcia
Addys Ancheta
AA
Braschi
Chiara
C
Capsoni
Simona
S
Maffei
Lamberto
L
Berardi
Nicoletta
N
Cattaneo
Antonino
A
D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000008:administration & dosage*
D020932:Nerve Growth Factor
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