Abstract
Memory impairments in Alzheimer’s disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.
Highlights
Alzheimer’s disease is a progressive, degenerative, and irreversible neurological disorder
There was a significant increase in the preference index in the vehicle-administered WT mice during the test session (P = 0.011, d = 2.00), whereas there was no increase in the vehicle-administered 5XFAD mice (P = 0.26, d = 0.58)
The administration of a low dose (12 mg kg−1 day−1) of the Polygalae Radix (PR) extract showed a tendency to increase the preference index in the test session (P = 0.080, d = 1.31). These results demonstrated that the PR extract prevented impairment of object recognition memory in the 5XFAD mice
Summary
Alzheimer’s disease is a progressive, degenerative, and irreversible neurological disorder. AD can develop due to heterogeneous risk factors, such as genome, epigenome, and environments (Killin et al, 2016; Maloney and Lahiri, 2016; Pimenova et al, 2017), the common features of AD include amyloid β (Aβ)-induced degeneration of neurites, disruption of neural networks, and memory deficits (Dickson and Vickers, 2001; Hardy and Selkoe, 2002; Perl, 2010; Selkoe and Hardy, 2016). Preventing axonal degeneration could inhibit the progression of memory deficits in AD (Dickson and Vickers, 2001; Hardy and Selkoe, 2002; Simmons et al, 2014). Axonal regeneration is related to recovery from cognitive dysfunction in murine models of AD (Tohda, 2016)
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.
