TY - JOUR
T1 - Treadmill exercise intervention improves gait and postural control in alpha-synuclein mouse models without inducing cerebral autophagy
AU - Minakaki, Georgia
AU - Canneva, Fabio
AU - Chevessier, Frédéric
AU - Bode, Frederik
AU - Menges, Stefanie
AU - Timotius, Ivanna K.
AU - Kalinichenko, Liubov S.
AU - Meixner, Holger
AU - Müller, Christian P.
AU - Eskofier, Bjoern M.
AU - Casadei, Nicolas
AU - Riess, Olaf
AU - Schröder, Rolf
AU - Winkler, Jürgen
AU - Xiang, Wei
AU - von Hörsten, Stephan
AU - Klucken, Jochen
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/5/2
Y1 - 2019/5/2
N2 - Gait and postural control dysfunction are prototypical symptoms compromising quality of life for patients with Parkinson's disease (PD). Hallmarks of cellular pathology are dopaminergic degeneration and accumulation of the cytosolic protein alpha-synuclein, linked to impaired autophagy-lysosome pathway (ALP) clearance. Physical exercise improves gait in PD patients and motor function in rodent lesion models. Moreover, exercise is considered neuroprotective and ALP induction has been reported, e.g. in human skeletal muscle, rodent peripheral and cerebral tissues. A combined analysis of how distinct exercise paradigms affect motor and central biochemical aspects of PD could maximize benefits for patients. Here we examine the effect of 4 weeks treadmill exercise intervention in 7–8 month non-lesioned mice on a) distinct gait categories, b) ALP activity, c) dopaminergic and alpha-synuclein homeostasis. The study includes wild type, alpha-synuclein knockout, and mice exclusively expressing human alpha-synuclein. Parameters of gait regularity and stability, activity, and dynamic postural control during unforced walk, were assessed by an automated system (CatWalk XT). At baseline, alpha-synuclein mouse models exhibited irregular and less active gait, with impaired dynamic postural control, compared to wild type mice. Treadmill exercise particularly improved speed and stride length, while increasing dual diagonal versus three-paw body support in both the alpha-synuclein knockout and transgenic mice. Biochemical analyses showed higher striatal tyrosine hydroxylase immuno-reactivity and reduced higher-order alpha-synuclein species in the cerebral cortex. However, no significant cerebral ALP induction was measured. In summary, treadmill exercise improved gait activity and postural stability, and promoted dopaminergic and alpha-synuclein homeostasis, without robustly inducing cerebral ALP.
AB - Gait and postural control dysfunction are prototypical symptoms compromising quality of life for patients with Parkinson's disease (PD). Hallmarks of cellular pathology are dopaminergic degeneration and accumulation of the cytosolic protein alpha-synuclein, linked to impaired autophagy-lysosome pathway (ALP) clearance. Physical exercise improves gait in PD patients and motor function in rodent lesion models. Moreover, exercise is considered neuroprotective and ALP induction has been reported, e.g. in human skeletal muscle, rodent peripheral and cerebral tissues. A combined analysis of how distinct exercise paradigms affect motor and central biochemical aspects of PD could maximize benefits for patients. Here we examine the effect of 4 weeks treadmill exercise intervention in 7–8 month non-lesioned mice on a) distinct gait categories, b) ALP activity, c) dopaminergic and alpha-synuclein homeostasis. The study includes wild type, alpha-synuclein knockout, and mice exclusively expressing human alpha-synuclein. Parameters of gait regularity and stability, activity, and dynamic postural control during unforced walk, were assessed by an automated system (CatWalk XT). At baseline, alpha-synuclein mouse models exhibited irregular and less active gait, with impaired dynamic postural control, compared to wild type mice. Treadmill exercise particularly improved speed and stride length, while increasing dual diagonal versus three-paw body support in both the alpha-synuclein knockout and transgenic mice. Biochemical analyses showed higher striatal tyrosine hydroxylase immuno-reactivity and reduced higher-order alpha-synuclein species in the cerebral cortex. However, no significant cerebral ALP induction was measured. In summary, treadmill exercise improved gait activity and postural stability, and promoted dopaminergic and alpha-synuclein homeostasis, without robustly inducing cerebral ALP.
KW - Alpha-synuclein
KW - Autophagy
KW - Instrumented gait analysis
KW - Mouse gait pattern
KW - Parkinson's disease
KW - Treadmill exercise
UR - http://www.scopus.com/inward/record.url?scp=85061370683&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2018.11.035
DO - 10.1016/j.bbr.2018.11.035
M3 - Article
C2 - 30599154
AN - SCOPUS:85061370683
SN - 0166-4328
VL - 363
SP - 199
EP - 215
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -