Wheel Running Improves Motor Function and Spinal Cord Plasticity in Mice With Genetic Absence of the Corticospinal Tract

Abstract

Our previous studies showed that mutant mice with congenital absence of the corticospinal tract (CST) undergo spontaneous remodeling of motor networks to partially compensate for absent CST function. Here, we asked whether voluntary wheel running could further improve locomotor plasticity in CST-deficient mice. Adult mutant mice were randomly allocated to a “runners” group with free access to a wheel, or a “non-runners” group with no access to a wheel. In comparison with non-runners, there was a significant motor improvement including fine movement, grip strength, decreased footslip errors in runners after 8-week training, which was supported by the elevated amplitude of electromyography recording and increased neuromuscular junctions in the biceps. In runners, terminal ramifications of monoaminergic and rubrospinal descending axons were significantly increased in spinal segments after 12 weeks of exercise compared to non-runners. 5-ethynyl-2′-deoxyuridine (EDU) labeling showed that proliferating cells, 90% of which were Olig2-positive oligodendrocyte progenitors, were 4.8-fold more abundant in runners than in non-runners. In 8-week runners, RNAseq analysis of spinal samples identified 404 genes up-regulated and 398 genes down-regulated, and 69 differently expressed genes involved in signal transduction, among which the NF-κB, PI3K-Akt and cyclic AMP (cAMP) signaling were three top pathways. Twelve-week training induced a significant elevation of postsynaptic density protein 95 (PSD95), synaptophysin 38 and myelin basic protein (MBP), but not of brain derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and insulin like growth factor-1 (IGF-1). Thus, locomotor training activates multiple signaling pathways, contributes to neural plasticity and functional improvement, and might palliate locomotor deficits in patients.

Voluntary exercise training improves body weight of leptin-deficient ob/ob mice by altering hepatic stearoyl-CoA desaturase 1 and deleted in breast cancer 1 protein levels

“…Exercise training has many metabolic benefits, including plasma lipoprotein and triglyceride (TG) levels [ 18 ], and glycemic control [ 19 ]. Voluntary aerobic exercise prevents ageand high-fat-induced vascular dysfunction, mitochondrial oxidative stress, and inflammation in mice [ 20 ], and improves motor function and spinal cord plasticity [ 21 ]. These benefits could be preserved in those who exercise throughout their lives.…”

Inhibition of the TLR4/NF-κB/TNF-α axis by TAK-242 or PDTC reduces central nervous system inflammation to alleviate lipopolysaccharide induced sickness behaviors in mice

“…No. 12183018A, Invitrogen Life Technologies) for whole-genome gene expression analysis according to the previous reports [20]. Brie y, the quality and quantity of the puri ed RNA were assessed using Agilent 2100 Bioanalyzer.The method based on fragments per kilobase of exon per million fragments mapped (FPKM) was used to calculate gene expression.…”

“…The brain was collected into postxed in 4% PFA for 24h and dehydrated with 15% sucrose at 4℃overnight, followed by 30% sucrose at 4℃for 24h. For immuno uorescence, a standard protocol was used with minor modi cations [20]. Brie y, 20µm frozen coronal sections were washed with PBS three times, permeabilized (PBS with 1.5% Triton X-100), blocked (PBS with 10% goat serum plus 3% bovine serum albumin) and incubated with primary antibodies overnight at 4℃.…”

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) and Treadmill Training on Recovery of Motor Function in a Rat Model of Partial Spinal Cord Injury

“…Exercise training aimed at promoting motor function has been studied extensively with SCI patients and animal models [ 9 ]. The biological effects of exercise training mainly include preventing dendritic atrophy of motor neurons [ 10 ], inducing collateral sprouting of axons [ 11 ], reducing myelin loss [ 12 ], and promoting the expressions of neurotrophic factors [ 13 ]. Some studies reported that exercise training is beneficial to improve motor function after SCI [ 14 – 16 ].…”