Biology subjects

Mashouri, P.

Publications and source records attributed to Mashouri, P..

4 recordsLinked to original sources

bioRxiv2023

The Effect of Gradual Ovarian Failure on Dynamic Muscle Function and the Role of High Intensity Interval Training on Mitigating Impairments

Skeletal muscle function is impaired in menopause and exercise may mitigate tshis decline. We used the VCD model of menopause to investigate the effects of gradual ovarian failure on skeletal muscle contractile function and whether high intensity interval training (HIIT) can mitigate impairments. Sexually mature female CD-1 mice were assigned to one of three groups: control (n=5), VCD-sedentary (n=5), or VCD-training (n=5). Following ovarian failure, the VCD-training group underwent 8 weeks of uphill HIIT. Mice were sacrificed 8 weeks after ovarian failure, representing late menopause. Single muscle fibres from the soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected, chemically permeabilized, and mechanically tested. Single muscle fibres were maximally activated (pCa 4.5) then isotonic load clamps were performed to calculate force-velocity-power curves. Absolute force and peak power were 31% and 32% lower in VCD-sedentary fibres compared to control fibres, respectively, in both SOL and EDL muscles. Despite reductions in absolute force and therefore lighter relative loads imposed during the isotonic contractions in VCD-sedentary fibres, there were no concomitant increases in contractile velocity. HIIT was partially effective at mitigating power loss (22% higher peak power in VCD-training compared to VCD-sedentary), but only in fast-type SOL fibres. These findings indicate that ovarian failure impairs dynamic contractile function - likely through a combination of lower force-generating capacity and slower shortening velocity - and that HIIT may be insufficient to completely counteract the deleterious effects of menopause at the cellular level. New & NoteworthyO_LIReductions in circulating ovarian hormones impair static muscle contractile performance, but less is known about dynamic properties like power. C_LIO_LITypically, rodent models of menopause completely remove the ovaries and fail to mimic the prolonged and complex hormonal transition that includes a retention in ovarian androgen production. C_LIO_LIUsing an ovary intact VCD model of ovarian failure, we found that single fibre power was impaired compared with controls in both SOL and EDL fibres. C_LIO_LIOur uphill high intensity interval training program was partially sufficient to reverse power loss, but only in fast-type SOL fibres. C_LIO_LIImpairments in muscle power following ovarian failure are likely driven by a combination of decreased muscle size and force-generating capacity. C_LI

physiology↗

bioRxiv2023

Effects of VCD-induced ovarian failure on single muscle fiber contractility in a mouse model of menopause

ObjectiveMenopause is associated with impairments in muscle contractile function. The temporal and mechanistic basis of this dysfunction are not known. Using a mouse model of menopause we identified how gradual ovarian failure affects single muscle fiber contractility. Study designMice were injected with VCD over 15 days and ovarian failure developed over 120 days. Mice were then sacrificed and slow-type soleus (SOL) and fast-type extensor digitorum longus (EDL) muscles were dissected and chemically permeabilized for mechanical testing. Main outcome measuresMuscle fiber contractility was assessed via: force, rate of force redevelopment, instantaneous stiffness, and calcium sensitivity across three relative force levels (pCa10,pCa50,pCa90). ResultsPeak force and cross-sectional area (CSA) of the SOL were [~]33% and [~]24% greater in the VCD group as compared with controls (P<0.05), respectively, with no differences in force produced by the EDL fibers across groups (P>0.05). Upon normalizing force to CSA there were no differences across groups (P>0.05). Rate of force development was [~]33% faster for SOL in the VCD group compared to control. Ca2+ sensitivity did not differ between groups for either muscle at pCa50 (P>0.05). In the VCD group, Ca2+ sensitivity was higher for EDL, but lower for SOL at pCa10 and pCa90 (P<0.05), respectively. ConclusionsIn our mouse model of menopause, alterations to muscle contractility were much less evident as compared with ovariectomized models. This divergence across models highlights the importance of better approximating the natural trajectory of menopause during and after the transitional phase of ovarian failure on neuromuscular function.

physiology↗

bioRxiv2022

An increase in serial sarcomere number induced via weighted downhill running improves work loop performance in the rat soleus

Increased serial sarcomere number (SSN) has been observed in rats via downhill running training due to the emphasis on active lengthening contractions; however, little is known about the influence on dynamic contractile function. Therefore, we employed 4 weeks of weighted downhill running training in rats, then assessed soleus SSN and work loop performance. We hypothesized trained rats would produce greater net work output during faster, higher-strain work loops due to a greater SSN. Thirty-one Sprague-Dawley rats were assigned to a control or training group. Weight was added during downhill running via a custom-made vest, progressing from 5-15% body mass. Following sacrifice, the soleus was dissected, and a force-length relationship was constructed. Work loops (active shortening followed by passive lengthening) were then performed about optimal muscle length (LO) at 1.5-3-Hz cycle frequencies and 1-7-mm strains to assess net work output. Muscles were then fixed in formalin at LO. Fascicle lengths and sarcomere lengths were measured and used to calculate SSN. Intramuscular collagen content and crosslinking were quantified via a hydroxyproline content and pepsin-solubility assay. Trained rats had longer fascicle lengths (+13%), greater SSN (+8%), greater specific active forces (+50%), and lower passive forces (-45-62%) than controls (P<0.05). There were no differences in collagen parameters (P>0.05). Net work output was greater (+101-424%) in trained than control rats for the 1.5-Hz loops at 1, 3, and 5-mm strains (P<0.05) and showed relationships with fascicle length (R2=0.14-0.24, P<0.05). These results suggest training-induced longitudinal muscle growth may improve dynamic performance.

physiology↗

bioRxiv2020

The influence of training-induced sarcomerogenesis on the history dependence of force

The increase or decrease in isometric force following active muscle lengthening or shortening, relative to a reference isometric contraction at the same muscle length and level of activation, are referred to as residual force enhancement (rFE) and residual force depression (rFD), respectively. The purpose of these experiments was to gain further mechanistic insight into the trainability of rFE and rFD, on the basis of serial sarcomere number (SSN) alterations to length-dependent properties. Maximal rFE/rFD measures from the soleus and extensor digitorum longus (EDL) of rats were compared after 4 weeks of uphill/downhill running and a no running control. Serial sarcomere numbers adapted to the training: soleus serial sarcomere number was greater with downhill compared to uphill running, while EDL demonstrated a trend towards more serial sarcomeres for downhill compared to no running. In contrast, absolute and normalized rFE/rFD did not differ across training groups for either muscle. As such, it appears that training-induced SSN adaptations do not modify rFE/rFD at the whole-muscle level. Summary StatementThe addition and subtraction of serial sarcomeres induced by downhill and uphill running, respectively, did not influence the magnitude of stretch-induced force enhancement and shortening-induced force depression.

physiology↗