Phillip F. Gardiner

A Physical Activity Program Improves Behavior and Cognitive Functions in Children with ADHD: An Exploratory Study.

Objective: The objective of this study is to explore the effects of a moderate- to high-intensity physical activity program on fitness, cognitive functions, and ADHD-related behavior in children with ADHD. Method: Fitness level, motor skills, behaviors, and cognitive functions are assessed by standardized tests before and after a 10-week training or control period. Results: Findings show that participation in a physical activity program improves muscular capacities, motor skills, behavior reports by parents and teachers, and level of information processing. Conclusion: A structured physical activity program may have clinical relevance in the functional adaptation of children with ADHD. This supports the need for further research in the area of physical activity with this population.

Passive exercise and fetal spinal cord transplant both help to restore motoneuronal properties after spinal cord transection in rats

Spinal cord transection influences the properties of motoneurons and muscles below the lesion, but the effects of interventions that conserve muscle mass of the paralyzed limbs on these motoneuronal changes are unknown. We examined the electrophysiological properties of rat lumbar motoneurons following spinal cord transection, and the effects of two interventions shown previously to significantly attenuate the associated hindlimb muscle atrophy. Adult rats receiving a complete thoracic spinal cord transection (T‐10) were divided into three groups receiving: (1) no further treatment; (2) passive cycling exercise for 5 days/week; or (3) acute transplantation of fetal spinal cord tissue. Intracellular recording of motoneurons was carried out 4–5 weeks following transection. Transection led to a significant change in the rhythmic firing patterns of motoneurons in response to injected currents, as well as a decrease in the resting membrane potential and spike trigger level. Transplants of fetal tissue and cycling exercise each attenuated these changes, the latter having a stronger effect on maintenance of motoneuron properties, coinciding with the reported maintenance of structural and biochemical features of hindlimb muscles. The mechanisms by which these distinct treatments affect motoneuron properties remain to be uncovered, but these changes in motoneuron excitability are consistent with influences on ion conductances at or near the initial segment. The results may support a therapeutic role for passive limb manipulation and transplant of stem cells in slowing the deleterious responses of motoneurons to spinal cord injury, such that they remain more viable for subsequent alternative strategies. Muscle Nerve 29: 234–242, 2004

Community-based Exercise and Dietary Intervention During Pregnancy:A Pilot Study

ABSTRACT OBJECTIVE To determine the feasibility of implementing a communitybased exercise/dietary intervention program targeted at socioeconomically deprived pregnant women living in an urban core in an attempt to reduce risks of obesity and diabetes. METHODS Fifty-two participants were enrolled and randomized into additional intervention (AI) and standard care (SC) groups. Participants in the AI group undertook group and homebased exercises during pregnancy and received computerassisted Food Choice Map dietary interviews and counselling. Participants in the SC group received an information package on diet and activity for a healthy pregnancy. RESULTS Forty-five participants completed the study (SC group, n=21, AI group, n=24). No adverse effects of exercise were observed during the study. Physical activity levels in the AI group were greater than those in the SC group (p CONCLUSIONS The results of this pilot study demonstrated the feasibility of the lifestyle intervention during pregnancy and its potential to improve pregnancy outcomes in urban communities.

Contractile and electromyographic characteristics of rat plantaris motor unit types during fatigue in situ.

1. The ventral root dissection technique was used to obtain contractile and electromyogram (e.m.g.) characteristics of ninety‐five plantaris motor units in situ in pentobarbitone‐anaesthetized rats (n = 20). 2. Motor units demonstrated a wide spectrum of sizes, contractile speeds, and fatigue indices, and were categorized in the same manner as cat hind‐limb motor units. Fast‐fatigable (f.f.) and fast‐intermediate fatigue resistant (f.i.) motor units constituted 20.2 and 25.5% of the motor unit population but together generated over 75% of the cumulative tetanic force. Fast‐fatigue resistant (f.r.) and slow motor units composed 43.6 and 10.6% of the population while producing less than 25% of the aggregate tetanic force. 3. Only f.f. and a portion of f.i. motor units demonstrated extensive e.m.g. amplitude reductions during a standard fatigue test. Mean percentage e.m.g. decrease (from the first spike of the first burst to the last spike of the last burst) was 74.0 +/‐ 27.7% for f.f. units and 28.3 +/‐ 31.0% (mean +/‐ S.D.) for f.i. motor units. Relationships between percentage e.m.g. decline and motor unit size (tetanic force) showed significant (P less than 0.01) positive correlations in f.f. (r = 0.71) and f.i. (r = 0.69) motor units. 4. Backward extrapolation of the time course of the force‐e.m.g. relationship during the fatigue test revealed that declines in e.m.g. may explain 15, 21 and 66% of the force losses in f.r., f.i. and f.f. motor units. Slow motor units were fatigue resistant and demonstrated a mean e.m.g. decline of 4.3 +/‐ 6.2%. 5. Indirectly stimulated whole muscle was more fatigable than a composite constructed from motor unit data because of more severe e.m.g. amplitude reductions in the former. 6. The motor unit mechanical and electrical responses during the fatigue test do not summate linearly during whole muscle contractile activity. This is most likely due to the presence, during whole muscle activity, of metabolic changes during the fatigue regimen which influence neuromuscular propagation of excitation, which are not as severe during single motor unit activity.

Effects of daily spontaneous running on the electrophysiological properties of hindlimb motoneurones in rats

No evidence currently exists that motoneurone adaptations in electrophysiological properties can result from changes in the chronic level of neuromuscular activity. We examined, in anaesthetized (ketamine/xylazine) rats, the properties of motoneurones with axons in the tibial nerve, from rats performing daily spontaneous running exercise for 12 weeks in exercise wheels (‘runners’) and from rats confined to plastic cages (‘controls’). Motoneurones innervating the hindlimb via the tibial nerve were impaled with sharp glass microelectrodes, and the properties of resting membrane potential, spike threshold, rheobase, input resistance, and the amplitude and time‐course of the afterhyperpolarization (AHP) were measured. AHP half‐decay time was used to separate motoneurones into ‘fast’ (AHP half‐decay time < 20 ms) and ‘slow’ (AHP half‐decay time ≥ 20 ms), the proportions of which were not significantly different between controls (58 % fast) and runners (65 % fast). Two‐way ANOVA and ANCOVA revealed differences between motoneurones of runners and controls which were confined to the ‘slow’ motoneurones. Specifically, runners had slow motoneurones with more negative resting membrane potentials and spike thresholds, larger rheobasic spike amplitudes, and larger amplitude AHPs compared to slow motoneurones of controls. These adaptations were not evident in comparing fast motoneurones from runners and controls. This is the first demonstration that physiological modifications in neuromuscular activity can influence basic motoneurone biophysical properties. The results suggest that adaptations occur in the density, localization, and/or modulation of ionic membrane channels that control these properties. These changes might help offset the depolarization of spike threshold that occurs during rhythmic firing.

Endurance training alters the biophysical properties of hindlimb motoneurons in rats

The purpose of the study was to determine the effect of daily endurance treadmill training (2 h/day, 30 m/min) on motoneuron biophysical properties. Electrophysiological properties of tibial motoneurons were measured in situ in anesthetized (ketamine/xylazine) control and trained rats using sharp glass microelectrodes. Motoneurons from trained rats had significantly hyperpolarized resting membrane potentials and spike trigger levels, and faster antidromic spike rise‐times. “Fast” motoneurons (after‐hyperpolarization half‐decay time <20 ms) in trained rats also had a significantly larger mean cell capacitance than those in control rats, suggesting that they were larger, although this had no effect on indices of excitability (rheobase, cell input resistance). Motoneurons are thus targets for activity‐induced adaptations, which may have clinical significance for the role of physical activity as a therapeutic modality in cases of neurological deficit. The specific adaptations noted, which reflect alterations in ionic conductances, may serve to offset decreases in membrane excitability that occur during sustained excitation.

Muscle denervation promotes opening of the permeability transition pore and increases the expression of cyclophilin D.

Loss of neural input to skeletal muscle fibres induces atrophy and degeneration with evidence of mitochondria‐mediated cell death. However, the effect of denervation on the permeability transition pore (PTP), a mitochondrial protein complex implicated in cell death, is uncertain. In the present study, the impact of 21 days of denervation on the sensitivity of the PTP to Ca2+‐induced opening was studied in isolated muscle mitochondria. Muscle denervation increased the sensitivity to Ca2+‐induced opening of the PTP, as indicated by a significant decrease in calcium retention capacity (CRC: 111 ± 12 versus 475 ± 33 nmol (mg protein)−1 for denervated and sham, respectively). This phenomenon was partly attributable to in vivo mitochondrial and whole muscle Ca2+ overload. Cyclosporin A, which inhibits PTP opening by binding to cyclophilin D (CypD), was significantly more potent in mitochondria from denervated muscle and restored CRC to the level observed in mitochondria from sham‐operated muscles. In contrast, the CypD independent inhibitor trifluoperazine was equally effective at inhibiting PTP opening in sham and denervated animals and did not correct the difference in CRC between groups. This phenomenon was associated with a significant increase in the content of the PTP regulating protein CypD relative to several mitochondrial marker proteins. Together, these results indicate that Ca2+ overload in vivo and an altered expression of CypD could predispose mitochondria to permeability transition in denervated muscles.

Frequency–current relationships of rat hindlimb α‐motoneurones

The purpose of this study was to describe the frequency–current (f–I) relationships of hindlimb α‐motoneurones (MNs) in both anaesthetized and decerebrate rats in situ. Sprague–Dawley rats (250–350 g) were anaesthetized with ketamine and xylazine (KX) or subjected to a precollicular decerebration prior to recording electrophysiological properties from sciatic nerve MNs. Motoneurones from KX‐anaesthetized rats had a significantly (P < 0.01) hyperpolarized resting membrane potential and voltage threshold (Vth), increased rheobase current, and a trend (P= 0.06) for a smaller after‐hyperpolarization (AHP) amplitude compared to MNs from decerebrate rats. In response to 5 s ramp current injections, MNs could be categorized into four f–I relationship types: (1) linear; (2) adapting; (3) linear + sustained; and (4) late acceleration. Types 3 and 4 demonstrated self‐sustained firing owing to activation of persistent inward current (PIC). We estimated the PIC amplitude by subtracting the current at spike derecruitment from the current at spike recruitment. Neither estimated PIC nor f–I slopes differed between fast and slow MNs (slow MNs exhibited AHP half‐decay times > 20 ms) or between MNs from KX‐anaesthetized and decerebrate rats. Motoneurones from KX‐anaesthetized rats had significantly (P < 0.02) hyperpolarized ramp Vth values and smaller and shorter AHP amplitudes and decay times compared to MNs from decerebrate rats. Pentobarbitone decreased the estimated PIC amplitude and almost converted the f–I relationship from type 3 to type 1. In summary, MNs of animals subjected to KX anaesthesia required more current for spike initiation and rhythmic discharge but retained large PICs and self‐sustained firing. The KX‐anaesthestized preparation enables direct recording of PICs in MNs from intact animals.

Acetylcholinesterase Adaptation to Voluntary Wheel Running is Proportional to the Volume of Activity in Fast, but not Slow, Rat Hindlimb Muscles

Chronic enhancement of neuromuscular activity by forced exercise training programmes results in selective adaptation of the G4 acetylcholinesterase (AChE) molecular form in hindlimb fast muscles of the rat, with only minor and non‐selective AChE changes in the soleus. In order to shed further light on the physiological significance of this G4 adaptation to training, we turned to a voluntary exercise model. The impact of 5 days and 4 weeks of voluntary wheel cage running on AChE molecular forms was examined in four hindlimb fast muscles and the slow‐twitch soleus from two rat strains. Inbred Fisher and Sprague– Dawley rats, placed in live‐in wheel cages, exercised spontaneously for distances which progressively increased up to an average of ∼3 and 18 km/day, respectively, by the end of week 4. Fast muscles responded to this voluntary activity by massive G4 increases (up to 420%) with almost no changes in A12, so that by week 4 the tetramer became the main AChE component of these muscles. The additional G4 was composed primarily of amphiphilic molecules, suggesting a membrane‐bound state. The G4 content of fast muscles was highly correlated with the distance covered by the rats during the 5 days before they were killed (r= 0.850‐0.879, P < 0.001 in three muscles). The soleus muscle, in turn, responded to wheel cage activity by a marked selective reduction of its asymmetric forms—up to 45% for A12. This A12 decline, already maximal by day 5 of wheel cage running, showed no relationship with the distance covered. The present results constitute strong new evidence suggesting that the role of AChE in neuromuscular transmission is not limited solely to the rapid inactivation of just‐released acetylcholine.

Effect of “disuse” on mammalian fast-twitch muscle: Joint fixation compared with neurally applied tetrodotoxin

The effect of disuse on the functional properties of fast-twitch mammalian muscle is controversial, perhaps because the various disuse models reduce activity to different degrees, and may introduce factors other than reduced activity per se. Our goal was to compare the effects of 14 days of disuse produced by neurally applied tetrodotoxin and joint fixation (knee and ankle) on several morphologic and functional characteristics of the rat gastrocnemius. Joint fixation produced a decrease in muscle wet weight and absolute tetanic tension measured in situ, and a preferential atrophy of slow-twitch fibers. The degree of atrophy was more severe with TTX-disuse and affected all fiber types to the same extent. In further contrast to joint fixation, TTX-disuse caused a preferential loss of myofibrillar protein and a decrease in tetanic tension per unit muscle wet weight. In addition, TTX-disuse resulted in an elevation of twitch:tetanic ratio, a prolonged twitch, and generated a relatively higher proportion of tetanic force at 50 Hz. The normalized maximal rate of tetanic tension development (% Po/ms) was highest in the TTX group. The fatigue index was unaffected by either intervention. The data suggest that complete disuse of mammalian fast-twitch muscle causes atrophy, prolongation of the twitch, and a loss in contractile strength per gram of tissue, and are consistent with qualitative or quantitative changes in the sarcoplasmic reticulum and a decrease in myofibrillar protein concentration with disuse.