Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion

Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non-adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED

Cardiac autonomic control in individuals with Down syndrome

Our goal in this study was to compare cardiac autonomic control at rest between 50 individuals with Down syndrome and 24 control participants without disabilities. Resting autonomic function was assessed using analysis of heart rate variability. Participants with Down syndrome had reduced total heart rate variability, which indicates possible autonomic dysfunction in this population. Their VO 2 peak and BMI were not significantly correlated with resting cardiac autonomic control. This may suggest that fitness level and obesity differentially affect cardiac autonomic control in persons with Down syndrome compared to their healthy, nondisabled peers. © American Association on Mental Retardation

Normal Heart Rate with Tilt, Yet Autonomic Dysfunction in Persons with Down Syndrome

Persons with Down syndrome (DS) exhibit altered autonomic function at rest and in response to adrenergic stimuli. It is unknown whether a subset of persons with DS that have similar HR responses to a task would have similar responses in HR variability (HRV). Purpose: This study aimed to compare cardiac autonomic function during upright tilt using HRV analysis in persons with and without DS when persons with and without DS were matched for the change in HR. Methods: Persons with (25 T 2 yr; 30.4 T 1.9 kgImj2 , n = 15) and without DS (27 T 2 yr; 24.7 T 1.1 kgImj2 , n = 15) were matched on their HR response to a 5-min tilt at 80-, whereas a subset of persons with DS (28 T 3 yr; 33.5 T 2.0 kgImj2 , n = 11) were not matched for the change in HR. HRV was assessed in both the frequency (natural log transformation (Ln) of low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP)) and time domains (root mean square of successive differences [RMSSD]). Results: Changes in HR were similar in DS-matched and control but lower in DS-not matched. Tilt effects were observed for LnHF, LNTP, and RMSSD in all groups (P G 0.05). Both groups of persons with DS exhibited reduction in LnLF, with no change in the control group (P G 0.05). The increase in LF/HF was greater in the group without DS when compared with that in DS-not matched (8.71 T 2.38 vs 2.34 T 1.39, P G 0.05) but not when compared with that in DS-matched (3.59 T 1.10, P = 0.075). Conclusions: Despite similar HR response to passive upright tilt in the DS-matched, we still observed reduced sympathetic dominance in response to upright tilt in persons with D

Complexity of force output during static exercise in individuals with Down syndrome

Force variability is greater in individuals with Down syndrome (DS) compared with persons without DS and is similar to that seen with normal aging. The purpose of this study was to examine the structure (in both time and frequency domains) of force output variability in persons with DS to determine whether deficits in force control are similar between individuals with DS and older adults. An isometric handgrip task at a constant force (30% of maximal voluntary contraction) was completed by individuals with DS (n = 29, age 26 yr), and healthy young (n = 26, age 27 yr) and older (n = 33, age 70 yr) individuals. Mean, standard deviation (SD), and coefficient of variation (CV) were used to analyze the magnitude of force output variability. Spectral analysis and approximate entropy (ApEn) were used to analyze the structure of force output variability. Mean force output for DS was lower than in young controls (P < 0.05) but no different from old controls. Individuals with DS had greater SD and CV than young and old controls (P < 0.05). The DS group had a significantly greater proportion of spectral power within the 0-to 4-Hz bandwidth than the young and older controls (P < 0.05). The DS group had significantly lower ApEn values than the young controls (P < 0.05), but there were no differences in ApEn between the DS group and the old controls (P > 0.05). In conclusion, young persons with DS demonstrate enhanced temporal structure and greater amplitude of low-frequency oscillations in the force output signal than age-matched non-DS peers. Interestingly, young persons with DS and older persons without DS have similar time-dependent structure of force output variability. This would suggest a possible link between premature aging and less complex force output in persons with DS