Mechanical unloading and food restriction (FR) are leading causes of bone loss, which increase the risk of fracture later in life. Leptin, a 16kDa cytokine like hormone principally produced by white adipocytes, may be involved in bone metabolism with physiological or mechanical changes causing bone loss. The hypotheses of the first study were aimed at determining if serum leptin is reduced by unloading or FR. The serum leptin level reduced by unloading or by global FR, is associated with the decline in bone formation rate. It was conjectured that decreased serum leptin may be due to reduced adipocyte number/size and/or sympathetic nervous system (SNS) activation of betaadrenoreceptors with unloading or FR, inhibiting the release of leptin from adipocytes. In the second experiment, we tested whether leptin or beta-adrenoreceptor blockade attenuates bone loss during unloading and whether such an effect due to beta blockade is associated with changes in serum leptin level. Beta-blockade mitigated unloading induced reduction in serum leptin and also beta blockade was as effective as leptin administration in mitigating a reduction in cancellous bone mineral density with unloading through both stimulation of bone formation and suppression of resorption. It was previously demonstrated that energy restriction (ER) is a major contributor to the bone loss during global FR. In the third study, we tested whether beta- blockade attenuates bone loss during ER and whether such an effect is associated with changes in serum leptin level and leptin localization in bone tissues. Beta blockade attenuated the ER induced reduction in serum leptin level, cancellous bone mineral density and bone formation rate, and also abolished the ER induced increase in bone resorption. Reduction in leptin expression in bone marrow adipocytes observed with ER was attenuated by beta-blockade. Reduction in the number of cells (bone lining cells, osteocytes and chondrocytes in cartilage) which are stained positive for leptin was also attenuated by beta-blockade. Collectively, these data identify circulating leptin effects on preventing bone loss during mechanical unloading or energy restriction. Also beta blockade is associated with mitigating reduction in serum leptin and subsequently with mitigating reduction in bone mass with unloading or ER.

To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30. min of LAD coronary arterial occlusion (CAO) were studied 3. h after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50. Hz; 0.2. ms; 90% of motor threshold, starting 15. min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis.