Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral, and anal sphincter function in a dog model. Part 3. nicotinic receptor characterization.

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response to epibatidine, expressed as percent potassium chloride, was similar (∼35% in controls, 30% in Decentralized, and 24% in ObNT-Reinn). Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). Yet, in all groups, epibatidine-induced strip contractions were similarly inhibited by mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), SR 16584 (α3ß4 neuronal nicotinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), and atropine (muscarinic receptor antagonist), indicating that nicotinic receptors (particularly α3ß4 subtypes), neuromuscular and muscarinic receptors play roles in bladder contractility. In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function.

Sleep and Circadian Rhythm Disorder in Bipolar Affective Disorder.

Symptoms of affective disorders encompass a range of changes to biological processes such as sleep and appetite. These processes are regulated over a 24-h cycle known as the circadian rhythm. Sleep is a particularly useful marker of this rhythm as it is readily measurable and functionally significant. Sleep disturbance is common in bipolar affective disorder and may act as a marker, and precipitant, of relapse. Circadian rhythms are modulated by environmental and social cues and have been shown to be influenced by treatment in BPAD. As such understanding of circadian rhythms may lead to a better understanding of the pathophysiology of BPAD and its treatment. This chapter will explore the neurobiology of the circadian clock and the putative role of circadian rhythm dysregulation in the pathophysiology and treatment of bipolar affective disorder (BPAD).