A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

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As Drs Patel and McGhee intimate, the original nerve mapping technique they described 1 was tedious and time-consuming, requiring the capture of hundreds of separate images and many hours of manual montaging to form a confluent map. The maps they published also had distracting component image delineation. It is for these reasons that a number of research groups have sought to develop automated techniques for generating these nerve maps (Table 1).2–6...

Inner-ear morphology of the New Zealand Kiwi (Apteryx mantelli) suggests high-frequency specialization

The sensory systems of the New Zealand kiwi appear to be uniquely adapted to occupy a nocturnal ground-dwelling niche. In addition to well-developed tactile and olfactory systems, the auditory system shows specializations of the ear, which are maintained along the central nervous system. Here, we provide a detailed description of the auditory nerve, hair cells, and stereovillar bundle orientation of the hair cells in the North Island brown kiwi. The auditory nerve of the kiwi contained about 8,000 fibers. Using the number of hair cells and innervating nerve fibers to calculate a ratio of average innervation density showed that the afferent innervation ratio in kiwi was denser than in most other birds examined. The average diameters of cochlear afferent axons in kiwi showed the typical gradient across the tonotopic axis. The kiwi basilar papilla showed a clear differentiation of tall and short hair cells. The proportion of short hair cells was higher than in the emu and likely reflects a bias towards higher frequencies represented on the kiwi basilar papilla. The orientation of the stereovillar bundles in the kiwi basilar papilla showed a pattern similar to that in most other birds but was most similar to that of the emu. Overall, many features of the auditory nerve, hair cells, and stereovilli bundle orientation in the kiwi are typical of most birds examined. Some features of the kiwi auditory system do, however, support a high-frequency specialization, specifically the innervation density and generally small size of hair-cell somata, whereas others showed the presumed ancestral condition similar to that found in the emu.

Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria

Objective Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria. Materials and Methods All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)]. Results 53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria. Conclusions IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.