Disease relevance of Neuroaxonal Dystrophies

• Institution of sorbinil therapy at the time of induction of STZ-D decreased, but did not completely normalize, the frequency of neuroaxonal dystrophy without altering the severity of diabetes; this finding is based on measurements of plasma glucose, body weight, food consumption, 24-h urine volume, and levels of glycosylated hemoglobin [1].
• Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease [2].
• We have developed an animal model of diabetic autonomic neuropathy that is characterized by neuroaxonal dystrophy (NAD) involving ileal mesenteric nerves and prevertebral sympathetic superior mesenteric ganglia (SMG) in chronic streptozotocin (STZ)-diabetic rats [3].
• A 7.5-year-old girl, with infantile neuroaxonal dystrophy (INAD), showed a gradual deterioration from 16 months; at age 5 years she was bedridden, with severe tetraplegia, strabismus, nystagmus and optic atrophy, and dementia [4].
• Axon degeneration is a hallmark consequence of chemical neurotoxicant exposure (e.g., acrylamide), mechanical trauma (e.g., nerve transection, spinal cord contusion), deficient perfusion (e.g., ischemia, hypoxia), and inherited neuropathies (e.g., infantile neuroaxonal dystrophy) [5].

Psychiatry related information on Neuroaxonal Dystrophies

• We investigated presence, distribution and expression of TrkA in frontal cortex from cases with Alzheimer's disease (AD), normal aging and a variety of conditions (AIDS, cystic fibrosis, cerebral infarcts) in which neuroaxonal dystrophy occurs [6].

High impact information on Neuroaxonal Dystrophies

• Treatment with low-dose insulin (to control for the transient glucose-lowering effects of IGF-I) failed to affect the frequency of ganglionic or mesenteric nerve neuroaxonal dystrophy or the severity of diabetes [7].
• Our findings (under these experimental conditions) do not support a role for aminoguanidine-sensitive processes in the development of sympathetic neuroaxonal dystrophy in diabetic rats [8].
• Chronic aminoguanidine therapy did not diminish the frequency or affect the ultrastructural appearance of neuroaxonal dystrophy in diabetic or age-matched control rat sympathetic ganglia after 7 or 10 months of continuous administration [8].
• Effect of aminoguanidine on the frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic autonomic ganglia of rats with streptozocin-induced diabetes [8].
• Quantitative studies demonstrated that markedly swollen argyrophilic terminal axons (neuroaxonal dystrophy) containing large numbers of disorganized neurofilaments developed in the SMG but not SCG as a function of diabetes, increasing age, and gender (males were more severely affected than females) [9].

Chemical compound and disease context of Neuroaxonal Dystrophies

• Animals chronically maintained on a diet containing 50% galactose, however, did not develop neuroaxonal dystrophy in excess of that found in untreated age-matched control rats [1].
• Effects of sorbinil, dietary myo-inositol supplementation, and insulin on resolution of neuroaxonal dystrophy in mesenteric nerves of streptozocin-induced diabetic rats [10].
• Inherited neuroaxonal dystrophy in C6 deficient rabbits [11].
• Stroke-like syndrome, mineralizing microangiopathy, and neuroaxonal dystrophy following intrathecal methotrexate therapy [12].
• Fourteen weeks of treatment with CP-166,572 resulted in a dramatically increased frequency of neuroaxonal dystrophy in ileal mesenteric nerves and SMG [13].

Biological context of Neuroaxonal Dystrophies

• The newly identified patient is consanguineous with the first patients reported with alpha-NAGA deficiency and neuroaxonal dystrophy and they all had the alpha-NAGA genotype E325K/E325K [14].

Anatomical context of Neuroaxonal Dystrophies

• Chronic vitamin E deficiency results in the premature and exaggerated development of neuroaxonal dystrophy (NAD) in primary sensory axon terminals in rat medullary gracile/cuneate nuclei, sites in which NAD develops normally with age [15].
• Central nervous system specimens of 4 cases of Infantile Neuroaxonal Dystrophy (Seitelberger's disease) were processed for Bodian's silver stain and for immunostaining with antibodies against neurofilaments (NF), tubulin and ubiquitin (UBQ) [16].

Gene context of Neuroaxonal Dystrophies

• Infantile neuroaxonal dystrophy is briefly described as there have been suggestions that it is a variety of PKAN, but the evidence is in favour of the two diseases being separate entities [17].
• Treatment of diabetic rats for 14 weeks with the aldose reductase inhibitor zopolrestat resulted in a significant decrease in the frequency of neuroaxonal dystrophy compared with untreated diabetics [13].
• These observations suggest that increased NGF content in sympathetic ganglia innervating the diabetic alimentary tract coupled with intact receptor expression may produce aberrant axonal sprouting and neuroaxonal dystrophy [18].
• Infantile neuroaxonal dystrophy and pantothenate-kinase-associated neurodegeneration: locus heterogeneity [19].
• Gracile neuroaxonal dystrophy (NAD) is a hallmark of the aging human and rodent sensory nervous systems which may represent an abnormal transganglionic response to peripheral axonal injury [20].

References