Ultrastructure of 6-Aminonicotinamide (6-AN)-induced lesions in the central nervous system of rats

Abstract

Following a single i.p. injection of 6-AN (10 mg/kg), the anterior horn cells of 20- and 25-month-old rats increased more in size and recovered slower from chromatolytic changes than those of 3-month-old rats. Neurofilamentous hyperplasia of the perikarya was more prominent in aged rats; proliferated neurofilaments were arranged in thick parallel bundles. In the acute stage, reactive and degenerative changes of glial and mesenchymal elements were more conspicuous in 3-month-old rats; however, they disappeared by day 14 with prominent proliferation of hypertrophic astrocytes. The older rats showed less intensity and slower progression of these changes; sponginess and swelling of the astrocytic cytoplasm were still observed at day 14. Our results suggest that these age-dependent changes in the response to neurotoxins are not only induced on the neuron without mitotic phenomena after birth, but also on neuroglial cells. Furthermore, an alteration or reduction in the support of the neuron augments its intensified and delayed susceptibility to neurotoxins.

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis

“…An antimetabolite of niacin and a well-known gliotoxin, 6-aminonicotinamide, is used to induce glial degeneration, especially in the gray matter of adult rats (Horita, Ishii, & Izumiyama, 1981;Schneider & Cervos-Navarro, 1974). Delivery of 6-aminonicotinamide into the spinal cords of rats induces formation of demyelination foci, while astrocytes and oligodendrocytes undergo degeneration.…”

Neurodegeneration in equine grass sickness is not attributable to niacin deficiency

“…Equine grass sickness, human acute neurologic pellagra and experimental neurologic pellagra share many similarities, including some common neuro-anatomic targets (such as enteric neurons, dorsal root ganglia and brainstem nuclei), the nature of neurodegeneration (central chromatolysis), and some key clinical signs (weight loss, anorexia, muscle weakness, ptosis, abdominal discomfort, abdominal distension, constipation, tremors, dysphagia and hypotension) [12][13][14][15][16][17][18]. Human pellagra also induces alterations in the serum amino acid profile [19,20] that resemble those reported in EGS [21].…”