title: 3-Acetylpyridine-induced degeneration and regeneration in the adult lizard brain: a qualitative and quantitative analysis.
abstract: The neurotoxin 3-acetylpyridine (3AP) produces highly selective neuronal damage in specific areas of the lizard brain. Following 3AP intoxication, proliferation and migration of replacement neurons born in the ventricular walls lead to regeneration of the lesioned areas. Earlier studies established the time course of 3AP-induced degeneration and subsequent regeneration in the medial cerebral cortex of adult lizards (Font, E., García-Verdugo, J.M., Alcántara, S. and Lopez-García, C., Neuron regeneration reverses 3-acetylpyridine-induced cell loss in the cerebral cortex of adult lizards, Brain Res., 551 (1991) 230-235 [13]). Complementary to our previous studies, we now provide a qualitative and quantitative account of the extent and distribution of neurotoxic damage in the brain as a whole of lizards treated with 3AP using Nissl and Golgi stains, a degeneration-sensitive reduced-silver method, and electron microscopy. Additionally, [3H]thymidine autoradiography was used to assess changes in the rate of neurogenesis caused by the 3AP treatment. Single doses of 3AP caused degenerative changes in all the cortical areas, anterior dorsal ventricular ridge, deep layers of the lateral cortex, lateral amygdaloid nucleus, and nucleus sphericus, while sparing other brain areas. The most frequent neuropathic change after 3AP treatment was clumping of the nuclear chromatin with formation of pyknotic nuclei. Occasionally, a second type of injury was observed in neurons of the cell layer of the dorsomedial cortex (DMC). 3AP also caused a conspicuous loss of dendritic spines in bipyramidal neurons of the dorsomedial and dorsal cortices possibly representing transneuronal degeneration. Numbers of [3H]thymidine-labeled cells were higher in lizards previously treated with 3AP than in controls. These results demonstrate that the neurotoxic lesion is capable of inducing an increase in the normal rate of adult neurogenesis. Whereas regeneration in the remaining areas was morphologically and histologically complete, in some animals, cell proliferation in the DMC resulted in formation of an abnormal cell plate.
authors.affiliation: Depto. Biología Animal, Fac. C. Biológicas, Universidad de Valencia, Spain. enrique.font@uv.es
authors.forename: E
authors.initials: E
authors.lastname: Font
authors.forename: E
authors.initials: E
authors.lastname: Desfilis
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Cañellas
authors.forename: S
authors.initials: S
authors.lastname: Alcántara
authors.forename: J M
authors.initials: JM
authors.lastname: García-Verdugo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D005260:Female; D008116:Lizards; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D011725:Pyridines; C010835:3-acetylpyridine; D004247:DNA; D013936:Thymidine