methylazoxymethanol and Borna-Disease

This review examines neuroanatomical and functional alterations in rodents resulting from postnatal insults during cerebellar development. Treatments such as irradiation and methylazoxymethanol (MAM) administration produced near birth (< postnatal day 8 for irradiation treatment and < postnatal day 4 for MAM administration) result in more severe cerebellar damage than do similar treatments administered several days after birth. Prominent among the more severe alterations are foliation abnormalities, misalignment of Purkinje cells and continued multiple innervation of climbing fibers; few or none of these occur as a result of later treatments (> postnatal day 8 for irradiation treatment and > postnatal day 4 for MAM treatment). The functional alterations also differ: insults produced near birth result in hypoactivity, ataxia, tremor and accompanying learning deficits, whereas those produced later result in hyperactivity and few learning deficits. This hyperactivity may have relevance to human disorders. Brief discussions of cerebellar and functional alterations (e.g., hyperactivity) resulting from neonatal infection with the Borna disease virus and induction of hypo- and hyperthyroidism during the preweaning period are also presented.

Topics: Animals; Animals, Newborn; Borna Disease; Cerebellar Diseases; Cerebellum; Methylazoxymethanol Acetate; Mice; Rats; Teratogens