| The present study aimed to assess the role of advanced age in the development and manifestation of, as well as recovery from, acute thiamine deficiency in the Fischer 344 rat using an animal model of Wernicke-Korsakoff syndrome (WKS). Interactions between pyrithiamine-induced thiamine deficiency (PTD) and age at the time of treatment, in addition to the effects of an increased recovery period, were examined relative to spatial working and reference memory impairment and neuropathology in F344 rats. Young (3-month-old), middle-aged (10-month-old), and senescent (21-month-old) F344 rats were assigned to one of two treatment conditions: PTD or pair-fed control (PF). Young and middle-aged rats in the experimental condition were further separated into two groups: those allowed a short (4-week) recovery period and those allowed an extended (8- to 12-month) recovery period. Spatial working and reference memory components were assessed with a “win-shift” radial arm maze task. After completion of behavioral testing, animals were sacrificed and multiple measures of brain pathology were obtained. Middle-aged and senescent rats exhibited seizure activity earlier in the treatment regime, as well as greater weight loss, than did young rats. Severe PTD-related brain lesions were more frequent in middle-aged and senescent rats than in young rats. There was evidence of cholinergic cell loss in senescent relative to young and middle-aged rats both in the region of the medial septal nucleus and vertical limb of the diagonal band and in the region of the horizontal limb of the diagonal band, and of PTD-related loss of cholinergic cells in the latter region across age groups. Young and middle-aged PTD-treated animals displayed the expected impairment of spatial working memory in the presence of intact reference memory relative to PF animals of comparable age.; However, senescent PF and PTD animals did not differ on either measure. Furthermore, working memory impairment was comparable among PTD animals of each age group and senescent control animals. Little convincing neurobehavioral support for an effect of extended recovery time was observed, despite some evidence of a beneficial effect of increased recovery time on working memory performance in younger rats, as well as of a detrimental effect of a longer recovery period on thalamic tissue loss across age groups. These results provide evidence for an increased susceptibility of the aged rat to the acute consequences of PTD, as observed previously (Pitkin & Savage, 2001), and indicate a similar vulnerability of the middle-aged rat to the diencephalic pathology associated with PTD despite comparability to young rats on behavioral, frontal cortical, and ChAT measures. However, further investigation into potential age-dependent neurobehavioral recovery processes is warranted in light of the inconclusive findings of the present study. |
