Gender difference in motor impairments induced by chronic administration of vinblastine

Objective(s): Neurotoxicity of anticancer drugs complicates treatment of cancer patients. Vinblastine (VBL) is reported to induce motor and cognitive impairments in patients receiving chronic low-dose regimen. Materials and Methods: The effects of VBL treatment on motor, learning and memory functions of male and female Wistar rats were studied by behavioral related tests. Animals were given chronic intraperitoneal injections of VBL (0.2 mg/kg/week for 5 weeks) from postnatal day 23 to 52. Motor function was evaluated using grasping test and balancing was evaluated by the rotarod. Spatial learning and memory and anxiety-like behavior were determined using Morris water maze (MWM) task and open field test, respectively. Results: Administration of VBL caused severe damage to motor and balance function of male rats in comparison to female rats treated with VBL and rats treated with saline. Memory and locomotion were affected in both male and female rats compared with saline treated rats, while a sex difference was also observed in these parameters; male rats showed more impairment compared with female ones. Both male and female rats showed cognitive impairments in MWM task and no sex differences were observed in these functions. Conclusion: Results revealed that VBL is a potent neurotoxic agent and despite the profound effect of VBL on motor and cognitive functions, it seems that male rats are more susceptible to motor deficits induced by VBL

Patterns of variation and allometry in sub-cortical structures of the human brain: an evaluation of sex differences and age

This research tests a series of research questions concerning relationships between size, shape (static adult scaling relations) and multivariate patterns of variation in brains of adult modern humans using in vivo measurements from magnetic resonance imaging (MRI) scans. The main research questions consider if patterns of adult human sub-cortical brain dimorphisms are driven by overall brain size differences between the sexes. Sex differences in absolute brain size in humans are well known. There is a general consensus that male brains are larger in absolute size than female brains. However, discrepancies among studies in the presence and extent of dimorphisms indicate uncertainty the degree to which sexual dimorphism (SD) is spread throughout the brain, particularly within sub-cortical structures. Therefore, to address the problem of SD, this project 1) tests brain size variation and scaling relationships in sub-cortical structures between adult human males and females, 2) tests these in younger and older age categories and 3) tests the degree to which sub-cortical brain components covary in size. This study includes two groups of right-handed, native English speakers recruited from the Champaign-Urbana community. These data represent 189 healthy individuals, consisting of four sex and age categories: younger men (n=18), younger women (n=23), older men (n=50), and older women (n=98). Younger individuals ages range from 18-35 years, and older individuals ages range from 50-80 years. The individuals involved in this project were originally recruited for a study on the effects of exercise and aging on cognition (Colcombe, 2004; Erickson et. al., 2004), and were screened for psychiatric illness prior to participation. The results presented here support the hypothesis that sex differences in sub-cortical structures relative to total brain volume are moderate to non-existent between males and females ii" " both in the younger and in the older age groups. Bivariate results indicate two possible patterns of allometry: significant positive allometry with the use of a reduced major axis regression, or allometry supporting a generally isometric to negatively allometric with the use of an ordinary least squares regression. Both results are described. Multivariate results (principal components analysis) of the combined sample indicate size plays a large role in explaining the variation in the data, with other factors offering substantial contributions. On explanation is that patterns of variation in the second and perhaps third principal components might be the result of developmental and functional relationships among sub-cortical structures. The main differences between the older and younger age categories is a higher correlation among regions in the younger category, lending some support to the idea that an extended human lifespan may lead to a breakdown in correlation structure as we age. Reduced major axis regression and ordinary least squares regression offer two alternatives to understanding scaling of sub-cortical structures in the brain. OLS results are in line with expectations of scaling patterns. Issues of sample size are important to the interpretation of results in this study, and are discussed. The effects of developmental processes on adult brain size are described throughout the thesis. In particular, gonadal hormones such as estrogen and testosterone have been hypothesized to result in larger or smaller structures in each of the sexes. The potential impact these hormones have on sex differences in the brain and on behavior support the idea that hormones may play a large role in determining differences in function, and that may or may not result in measurable differences in brain volumes. Finally, implications of this study and avenues for future research are discussed