Previous MRI studies consistently reported iron accumulation within the striatum of patients with Huntington's disease (HD). However, the pattern and origin of iron accumulation is poorly... Show morePrevious MRI studies consistently reported iron accumulation within the striatum of patients with Huntington's disease (HD). However, the pattern and origin of iron accumulation is poorly understood. This study aimed to characterize the histopathological correlates of iron-sensitive ex vivo MRI contrast change in HD brains. To this end, T2*-weighted 7T MRI was performed on postmortem tissue of the striatum of three control subjects and 10 HD patients followed by histological examination. In addition, formalin-fixed paraffin-embedded material of three control subjects and 14 HD patients was selected for only histology to identify the cellular localization of iron using stainings for iron, myelin, microglia and astrocytes. As expected HD striata showed prominent atrophy. Compared to controls, the striatum of HD patients was in general more hypointense on T2*-weighted highfield MRI and showed a more intense histopathological staining for iron. In addition, T2*-weighted MRI identified large focal hypointensities within the striatum of HD patients. Upon histological examination, these large focal hypointensities frequently colocalized with enlarged perivascular spaces and iron was found within the vessel wall and reactive astrocytes. In conclusion, we show that the striatum of HD patients has a distinctive phenotype on T2*-weighted MRI compared to control subjects. On ex vivo MRI, these contrast changes are heavily biased by enlarged perivascular spaces from which it is currently unknown whether this is a fixation artefact or a disease specific observation. Clinically, the observation of iron within reactive astrocytes is of importance for the interpretation and understanding of the potential underlying mechanisms of T2*-weighted MRI results in HD patients. Show less
The striatum plays a central role in the limbic system and the cholinergic system, which are both affected in AD. Therefore the striatum can be considered a key candidate structure to be affected... Show moreThe striatum plays a central role in the limbic system and the cholinergic system, which are both affected in AD. Therefore the striatum can be considered a key candidate structure to be affected early in the disease. Part one of this thesis bundled the results of several volumetric and morphometric structural MRI studies of the striatum in older people and especially in patients with AD. Identifying pathological (focal) brain atrophy is, however, complex and a simple estimation of brain structure volumes of an individual patient does not lead to a diagnosis but needs to be assessed relative to group volumes and premorbid brain size. Therefore, in part two of this thesis two large population studies were included that focused on improving our understanding of the physiologic variability of brain structure and degeneration. Show less
Bas, J.M.; Steenbergen, H. van; Pannekoek, J.N.; Fouche, J.P.; Lochner, C.; Hattingh, C.J.; ... ; Wee, N.J.A. van der 2017
Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair... Show moreAcute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1 mg/kg), the corticosterone-synthesis inhibitor metyrapone (35 mg/kg) or were left untreated I h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2 min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress may affect memory processes beyond the hippocampus and that these stress effects are due to the action of glucocorticoids. (C) 2016 Elsevier Ltd. All rights reserved. Show less
