Biomedical subjects

Onno Bakker

Publications and source records attributed to Onno Bakker.

4 recordsLinked to original sources

PubMed2006

Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users.

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.

Adult↗

PubMed2004

Thyroid hormone receptor expression in the human hypothalamus and anterior pituitary.

In the present study, we describe for the first time the distribution of thyroid hormone receptor (TR) isoforms in the human postmortem hypothalamus and anterior pituitary using immunocytochemistry. We used a set of polyclonal antisera raised against the specific isoforms of the human TR. The distribution of TR alpha 1, alpha 2, beta 1, and beta 2 was studied in consecutive sections of six hypothalami and pituitaries. Staining intensity showed strong interindividual variation but was consistently present in the infundibular nucleus, paraventricular nucleus, and supraoptic nucleus. In addition, strong TR immunoreactivity was observed in the anterior pituitary. Neuropeptide Y and proopiomelanocortin mRNA-positive cells in the infundibular nucleus, which were studied in three other hypothalami, appeared not to express TRs, and thus, the neurons expressing TRs in the human mediobasal hypothalamus remain to be characterized.

Aged↗

PubMed2002

TR(beta)1 protein is preferentially expressed in the pericentral zone of rat liver and exhibits marked diurnal variation.

We investigated the distribution and diurnal variation of TR(beta)1 protein expression in liver with specific antibodies against TR(beta)1. Immunohistochemistry showed a zonal distribution of TR(beta)1 with maximum expression in the pericentral zone matching some known T(3)-responsive enzyme activities in the liver, such as glutamine synthetase, cholesterol 7alpha- hydroxylase, and spot 14. Combining immunohistochemistry and image analysis we found and quantified the same zonal distribution for 5'-deiodinase type 1 as for TR(beta)1. Western blot analysis revealed a profound diurnal variation for TR(beta)1 protein expression, with highest levels at the beginning of the dark period. TR(beta)1 diurnal variation partly overlaps with the T(3)-responsive genes, cholesterol 7alpha-hydroxylase and spot 14. Furthermore, TR(beta)1 distribution along the porto-central axis does not change during the day, indicating that the zonal expression of TR(beta)1 is stable. This is the first time that zonal distribution in liver has been demonstrated for a member of the nuclear receptor family. This finding together with the observed diurnal rhythm has major implications for interpreting and timing experiments concerning the TR and its downstream actions in liver.

Animals↗

PubMed2002

Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure.

The similarities between the changes in cardiac gene expression in pathological ventricular hypertrophy and hypothyroidism suggest a role of impaired cardiac thyroid hormone (TH) action in the development of contractile dysfunction during chronic cardiac pressure overload. Here we studied the possible involvement of altered cardiac TH metabolism using a rat model of right-ventricular (RV) hypertrophy induced by pressure-overload. Pathological RV hypertrophy was indicated by decreased mRNA levels of sarcoplasmic reticulum(SR) Ca2-ATPase type 2a (SERCA2a) and myosin heavy chain a (MHCalpha), and increased levels of MHCbeta mRNA. Enzyme activity of type HI deiodinase (D3), which converts T4 and T3 to the inactive compounds rT3 and 3,3'-T2, respectively, was identified in ventricular tissue. This activity was stimulated up to five fold in hypertrophic RV, but remained unaltered in the non-hypertrophic left ventricle (LV). A low level of type Ideiodinase activity was also detected, which decreased significantly in both RV and LV. Stimulation of RV D3 activity was significantly higher in those animals in which hypertrophy progressed to heart failure, compared to animals that developed compensatory hypertrophy. The induction of a cardiac TR-degrading deiodinase maybe expected to result in reduced cellular levels of T3 and thereby contribute to a local hypothyroid state in the hypertrophic and, particularly, in the failing ventricle.

Animals↗