Altered levels of dopamine transporter in the frontal pole and the striatum in mood disorders: A postmortem study.

Dopamine dysregulation is known to play a major role in the pathophysiology of major depressive disorders (MDD) and bipolar disorders (BD). The dopamine transporter (DAT) plays a critical role in regulating dopamine concentration at the synaptic cleft and therefore could have an important role in the molecular pathology of MDD and BD. To test this hypothesis, we measured levels of [H]mazindol binding to DAT in Brodmann's area (BA) 10, BA 17 as well as in the dorsal and ventral striatum from 15 controls, 15 patients with MDD and 15 patients with BD, obtained postmortem, using in situ radioligand binding with autoradiography.

Altered levels of dopamine transporter in the frontal pole and dorsal striatum in schizophrenia.

The dopamine hypothesis proposes that there is a hypodopaminergic state in the prefrontal cortex and a hyperdopaminergic state in the striatum of patients with schizophrenia. Evidence suggests the hyperdopaminergic state in the striatum is due to synaptic dopamine elevation, particularly in the dorsal striatum. However, the molecular mechanisms causing disrupted dopaminergic function in schizophrenia remains unclear.

Muscarinic receptor binding changes in postmortem Parkinson's disease.

Parkinson's disease (PD) is a devastating disorder, affecting approximately 2% of people aged 60 and above. It is marked by progressive neurodegeneration that has long been known to impact dopaminergic cells and circuits, but more recently the acetylcholine system has also been implicated in the complex aetiology and symptomatology of the disease. While broad changes in cholinergic markers have been described, insight into the contribution of specific acetylcholine receptors is less clear.

Lower [3H]LY341495 binding to mGlu2/3 receptors in the anterior cingulate of subjects with major depressive disorder but not bipolar disorder or schizophrenia.

Introduction: The glutamatergic system has recently been implicated in the pathogenesis and treatment of major depressive disorders(MDD) and mGlu2/3 receptors play an important role in regulating glutamatergic tone. We therefore measured cortical levels of mGlu2/3 to determine if they were changed in MDD.

Methods: Binding parameters for [(3)H]LY341495 (mGlu2/3 antagonist) were determined to allow optimized in situ binding with autoradiography to be completed using a number of CNS regions.

The effect of estrogen on dopamine and serotonin receptor and transporter levels in the brain: an autoradiography study.

The aim of the present study was to elucidate the effect of estrogen on dopaminergic and serotonergic regulation of prepulse inhibition (PPI) by measuring its effects on the density of dopamine transporters (DAT), dopamine D(1) and D(2) receptors, serotonin transporters (SERT), serotonin-1A (5-HT(1A)) and 5-HT(2A) receptors using radioligand binding autoradiography. Three groups of female Sprague-Dawley rats were compared: sham-operated controls, untreated ovariectomized (OVX) rats and OVX rats with a 17beta-estradiol implant (OVX+E). These groups were identical to our previous prepulse inhibition (PPI) studies, allowing comparison of the results.

5-HT2A and muscarinic receptors in schizophrenia: a postmortem study.

Although evidence suggests that 5-HT(2A) and muscarinic M1/M4 receptors are implicated in the pathology of schizophrenia, the results are not conclusive. In the present study we tested the hypothesis that binding of 5-HT(2A) and M1/M4 receptors is altered in the postmortem brain of schizophrenia subjects. Quantitative autoradiography was employed to measure [(3)H]ketanserin binding to 5-HT(2A) receptors and [(3)H]pirenzepine binding to both M1 and M4 receptors in Brodmann's area 9 (BA9), caudate/putamen, and the hippocampal formation from six schizophrenic and six control subjects.

Expression of truncated presenilin 2 splice variant in Alzheimer's disease, bipolar disorder, and schizophrenia brain cortex.

We have analysed the expression of a truncated variant presenilin 2 protein (PS2V) in frontal cortex from subjects with Alzheimer's disease (AD) and age-matched controls, and compared these results with cortex from bipolar disorder (BP), schizophrenia (SZ) and controls in a second brain bank collection. PS2V protein was detected as a 14 kDa species with antibodies directed to the PS2 N-terminal region and to the new C-terminus created by alternative transcription. PS2V protein levels were significantly increased by two-fold in AD cortex, as compared to age-matched controls.