Differential involvement of hippocampal serotonin1A receptors and re-uptake sites in non-cognitive behaviors of Alzheimer's disease.
ABSTRACT Previous studies have shown extensive serotonergic deficits in the hippocampus of Alzheimer's disease (AD) patients. However, it is unclear whether such deficits play a role in non-cognitive, neuropsychiatric behaviors that occur frequently in AD and cause significant caregiver distress.
In this study, we aimed to correlate serotonergic markers in the AD hippocampus with neuropsychiatric behaviors.
Using postmortem hippocampal homogenates from aged controls as well as a cohort of longitudinally assessed AD patients, measurements of 5-HT(1A) receptors, 5-HT(2A) receptors, and serotonin re-uptake (5-HTT) sites were performed by binding with (3)H-labeled 8-OH-DPAT, ketanserin, and citalopram, respectively.
Alterations of 5-HT(1A) receptors and 5-HTT were found to be differentially involved in neuropsychiatric behaviors, with loss of 5-HT(1A) receptors specifically correlated with depressive symptoms, while 5-HTT sites were preserved or up-regulated in patients with aggressive behaviors.
Our data suggest that neuropsychiatric behaviors in AD share certain neurochemical features with psychiatric disorders like major depression and that serotonergic drugs used in psychiatric disorders may also be efficacious against behavioral symptoms in AD.
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ABSTRACT: Aspartic acid, 5-hydroxyindoleacetic acid, glutamic acid, homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol was determined in samples of ventricular fluid from 82 subjects. Laminar distribution of the total number (Bmax value) of serotonin 1A receptors was determined on seven neurosurgical samples of neocortex. Apart from an association in a small subgroup of subjects between homovanillate concentration and corticosteroid medication, no complicating influences of treatment preceding operation were found. The content of the serotonin metabolite alone was significantly reduced in intractable depressive illness (bipolar and major depressive disorders) compared with neurological conditions subdivided into Alzheimer's disease, other dementias and other conditions. There was no other significant difference between these groups for the compounds measured. The total number of serotonin 1A receptors was highest in the superficial layers, being considerably higher than in the rat, irrespective of cortical layer. This part of the study indicated that these receptors are important for regulating activity of human corticocortical glutamatergic neurons. The results are discussed in relation to treating depression with serotonergic agents and targeting corticocortical glutamatergic neurons as well as acetylcholine in Alzheimer's disease.Journal of Neurology Neurosurgery & Psychiatry 02/1993; 56(1):80-4. · 4.92 Impact Factor
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ABSTRACT: It is now well accepted that graphic methods are a poor choice of analytical technique for analyzing radioligand binding data given the complexity of some radioligand-binding sites interactions; this is true not only for studies performed at equilibrium but also for those examining kinetic properties of the radioligand. As a consequence the computer plays an important role in all forms of radioligand binding experiments because it reduces the labor-intensive calculations associated with such experiments and it allows the use of more appropriate weighted nonlinear curve-fitting techniques that more accurately describe the radioligand-binding site interaction. This paper describes a collection of four programs (KINETIC, EBDA, LIGAND, and LOWRY) that can be used to analyze most forms of radioligand binding experiments. The programs have been adapted for use on an IBM PC, which is a popular, inexpensive microcomputer and which is well suited to the analysis of radioligand binding data.Journal of Pharmacological Methods 12/1985; 14(3):213-28.
- Neuroreport 01/2002; 13(9):1175-1178. · 1.40 Impact Factor