Monoamine neurotransmitters and their metabolites in brain regions in alzheimer's disease: A postmortem study

1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD.     

Cholinergic signaling in the rat pineal gland

Summary 1. Innervation of the mammalian pineal gland is mainly sympathetic. Pineal synthesis of melatonin and its levels in the circulation are thought to be under strict adrenergic control of serotoninN-acetyltransferase (NAT). In addition, several putative pineal neurotransmitters modulate melatonin synthesis and secretion.2. In this review, we summarize what is currently known on the pineal cholinergic system. Cholinergic signaling in the rat pineal gland is suggested based on the localization of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), as well as muscarinic and nicotinic ACh binding sites in the gland.3. A functional role of ACh may be regulation of pineal synaptic ribbon numbers and modulation of melatonin secretion, events possibly mediated by phosphoinositide (PI) hydrolysis and activation of protein kinase C via muscarinic ACh receptors (mAChRs).4. We also present previously unpublished data obtained using primary cultures of rat pinealocytes in an attempt to get more direct information on the effects of cholinergic stimulus on pinealocyte melatonin secretion. These studies revealed that the cholinergic effects on melatonin release are restricted mainly to intact pineal glands since they were not readily detected in primary pinealocyte cultures.     

Catecholamine and indoleamine levels in chick cultured neurons and embryonic brain

Catecholamine and indoleamine levels were determined in cultured neurons from chick embryos and in the homologous embryonic cerebral hemispheres in order to study their neurotransmission systems. The seeding of a large number of cells resulted in a pure neuronal culture made of clusters interconnected by processes. Norepinephrine, which was absent from the starting material of the culture, appeared on the 2nd day and then decreased. A small amount of epinephrine was present on the 2nd day and decreased thereafter. Dopamine was not detected. In the cerebral hemispheres of chick embryos, dopamine appreared on the 10th day in ovo and increased steadily up to the 18th day. Epinephrine was also present in the cerebral hemispheres. Its level increased up to the 14th day and then decreased. Indoleamines were measured in the same material. The level of serotonin was markedly higher than that of catecholamines and it increased during cultivation. Tryptophan was already present in the starting material and its amount increased during cultivation. The level of 5-hydroxyindoleacetic acid changed like that of serotonin. In the embryonic cerebral hemispheres, the concentration of serotonin was highest on the 12th day after incubation and then decreased. Tryptophan level decreased steadily all during the embryogenesis. These results were discussed on the ground of differences in the synthesized neurotransmitters.     

Iodinated melatonin: preparation and characterization of the molecular structure by mass and 1H NMR spectroscopy

Synthetic melatonin was iodinated by treatment with potassium iodide in the presence of an oxidizing agent, Iodo-Gen. The iodination products of melatonin were extracted with chloroform and separated by HPLC. The fraction showing immunoreactivity with respect to melatonin antisera was characterized as iodomelatonin by mass spectrometry, so that the substitution of iodine had occurred at a ring carbon atom. 1H NMR spectra showed the iodine to be incorporated at the C-2 position of the indole moiety. The N-[2-(2-iodo-5-methoxy-1H-indol-3-yl)ethyl]acetamide (2-iodomelatonin) reported here is more useful than [3H]melatonin as a tracer in melatonin radioimmunoassay. This method offers also the possibility of preparing iodinated serotonin and other indoleamines for biological studies.     

Melatonin: A potential regulator of plant growth and development?

Summary Recent research has reported the presence of melatonin (N-acetyl-5-methoxytryptamine), a mammalian indoleamine neurohormone, in higher plants, indicating that melatonin may be an important metabolic regulator that has been highly conserved across biological kingdoms. Melatonin is synthesized from tryptophan in the mammalian pineal gland and a similar biosynthetic pathway was recently described in St. John's wort shoot tissues, wherein radiolabel from tryptophan was recovered in serotonin and melatonin as well as indoleacetic acid. There is growing information describing melatonin control of physiological processes in mammals, yeast, and bacteria, including diurnal responses, detoxification of free radicals, and environmental adaptations. However, at the current time, there is no known specific role for melatonin in plant physiology. Alterations in melatonin concentrations in plant tissues have been shown to affect root development, mitosis, and mitotic spindle formation. The recent advancements in melatonin research in plants and some directions for important areas of future research are reviewed in this article.     

Effects of Injury on the Indoleamines in Cerebral Cortex

It was shown previously that focal cortical freezing lesions in rats cause widespread depression of local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere. This was interpreted as reflecting functional depression. The underlying mechanisms were postulated to involve alterations of biogenic amine systems. Accordingly, levels of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and its precursor tryptophan were determined by an HPLC method with electrochemical detection in frontoparietal cortical areas of both hemispheres at 4 h and 1, 3, 6, 8, and 10 days after a unilateral cortical freezing lesion. The 5-HT content was significantly lower than normal in the lesioned hemisphere only at 24 h, whereas the 5-HIAA level peaked at 24 h but was significantly elevated above normal values between 4 h and 6 days after lesioning. No changes were noted in 5-HT and 5-HIAA contents in the hemisphere contralateral to the lesion. These results indicate that cortical 5-HT metabolism is increased throughout the lesioned hemisphere of a focally injured brain. The increase in tryptophan content of the lesioned brain appeared to have a time course more closely related to previously demonstrated changes in cortical LCGU than to the increase in 5-HIAA content.