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D C German

Publications and source records attributed to D C German.

At least 55 records · Page 3Linked to original sources
PubMed1991

Amphetamine-induced and spontaneous release of dopamine from A9 and A10 cell dendrites: an in vitro electrophysiological study in the mouse.

d-Amphetamine (d-AMP) is a potent releaser of dopamine (DA), and its central nervous system stimulant action is mediated primarily through its effect on the substantia nigra and ventral tegmental area dopaminergic neurons (nuclei A9 and A10, respectively). The purpose of the present experiment was to use electrophysiological techniques to examine dendritic release of DA in the in vitro slice preparation, and determine whether: (1) d-AMP inhibits the firing rates of both A9 and A10 cells; (2) the d-AMP-induced inhibition is mediated via the dendritic release of DA; and (3) there is spontaneous dendritic release of DA. Superfusion with d-AMP (2-100 microM) produced identical inhibitory dose-response curves for A9 and A10 cells, and a dose of 6.25 microM caused more than 50% inhibition in the cell firing rates. The d-AMP-induced inhibition was attenuated by blocking DA synthesis. Either D2 receptor blockade (sulpiride, 1 microM), or DA synthesis inhibition (alpha-methylparatyrosine, 50 microM) resulted in a marked increase in the firing rates of dopaminergic cells. These data suggest that d-AMP comparably releases DA from both A9 and A10 cell dendrites, that it releases newly-synthesized DA to inhibit cell firing, and that DA is tonically released to regulate cell firing rates via interactions with inhibitory D2 autoreceptors.

Action Potentials↗
PubMed1991

Nucleus A10 dopaminergic neurons in inbred mouse strains: firing rate and autoreceptor sensitivity are independent of the number of cells in the nucleus.

Inbred mouse strains have different numbers of midbrain dopaminergic neurons; for example, BALB/cJ mice have 20-25% more neurons than CBA/J mice. As the number of cells decrease, for example in Parkinson's disease and in animals with midbrain dopaminergic cell lesions, the activity of their remaining cells increases. The purpose of the present experiment was to determine whether the functional properties of dopaminergic neurons in the ventral tegmental area (nucleus A10) differ in inbred mouse strains which possess different numbers of cells. The firing rate and autoreceptor sensitivity of A10 dopaminergic cells were examined in the in vitro slice preparation in BALB/cJ, C3H/HeJ, CBA/J, and DBA/2J mouse strains. It was observed that the autoreceptors on mouse dopaminergic neurons exhibit pharmacological properties of dopamine autoreceptors; activation of the autoreceptor produced a marked inhibition (50-70%) in cell firing rate by quinpirole (10(-8) M), LY-141865 (10(-7) M), (+)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine (10(-6) M), propyl-norapomorphine (10(-5) M) and dopamine (10(-4) M), and this inhibition was blocked or reversed by specific dopamine D2 receptor antagonists [(-) sulpiride and spiroperidol, 10(-6) M]. The baseline firing rates of the A10 cells did not differ among the four inbred strains [range 2.5 +/- 0.2 (C3H/HeJ)-3.4 +/- 0.3 (CBA/J) spikes/s +/- SEM], and there was no significant difference in autoreceptor sensitivity among the mouse strains as assessed either by superfused dopamine (inhibitory dose 50% approximately 150 microM), or by superfused quinpirole (inhibitory dose 50% approximately 10 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increased midbrain dopaminergic cell activity following 2'CH3-MPTP-induced dopaminergic cell loss: an in vitro electrophysiological study.

Several days after the administration of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) to the BALB/cJ mouse there is a loss of midbrain dopaminergic neurons, a reduction of forebrain dopamine (DA) content, and an elevation in forebrain DA turnover. The purpose of the present study was to determine whether the increase in forebrain DA turnover is related to an increase in dopaminergic neuronal activity. In vitro extracellular single unit recordings were made from midbrain dopaminergic neurons in the substantia nigra pars compacta (nucleus A9) and ventral tegmental area (nucleus A10) of BALB/cJ mice. The experimental animals were treated intraperitoneally with 40, 50 or 55 mg/kg 2'CH3-MPTP and killed 7-15 days later. Forebrain DA concentrations were decreased below control values by the two higher toxin doses in the caudate-putamen (67% and 78%, respectively), but not in the nucleus accumbens. DA turnover increased more than 2-fold in the caudate-putamen, but was unchanged in the nucleus accumbens. Nucleus A9 cells, in the 2'CH3-MPTP-treated animals, exhibited a 3-fold increase in the number of spontaneously active cells, and an 84% increase in basal firing rates. There was also a positive correlation between the A9 cell firing rates, and the DA turnover in the striatum of the toxin-treated mice. Nucleus A10 cells, in the 2'CH3-MPTP-treated animals, exhibited neither changes in number of spontaneously active cells nor changes in firing rates.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Extensive survival of chromaffin cells in adrenal medulla "ribbon" grafts in the monkey neostriatum.

Experimental neurosurgical implantation of adrenal medulla tissue has been performed as a treatment for Parkinson's disease at several medical centers around the world, and similar techniques have been applied in a small number of nonhuman primates. None of these efforts to date has resulted in histological evidence of significant graft survival, and behavioral improvement in patients has been modest at best. The present series of experiments, however, has led to a novel and effective technique for stereotaxic implantation of long, narrow "ribbons" of autologous adrenal tissue in the monkey caudate and putamen nuclei. The survival and enzymatic activity of large portions of intact grafted ribbons have been demonstrated by tyrosine hydroxylase immunohistochemistry. Efforts based on other grafting techniques resulted in poor or mediocre survival, reminiscent of previously published results. Successful grafts, on the contrary, were morphologically similar to intact adrenal medulla tissue, except that neuronal processes were observed emanating from some of the transplanted cells. The success of the present technique, which minimally distorts or traumatizes adrenal and brain tissue, may be due primarily to the rapid establishment of a blood supply by anastomosis with host vessels. In most monkeys, nerve growth factor was also administered to the lateral ventricle for the duration of the graft, but excellent results were also achieved in the monkey that did not receive such treatment. We conclude that adrenal grafts made by the present technique can survive and function in primates.

Adrenal Medulla↗
PubMed1989

1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP)-induced degeneration of mesostriatal dopaminergic neurons in the mouse: biochemical and neuroanatomical studies.

The neurotoxic effects of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP), a substituted analog of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, were studied in BALB/cJ mice. Moderate doses of 2'CH3-MPTP produced a greater depletion of dopamine (DA) in the striatum (45%) than in the nucleus accumbens (23%), and in these same animals, there was a 35% loss of midbrain DA neurons. The greatest loss of DA cells occurred within the substantia nigra (43%), and there was also a significant loss of cells within the ventral tegmental area (28%). Higher doses of 2'CH3-MPTP decreased levels of DA more in the axon terminal/forebrain region (72%) than in the cell body/midbrain region (25%). Similar forebrain/midbrain DA depletion ratios were also found in mice that received an electrolytic lesion of the midbrain DA neurons; there was a greater Da depletion in the forebrain (29%) than in the midbrain (8%). In both 2'CH3-MPTP and electrolytically lesioned animals there was a significant increase in DA turnover in the forebrain region, as measured by the homovanillic acid/DA ratio. These data indicate that 2'CH3-MPTP: (1) destroys DA neurons within two midbrain regions containing cells which project to the striatum (i.e. mesostriatal DA neurons), rather than just nigrostriatal DA neurons; (2) produces a greater loss of DA in the axon terminal region than in the cell body region; and (3) influences the mesostriatal DA neurons in the same way as does a lesion to the cell bodies. These data are discussed with regard to the pathophysiology of 2'CH3-MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Midbrain dopaminergic cell loss in Parkinson's disease: computer visualization.

Computer visualization techniques were used to map the distribution of dopaminergic neurons within midbrain tissue sections from 5 parkinsonian patients and 3 age-matched control subjects. The Parkinsonian brains had over 50% fewer dopaminergic neurons within the midbrain than age-matched normal brains. The cell loss occurred within the combined substantia nigra (dopaminergic nucleus A9) and retrorubral (dopaminergic nucleus A8) areas (greater than 61%) and the ventral tegmental area (dopaminergic nucleus A10) (greater than 42%). The cell loss was greatest within the ventral portion of the substantia nigra zona compacta. The specific pattern of cell loss is very similar to the pattern of cells that project to the striatum (as opposed to cortical and limbic sites) in animal neuroanatomical tracing experiments. These data suggest that Parkinson's disease preferentially destroys midbrain dopaminergic neurons in nuclei A8, A9, and A10, which project to the striatum.

Aged↗
PubMed1989

Oral dipyridamole increases plasma adenosine levels in human beings.

Plasma adenosine levels in five healthy volunteers for 5 consecutive days showed far less intrasubject than intersubject variation (p less than 0.0001), indicating that plasma adenosine levels are relatively constant during this period. Plasma adenosine levels were then measured in a different group of five healthy subjects for a 5-day control period and during a 5-day course of oral dipyridamole at a dose of 100 mg every 6 hours. Intrasubject comparisons showed that plasma adenosine levels were significantly higher during the 5 days of dipyridamole administration than during the control period (p = 0.017) and that this increase was most significant after 48 hours of drug (p less than 0.001) administration. The average increase was 0.133 mumol/L (60%) with a range of 0.063 to 0.197 mumol/L (37% to 212%) during the last 3 days. A significant positive correlation was noted between plasma adenosine and dipyridamole levels (p = 0.001). We conclude that adenosine levels are relatively stable for an individual and are maximally increased after 2 days of oral dipyridamole.

Adenosine↗
PubMed1988

Electrophysiological and pharmacological evidence for the existence of distinct subpopulations of nigrostriatal dopaminergic neuron in the rat.

The electrophysiological and pharmacological properties of dopaminergic neurons were systematically examined throughout the anterior-posterior extent of the substantia nigra zona compacta in the rat. Cells were characterized in terms of their (1) firing pattern, (2) firing rate, (3) antidromic response properties, and (4) inhibition in firing rate following dopaminergic agonist administration. These properties were then related to the cell's position within one of four anterior-posterior segments of the nucleus. There were three types of neuronal discharge pattern encountered; irregular, burst and regular. Cells which exhibited different firing patterns exhibited different firing rates and anatomical locations within the substantia nigra zona compacta. All neurons were antidromically activated from the striatum, however, the burst- and regular-firing cells exhibited significantly faster estimated conduction velocities than irregular-firing cells. The irregular-firing cells were most sensitive to dopaminergic autoreceptor agonists whereas the burst-firing cells were most sensitive to an indirect-acting dopaminergic agonist. These experiments provide both electrophysiological and pharmacological evidence to indicate that nigrostriatal dopaminergic neurons are composed of distinct subpopulations which are characterized by their firing pattern.

Action Potentials↗
PubMed1988

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome in Macaca fascicularis: which midbrain dopaminergic neurons are lost?

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces, in both human and non-human primates, a syndrome very similar to idiopathic Parkinson's disease. The syndrome is associated with degeneration of the dopamine-containing neurons in the substantia nigra, many of which project to the neostriatum. The purpose of the present study was to quantify the regional distribution of midbrain dopamine neurons remaining after MPTP administration to the monkey (Macaca fascicularis) and to develop alternative procedures for maintaining the normal nutrition in MPTP-treated animals. Three monkeys were treated with MPTP and three served as controls. Representative sections were examined from rostral to caudal through the midbrain dopamine cell nuclei and the location of every tyrosine hydroxylase-containing cell was entered into a computer. Midbrain dopamine neuronal cell loss ranged from 36-78%, being most extensive in the two monkeys which exhibited the most severe parkinsonian syndrome. The greatest cell loss (46-93%) occurred in the substantia nigra pars compacta, or nucleus A9, and the loss was primarily in the ventral portion of the nucleus. Contrary to most previous reports, however, there was also a loss of cells in the ventral tegmental area (28-57%) and ventral reticular formation (33-87%), corresponding to nuclei A10 and A8, respectively. Since neuroanatomical tracing studies have shown that the dorsal and lateral portions of the striatum (areas showing the greatest dopamine depletion after MPTP) receive input from cells in the ventral A9 and from cells in the A8 and A10 areas, the present data suggest that MPTP preferentially destroys dopamine cells that project to the striatum (i.e. the mesostriatal cells).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Anatomical and electrophysiological characterization of presumed dopamine-containing neurons within the supramammillary region of the rat.

A combination of immunocytochemical, electrophysiological and pharmacological techniques were employed to study the properties of neurons within the supramammillary (SUM) complex of the rat. The SUM region contains a small, but dense, population of tyrosine hydroxylase immunoreactive neurons. Following injection of the orthograde neuroanatomical tracer, Phaseolus Vulgaris leucoagglutinin, into the SUM region, heavy terminal labeling was observed in the lateral septal nucleus, diagonal band of Broca and bed nucleus of the stria terminalis. The electrophysiological and pharmacological properties of antidromically-activated SUM neurons revealed evidence of two neuronal populations. Both groups of neurons exhibited long duration action potentials (greater than 2 msec) and slow conduction velocities (less than 0.5 m/sec). However, cells in one group were characterized by slow and erratic firing rates and insensitivity to dopamine (DA) autoreceptor agonists. Cells in the other group typically exhibited no spontaneous activity but could be induced to discharge by iontophoretic application of glutamate. These latter cells were sensitive to DA autoreceptor stimulation. Of the two populations of mammilloseptal SUM neurons, the silent population exhibited several properties similar to those of midbrain DA neurons.

Action Potentials↗
PubMed1988

Acute gouty arthritis and intravenous nitroglycerin.

Four adult patients with unstable angina were treated with intravenous nitroglycerin in the coronary intensive care unit. All four patients experienced an acute gouty flare while receiving or within 12 hours of discontinuing intravenous nitroglycerin. Serum uric acid levels ranged from 400 to 550 mumol/L at the time of the attack. In one patient, serum uric acid levels were followed while he was receiving intravenous nitroglycerin and were noted to increase nearly 60 mumol/L. It was speculated that the alcohol content of intravenous nitroglycerin preparations may alter serum uric acid levels and thus precipitate acute gouty flares in patients who are at increased risk for gout.

Acute Disease↗
PubMed1988

The human locus coeruleus: computer reconstruction of cellular distribution.

Quantitative neuroanatomical techniques were developed to map the distribution of norepinephrine-containing locus coeruleus (LC) neurons in the adult human brain. These neurons reside in the dorsolateral pontine tegmentum and are identifiable by their neuromelanin pigment content. Five brains, ranging in age from 60 to 104 years, were examined. Outlines of coronal or sagittal sections containing the LC were entered into a computer along with the location of each cell, certain neuroanatomical landmarks, and cell size. Sections were aligned with specific neuroanatomical landmarks so that the computer-generated distribution of cells was representative of the in situ distribution of cells. Analysis of (1) the number of cells in sections throughout the rostrocaudal extent of the nucleus, (2) cell size, (3) 3-dimensional reconstructions of the distribution of cells within the brain stem, and (4) 2-dimensional cell-frequency maps, make it possible to quantitatively characterize the distribution of cells within this large nucleus. The total estimated number of LC cells on both sides of the brain ranged from 45,562 to 18,940 (youngest to oldest), and mean soma area ranged from 835 to 718 micron 2 (youngest to oldest). The nucleus is "tube-like" in shape, has a rostrocaudal extent of approximately 16 mm, and is bilaterally symmetrical. Two-dimensional cell-frequency maps were developed to illustrate the regional distribution of cell frequencies at any rostrocaudal/mediolateral point on the horizontal plane; the total unilateral area of the LC ranged from 32.8 to 17.2 mm2 (youngest to oldest). The techniques developed to characterize the 2- and 3-dimensional distributions of LC neurons can be used in future studies to quantitatively examine the effects of aging and disease on this and other brain nuclei.

Cell Count↗
PubMed1987

Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence.

We have detected, in monkey caudate nucleus and putamen, neuronal cell bodies containing tyrosine hydroxylase-like immunoreactivity, as revealed by peroxidase-antiperoxidase immunohistochemistry. Many of these cells are distributed in an outer rim of 1-2 mm throughout the anterior-posterior extent of the neostriatum near its borders with the corona radiata; others are embedded in the adjacent white matter, especially near the ventral putamen and nucleus accumbens. Light and electron microscopy indicate that they are small (8-12 micron), bipolar cells with large nuclei. Such neostriatal neurons, containing tyrosine hydroxylase-like immunoreactivity, number in the tens of thousands.

Animals↗
PubMed1987

Hypothalamic pathology in Alzheimer's disease.

The hypothalamus was examined in 3 cases of Alzheimer's disease and 3 control brains, using combined acetylcholinesterase (AChE) and thioflavin-S staining. Neurons undergoing neurofibrillary degeneration were restricted to 3 AChE-positive cell populations (lateral tuberal, lateral posterior and tuberomammillary) that have been found in the rat and monkey to project to the cerebral cortex. Our results suggest that the neurofibrillary degeneration in the hypothalamus involves primarily neurons that innervate cortical areas involved by Alzheimer's disease. This finding is consistent with the hypothesis that Alzheimer's disease is transmitted from neuron to neuron via normal neuronal connections.

Acetylcholinesterase↗
PubMed1987

Axonal and transneuronal transport in the transmission of neurological disease: potential role in system degenerations, including Alzheimer's disease.

Neurons depend upon the processes of axonal and transneuronal transport for intra- and intercellular communication and trophic support. Experimental studies in the last decade have elucidated the mechanisms underlying these processes, and provided evidence for their role in the spread of viral and toxic diseases through the nervous system. Recent advances in neuroanatomy, and in the pathological study of certain degenerative conditions, such as Alzheimer's disease, suggest that the same principles may underlie the anatomical specificity of cell loss in a variety of system degenerations. In Alzheimer's disease, as well as in olivo-ponto-cerebellar atrophy, progressive supranuclear palsy, amyotrophic lateral sclerosis, primary autonomic failure of the Shy-Drager type, and other system degenerations, the main feature that marks the affected populations of neurons is their anatomical interconnectivity. We consider here the possibility that, in these conditions, the processes of axonal and transneuronal transport may subserve the transmission from neuron to neuron of a toxic or infectious agent, or alternatively that the diseases may result from the failure of normal transport of a trophic agent. This hypothesis not only provides a unifying framework in which to view a variety of seemingly disparate conditions, but also suggests certain approaches to identifying the causative agents.

Alzheimer Disease↗
PubMed1987

Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex.

We have used an antibody to the paired helical filament protein to immunohistochemically identify the regional distribution of subcortical nuclei containing neurofibrillary tangles in brains from Alzheimer's disease patients. Sections were examined from the cerebral cortex, diencephalon, midbrain and pons in seven Alzheimer's and three age-matched normal brains. The antibody sensitively stained the many tangles, and senile plaques, in the cerebral cortex of the Alzheimer's brains and the few tangles and senile plaques in the aged normal cortex. Ten subcortical nuclei contained many tangles in the Alzheimer's brains. The tangles were found not only within the locus coeruleus and dorsal raphe nucleus, which often have been shown to be involved in Alzheimer's neuropathology, but also within several other nuclei not previously related to this disease. For example, tangles were found in the nucleus paranigralis, peripeduncular nucleus, medial parabrachial nucleus and several midline thalamic nuclei. All of the nuclei which contained tangles have been shown, in neuroanatomical tracing studies, to project to the cerebral cortex. These data indicate that Alzheimer's disease is a disease of the cerebral cortex and the numerous subcortical nuclei which diffusely innervate it, and are consistent with the hypothesis that the cerebral cortex is the primary target of the disease and the interconnected subcortical nuclei are secondarily affected due to retrograde transport of a cortical pathogen or failure of normal transport of a trophic agent.

Afferent Pathways↗