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D J Reis

Publications and source records attributed to D J Reis.

At least 361 records · Page 20Linked to original sources

Genetic variations in midbrain dopamine cell number: parallel with differences in responses to dopaminergic agonists and in naturalistic behaviors mediated by central dopaminergic systems.

Mice of the inbred strain BALB/cJ have more midbrain dopaminergic cell bodies and greater activity of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), in the nigrostriatal and mesolimbic dopaminergic systems than mice of the CBA/J strain. This difference in cell number and TH activity in the midbrain dopaminergic systems are paralleled by differences in drug responses and behaviors which are dependent on the release of dopamine in midbrain dopaminergic system. BALB/cJ mice showed greater locomotion and stereotypy than CBA/J mice after D-amphetamine (2-20 mg/kg, i.p.). There was no difference in the amount of amphetamine accumulated in brain at the peak of drug response or in the duration of drug effect, suggesting that the differences in behavioral effect were not due to strain differences in pharmacokinetic distribution of the drug. In contrast to the greater stereotypy to D-amphetamine, BALB/cJ mice showed less stereotypy after apomorphine (2-10 mg/kg, i.p.) than CBA/J mice. BALB/cJ mice also showed more exploration than CBA/J mice, measured as locomotion and rearing in a novel open field and investigation of a novel object. Genetically determined differences in the number of midbrain dopaminergic cell bodies and in the relative density of innervation of DA terminals in target fields and in TH activity in the nigrostriatal and mesolimbic dopaminergic systems are paralleled by difference in behavioral responses mediated by release of dopamine. The number of cells of a particular neurochemical class may dictate the magnitude of behaviors, drug-induced or spontaneous, mediated by those neurons.

Animals↗

Adrenaline neurons in the rostral ventrolateral medulla innervate thoracic spinal cord: a combined immunocytochemical and retrograde transport demonstration.

Adrenaline-containing neurons in the C1 group of the ventrolateral rostral medullary reticular formation which project to the thoracic spinal cord were identified by a combined retrograde transport immunocytochemical technique. No other medullary catecholamine neurons, including the A1 and A2 noradrenaline cells, project to thoracic spinal cord. These data, taken with results of other studies of spinal catecholamine innervation, suggest a segmental segregation of projections to spinal cord by dopaminergic, noradrenergic, and adrenergic neurons.

Animals↗

Baroreflex actions of substance P microinjected into the nucleus tractus solitarii in rat: a consequence of local distortion.

Biologically active substance P (SP) (1000 ng in 0.1 microliter saline) microinjected into the nucleus tractus solitarii (NTS) of 25 rats did not affect arterial pressure, heart rate, or the baroreceptor reflex. However, microinjection of saline alone in volumes greater than 0.3 microliter consistently elicited hypotension and bradycardia followed occasionally by transient hypertension. These data suggest that previously reported cardiovascular effects of SP microinjected into the NTS resulted from local distortion.

Afferent Pathways↗

Fine structure of the nigrostriatal anlage in fetal rat brain by immunocytochemical localization of tyrosine hydroxylase.

The developmental morphology and synaptic associations of neurons in the nigrostriatal anlage are examined by the electron microscopic immunocytochemical localization of tyrosine hydroxylase at embryonic (E) day 13.5 and 14.5 in rat brain. At E 13.5, immunoreactivity for the enzyme is localized throughout the cytoplasm of neuronal perikarya and processes including somatic, dendritic, and axonal growth cones. The cytoplasmic organelles in perikarya include primarily ribonucleic-protein particles, mitochondria and an immature Golgi apparatus. At E 14.5, the tyrosine hydroxylase labeled processes are detected in the lateral hypothalamus and ventrolateral caudate-putamen. The axonal processes showing immunoreactivity in the ventral mesencephalon and more rostral portions of the nigrostriatal bundle are frequently attached to unlabeled neurites by puncta adherentia. In the hypothalamus and caudate-putamen presumably transient synaptic junctions are also detected between the labeled axons and unlabeled neurons. The immature morphological features of neurons showing immunoreactivity for tyrosine hydroxylase thus indicate, that the biochemical differentiation of the nigrostriatal neurons precedes complete cytological differentiation.

Animals↗

Antagonism of the baroreceptor reflex by glutamate diethyl ester, an antagonist to L-glutamate.

Recent reports have suggested that the excitatory amino acid L-glutamate is a neurotransmitter released by baroreceptor afferent nerves at their termination in the nucleus tractus solitarii (NTS). In this study we have examined the effect on arterial pressure, heart rate and baroreflex activity of the glutamate antagonist glutamate diethyl ester (GDEE) microinjected into the NTS of 50 rats anesthetized with Chloralose. Bilateral injections of GDEE produced dose dependent transient hypertension. The threshold dose was 2.5 micrograms/NTS and at a dose of 15 micrograms/NTS a maximal rise in arterial pressure and heart rate (from 95 +/- 8.7 mm Hg to 153 +/- 6.4 mm Hg and from 322 +/- 14.7 beats/min to 364 +/- 16.2 beats/min respectively, P less than 0.001, n = 6) occurred. A dose of 15 micrograms/NTS also completely blocked the baroreflex when injections were made bilaterally and it totally antagonized the cardiovascular effects of L-glutamate when injected immediately prior to L-glutamate. The hypertension, the antagonism of L-glutamate, and the blockade of the baroreflex persisted for 20-30 min. In that L-glutamate mediates a baroreflex-like response upon injection into NTS and in that GDEE blocks that response while at the same time blocking the naturally occurring baroreflex, the data are consistent with L-glutamate being a neurotransmitter of baroreflex afferents.

Afferent Pathways↗

Light-microscopic immunocytochemical localization of tyrosine hydroxylase in prenatal rat brain. I. Early ontogeny.

The immunocytochemical localization of tyrosine hydroxylase is examined during early ontogeny in the fetal rat brain in order to determine the age of first detection and subsequent cellular localization of the enzyme and the developmental characteristics of the immature catecholaminergic neurons. Fetal atlases of the tyrosine hydroxylase-labeled neurons are presented at embryonic day (E) 12.5, 13.5, and 14.5. Tyrosine hydroxylase is first detected immunocytochemically at E 12.5. At this stage, the labeled neurons have completed final mitosis, but are still migrating and are cytologically immature. Tyrosine hydroxylase can also be detected in axons and axonal growth cones at this stage of development. The age of first immunocytochemical detection of the enzyme precedes the demonstration of catecholamine fluorescence by 1 to 2 days in certain nuclear groups. At later stages of development (E 13.5 and E 14.5), the major groups of perikarya and processes labeled for tyrosine hydroxylase have a distribution similar to that previously described by catecholamine fluorescence. At E 14.5, the perikarya undergo considerable changes in their cytology and exhibit the first dendrites immunocytochemically labeled for the enzyme. The first terminal fields are also detected in the rudimentary caudate-putamen at this stage.

Animals↗

Light-microscopic immunocytochemical localization of tyrosine hydroxylase in prenatal rat brain. II. Late ontogeny.

The immunocytochemical localization of tyrosine hydroxylase is examined at embryonic (E) days 18 and 21 in rat brain in order to determine changes in the distribution and cytology of neurons showing immunoreactivity for the enzyme during late prenatal development. As compared with earlier stages of development, the distribution and morphology of the tyrosine hydroxylase-containing neurons at E18 and E21 more closely resemble catecholaminergic neurons in the adult brain. The changes occurring from the early to the late prenatal stages of development appear to be the result of an increase in number of cells and continued aggregation and migration of the labeled neurons. The major differences in the distribution of labeled perikarya between E18 and E21 are in the olfactory bulb and cerebral cortex. In the olfactory bulb, tyrosine hydroxylase-containing neurons are not detected until E21. In contrast in the cerebral cortex, a few neurons are transiently labeled for the enzyme at E18, but are not detected at E21 and have not been reported in the adult brain. The most striking change in the tyrosine-hydroxylase labeled structures in the late prenatal period is the increase in detectable immunoreactivity in bundles of axons and in terminal aborizations. The orderly appearance of tyrosine hydroxylase-labeled axons in the neostriatum and cortex are discussed in relation to the formation of these two contrasting regions innervated by catecholaminergic neurons.

Animals↗

Tyrosine hydroxylase activity in the superior cervical ganglion during herpes simplex virus infection: correlation with viral titers and viral antigen.

The activity of tyrosine hydroxylase (TH) was measured in the superior cervical ganglion (SCG) of the mouse during herpes simplex virus (HSV) infection. TH activity remained at control levels or actually increased during acute infection at a time when viral titers of SCG homogenates were at their peak and viral antigen was detected in from one-third to one-half of ganglionic neurons. A rapid decline in TH activity followed and coincided with falling viral titers, disappearance of viral antigen and replacement of neurons by inflammatory cells. Immunization partially prevented this reduction of TH activity. In addition, when mice were immunosuppressed by cyclophosphamide, TH activity was relatively preserved early in the course of infection despite high viral titers in the ganglion and the presence of viral antigen and histopathological alterations in nearly 100% of neurons. These results suggest that a cellular 'luxury function', in this case TH activity, can be preserved and perhaps even augmented during neuronal HSV infection. Indeed, activity of this enzyme may persist until late into the acute phase of infection, perhaps up to the point of cell death induced either by immune-mediated or direct virus-induced cell lysis.

Animals↗

Arterial hypertension elicited either by lesions or by electrical stimulations of the rostral hypothalamus in the rat.

Bilateral anodal lesions performed with stainless steel electrodes placed either in the anterior medial (AMH) or lateral (ALH) hypothalamus, or in the ventromedial nucleus (VMH), induced in unrestrained rats the rapid development of arterial hypertension, tachycardia and death. Similarly placed cathodal lesions performed with platinum electrodes failed to elicit the cardiovascular syndrome. The electrical stimulation of the AMH, ALH or VMH caused an increased in the arterial blood pressure in anesthetized rats. This pressor response was characteristically biphasic and consisted of a sharp increase in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulation. The hypertension evoked either by lesions or by stimulations of the hypothalamus, appeared to depend largely on a neurally mediated release of adrenal medullary catecholamines, and to some extent on the activation of the sympathetic vasoconstrictor fibers. Bilateral adrenalectomy, or adrenal demedullation, prevented the hypertension evoked by lesions, and selectively blocked the important secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the sympathetic vasomotor axons with 6-hydroxydopamine (6-OHDA). On the other hand, the tachycardia evoked by lesions or stimulations of the medial hypothalamus, resulted from an increase in sympathetic neural discharges to the heart, and it was abolished either by beta-receptor blockade with sotalol or by chemical sympathectomy with 6-OHDA. In contrast, the tachycardia occurring after lesions of the lateral hypothalamus was entirely due to circulating adrenal medullary catecholamines and it was eliminated by adrenalectomy. It is concluded that acute hypertension and tachycardia produced by anodal lesions performed with stainless steel electrodes results from the excitation of the hypothalamus, possibly due to the irritative action of the metallic ions deposited at the lesion sites. The observations of cardiovascular responses entirely due to adrenomedullary secretions suggests that the control of the adrenal medulla is at least partially distinct from that of the sympathetic vasoconstrictor and cardiac fibers, at the rostral hypothalamic level.

Adrenalectomy↗

Monoclonal antibodies to tyrosine hydroxylase: production and characterization.

Monoclonal antibodies were produced against tyrosine hydroxylase (TH), the enzyme catalyzing the rate limiting step in catecholamine neurotransmitter synthesis. An enzyme linked immunosorbant assay was used to detect the presence of specific antibody in culture. Specificity of the antibodies is characterized. These monospecific antibodies were used for immunoprecipitation and immunohistochemical staining of TH in brain.

Animals↗

Immunocytochemical localization of catecholamine synthesizing enzymes and neuropeptides in area postrema and medial nucleus tractus solitarius of rat brain.

The catecholaminergic and peptidergic neurons in the area postrema and adjacent portion of the medial nucleus tractus solitarii (mNTS) were characterized by the immunocytochemical localization of the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) and two neuropeptides, substance P and (Leu5)-enkephalin. The catecholamine synthesizing enzymes TH and DBH, found jointly only in noradrenergic and adrenergic neurons, were localized in cells having a similar morphology and topographical distribution. These cells were located throughout the rostrocaudal and dorsoventral extent of the area postrema, as well as in neurons within the mNTS. The processes showing TH and DBH immunoreactivity appear to form reciprocal connections between the area postrema and mNTS. Phenylethanolamine-N-methyltransferase, the enzymatic marker found only in adrenergic neurons, was detected immunocytochemically in terminals distributed throughout the area postrema and in neuronal perikarya and varicosities within the adjacent mNTS. Like the catecholamine synthesizing enzymes TH and DBH, enkephalin-like immunoreactivity was localized to perikarya, proximal processes and varicose axon terminals within the area postrema and the adjacent mNTS. However, in contrast to the widespread distribution of the enzymes, the enkephalin-like immunoreactivity was localized predominantly along the dorsal and ventrolateral margins of the area postrema. The distribution of substance P immunoreactivity, which was detected only in varicose processes, paralleled the distribution of enkephalin-like immunoreactivity, being predominantly located along the dorsal and ventrolateral margins of the area postrema. Within the mNTS adjacent to the area postrema, substance P immunoreactivity was localized to neuronal perikarya, proximal processes and varicose axon terminals. Based upon the presence of appropriate biosynthetic enzyme markers and neuropeptide localization, these findings suggest that neurons within the area postrema contain noradrenalin and enkephalin and that the afferent axons contain substance P, adrenalin and, probably, noradrenalin.

Animals↗

Projections to the spinal cord from neurons close to the ventral surface of the hindbrain in the rat.

Neurons located within 100 micron of the ventral surface of the hindbrain were labeled following injections of horseradish peroxidase into the thoracic and lumbar spinal cord in the rat. Labeled neurons were distributed into two groups, one ventrolateral to the inferior olive and ventral to the facial nucleus, and one ventral to the raphe pallidus. The location of the ventrolateral subpial group is very similar to that of the brain stem chemosensitive zones, and suggests that the neurons in this group may be important in cardiovascular regulation.

Animals↗

Immunohistochemical localization of the catecholamine-synthesizing enzymes, substance P and enkephalin in the human fetal sympathetic ganglion.

The human fetal sympathetic ganglia were studied using the indirect peroxidase-antiperoxidase PAP method for immunocytochemical demonstration of three catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) as well as the neuropeptides leucine (Leu5)-enkephalin and substance P. The neuroblasts of the ganglia showed intense peroxidase immunoreactivity for TH, moderate reaction to DBH, and no reaction to PNMT. The small intensely fluorescent (SIF) cells situated along the blood vessels also showed positive labelling for only two enzymes, TH and BDH. The immunocytochemical localization of these enzymes suggests that both neuroblasts and SIF cells synthesize noradrenalin. Neither the neuroblasts nor SIF cells showed a reaction to substance P, and only the SIF cells contained enkephalin-like immunoreactivity. The role of enkephalin in the noradrenalin-containing SIF cells is unknown, but may be related to neuromodulation of ganglionic transmission.

Catecholamines↗

Neurotransmitter-synthesizing enzymes in 14 human neuroblastoma cell lines.

Fourteen human neuroblastoma cell lines were studied for expression and regulation of neurotransmitter-synthesizing enzymes. All cell lines contained activities of adrenergic and/or cholinergic neurons and 13 expressed activities for both. None contained enzymes for serotonergic or GABAergic neurons. Enzyme activity was characteristic for a given cell line. Enzyme activity in cell lines was sensitive to growth phase, culture medium, and concentration of fetal bovine serum.

Aromatic-L-Amino-Acid Decarboxylases↗

Identification of the primary afferent fiber group and adequate stimulus initiating the trigeminal depressor response.

In anesthetized and immobilized rabbits we sought to identify the adequate stimulus and the primary afferent fiber group initiating hypotension and inhibition of sympathetic vasoconstrictor discharges in the trigeminal depressor response (TDR). In the first series of experiments we investigated the effects of electrical stimulation of different fiber groups of the infraorbital nerve on arterial pressure (AP) and renal sympathetic nerve activity (RNA). Stimulation of A-beta-fibers at frequencies between 1 and 200 Hz caused little or no reduction in AP or RNA. Recruitment of A-delta-fibers at stimulus frequencies between 1 and 30 Hz always resulted in falls in AP and RNA (by up to 30 mm Hg, and 75% of control, respectively). Decreases in AP and RNA were augmented to some extent by additional excitation of C-fibers over the same frequency range. In the second series of experiments we applied noxious or innocuous mechanical or thermal stimuli to the hairy skin of the upper lip. Hypotension and inhibition of RNA were elicited by any of the following noxious stimuli of the facial skin: (a) pricking by pins; (b) pinching by serrated forceps, (c) heating above 43% C by a contact thermoprobe; and (d) actual burning of the skin. In contrast, innocuous mechanical or thermal (below 40 degrees C) stimuli failed to diminish AP and RNA. These results indicate that noxious stimuli to the face initiate hypotension and inhibition of the sympathetic nerve activity in the TDR through activation of the A-delta primary afferent fiber group, alone or in combination with the C-fiber group.

Afferent Pathways↗

Evidence that glutamic acid is the neurotransmitter of baroreceptor afferent terminating in the nucleus tractus solitarius (NTS).

The possibility that L-glutamic acid (L-Glu) might be the neurotransmitter of baroreceptor afferents terminating in the nucleus tractus solitarius (NTS) and affecting activity of the autonomic nervous system was tested using a variety of techniques. Effects on blood pressure and heart rate of microinjections of L-Glu and antagonists into the NTS supported this contention. Use of blocking agents was confirmatory. Biochemical studies provided evidence that the agent (glutamic acid) is synthesized, stored and reaccumulated in these nerve endings. Furthermore, it was shown that L-Glu is released from the NTS in vivo. Degeneration of afferent terminals due to removal of the nodose ganglia reduced L-Glu levels in the NTS. After discussion of this and additional evidence that L-Glu is the transmitter and a consideration of reasons for eliminating other possibilities (substance P, etc.) it was concluded that L-glutamic acid is the neurotransmitter of baroreceptor afferents.

Afferent Pathways↗