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D M Katz

Publications and source records attributed to D M Katz.

At least 37 records · Page 2Linked to original sources
PubMed1994

Leukemia inhibitory factor and neurotrophins support overlapping populations of rat nodose sensory neurons in culture.

Recent studies in this and other laboratories demonstrated that leukemia inhibitory factor (LIF) can regulate differentiation and survival of nerve growth factor (NGF)-dependent primary sensory neurons. To determine whether development of NGF-independent sensory neurons could be similarly regulated, the present study examined the effects of LIF and the related cytokine-like growth factor, ciliary neurotrophic factor (CNTF), on survival of rat nodose ganglion (NG) cells in culture. In addition, survival in LIF-treated cultures was compared in the presence and absence of the neurotrophins brain-derived neurotrophic factor (BDNF), NT-3, and NT-4, factors previously shown to target NG sensory neurons, to determine whether the cytokine-like factors and neurotrophins act on the same population of ganglion cells. Treatment of dissociate cultures of Embryonic Day (E) 16.5 NG with LIF or CNTF (10 ng/ml) resulted in a four- to fivefold increase in neuronal survival; the number of neurons supported by either factor represented approximately 50% of the total NG population. In contrast, less than 10% of newborn NG neurons survived in the presence of LIF or CNTF, suggesting a loss in responsiveness to these factors during fetal development in vivo. In cultures of E16.5 ganglia, BDNF, NT-3, or NT-4 alone each increased cell survival to varying degrees (BDNF > NT-4 = LIF > NT-3); NGF, on the other hand, had no effect. Combining LIF with BDNF, NT-3, or NT-4 had only partially additive effects on NG neuron number (LIF + BDNF, 36% greater than BDNF alone; LIF + NT-3, 21% greater than LIF alone; LIF + NT-4, 49% greater than NT-4 or LIF alone; P < 0.05), indicating that LIF and these neurotrophins support survival of overlapping subsets of NG neurons in culture. To begin defining whether NG neurons were capable of responding to CNTF and LIF in vivo, Northern blots were used to examine expression of mRNAs coding for CNTF and LIF receptor components (CNTFR alpha, gp130, and LIFR beta) in the intact ganglion. mRNAs for all three receptor components were present in both E16.5 and newborn ganglia, suggesting that LIF and CNTF receptors are expressed in the NG in vivo. Taken together, these data demonstrate that LIF and CNTF can support survival of NGF-independent sensory neurons in culture and indicate that cytokine-like growth factors may play a role in regulating visceral sensory development in vivo.

Animals↗
PubMed1994

BDNF supports mammalian chemoafferent neurons in vitro and following peripheral target removal in vivo.

Chemoreceptor neurons innervating the rat carotid body were used as a model system to define target regulation of visceral sensory development in fetal and newborn animals. In vitro, chemoafferents were selectively supported by coculture with the carotid body or by treatment with trkB ligands [brain-derived neurotrophic factor (BDNF) and neurotrophin-4], whereas nerve growth factor and neurotrophin 3 had no effect. In vivo, chemoafferent neurons died following carotid body removal at birth, indicating a predominant role of peripheral, rather than central, targets in mediating survival at this stage. However, in the absence of target tissues, a large proportion of carotid body afferents could be rescued by implants containing BDNF. Moreover, BDNF mRNA was detected in the newborn carotid body by reverse transcriptase polymerase chain reaction. These data provide the first demonstration that BDNF can substitute for peripheral target support of sensory neuron survival in vivo and indicate that trkB ligands may be particularly important for development of visceral afferents involved in cardiorespiratory control.

Afferent Pathways↗
PubMed1994

Shunt failure without ventriculomegaly proclaimed by ophthalmic findings.

Four patients who developed increased intracranial pressure from ventricular shunt failure suffered a delay in diagnosis because magnetic resonance imaging of the brain did not show ventriculomegaly and because ophthalmic findings were initially overlooked or misinterpreted. None of the patients had the conventional manifestations of shunt failure: severe headache, nausea, vomiting, and depressed consciousness. Three patients suffered marked, permanent vision loss from chronic papilledema. These cases affirm that increased intracranial pressure may occur in shunt dependency without producing either conventional clinical symptoms or signs on imaging of the brain. Because ophthalmic manifestations may be the major clues to diagnosis, and because irreversible loss of vision is possible if these clues are overlooked, consideration should be given to periodic ophthalmological examination of shunt-dependent patients.

Adolescent↗
PubMed1993

Non-neuronal cells inhibit catecholaminergic differentiation of primary sensory neurons: role of leukemia inhibitory factor.

Although some sensory ganglion cells in mature animals are catecholaminergic, most mammalian sensory neurons that express the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) do so only transiently during early gangliogenesis in vivo. The lack of TH expression at later stages appears to be due to modulation of this catecholaminergic potential. A previous study showed that the phenotype reappears, for example, when E16.5 and older sensory ganglia are dissociated in culture into single cells, suggesting that extracellular influences can modulate TH expression. Moreover, TH expression in dissociate cultures is cell-density dependent, as a four-fold increase in plating density led to a 30% decrease in the percentage of TH neurons. The present study demonstrates that inhibition of TH expression in high density cultures is mediated by ganglionic non-neuronal cells (NNC), as removal of NNC abolished density-dependent inhibition. Moreover, plating E16.5 trigeminal neurons at low density on top of NNC monolayers resulted in an 85% decrease in the percentage of TH neurons. Treatment of cultures with non-neuronal cell conditioned medium (NNC-CM) reproduced the effect of coculture with NNC, suggesting that diffusible factors from NNC were involved in the inhibition of TH. The inhibitory effect of NNC-CM was mimicked by treatment of dissociate cultures with ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). However, immunoprecipitation of NNC-CM with antibodies against LIF or CNTF showed that only anti-LIF antibodies were able partially to remove the TH inhibitory activity of NNC-CM. Therefore, LIF is one, but not the only, factor mediating NNC inhibition of TH expression in cultured sensory neurons. In summary, these data indicate that ganglionic NNC can regulate sensory transmitter phenotype in culture by inhibiting expression of specific molecular traits. The finding that LIF can partially account for the inhibitory effect of ganglionic NNC on TH expression suggests a novel role for this cytokine in regulating differentiation of catecholaminergic properties in sensory neurons.

Animals↗
PubMed1992

The central organization of carotid body afferent projections to the brainstem of the rat.

Despite increasing focus on brainstem respiratory control mechanisms in the rat, relatively little is known about the central organization of chemoreceptor pathways in this species. To approach this issue, the present study sought to selectively define the central projections of primary sensory neurons that innervate the carotid body. Afferent projections were visualized by horseradish peroxidase histochemistry following microinjection of wheat germ agglutinin-horseradish peroxidase into the vascularly isolated carotid body in situ. Labeled afferent fibers were found in several discrete regions of the dorsomedial and ventrolateral medulla. Heaviest labeling was seen bilaterally in the commissural and medial subnuclei of the caudal nucleus tractus solitarius (nTS); more moderate labeling was found bilaterally in the intermediate, interstitial, and dorsolateral subnuclei and ipsilaterally in the ventrolateral subnuclei. In addition, we observed a prominent projection to the caudal ventrolateral medulla in the region of the nucleus retroambigualis. Sparse labeling was also seen in the dorsal motor nucleus of the vagus nerve and the area postrema. These findings support the existence of multiple pathways by which peripheral chemoreceptor inputs may influence central respiratory neurons. In addition to the classically defined relay in nTS, carotid body afferents may also interact more directly with respiratory- or cardiovascular-related neurons in other regions such as the ventrolateral medulla.

Afferent Pathways↗
PubMed1992

Transient expression of somatostatin peptide is a widespread feature of developing sensory and sympathetic neurons in the embryonic rat.

Previous studies from this and other laboratories demonstrated that many embryonic sensory ganglion cells in the rat transiently express the catecholamine synthesizing enzyme tyrosine hydroxylase (TH), a trait not expressed by most mature sensory neurons. We, therefore, sought to determine whether transient expression was uniquely associated with catecholaminergic traits, or, alternatively, whether embryonic ganglion cells transiently expressed peptidergic properties as well. Of the four peptides examined (somatostatin [somatotropin release inhibiting factor] (SRIF), galanin (Gal), calcitonin gene-related peptide (CGRP), and substance P (SP)), only SRIF was found to be transiently expressed during early stages of sensory gangliogenesis. Surprisingly, SRIF immunoreactivity was observed in virtually all cranial and spinal sensory ganglion cells on embryonic day (E) 12.5. In addition to perikaryal labeling, intense SRIF immunoreactivity was also observed in the central and peripheral processes of E12.5 sensory neurons, suggesting the peptide may be released from nerve endings. The time course of SRIF appearance in cranial ganglion cells paralleled that previously described for TH, and double-labeling studies revealed extensive co-localization of these two phenotypes. By E16.5, however, the number of neurons expressing SRIF had diminished markedly, indicating that SRIF is only transiently expressed by most sensory neurons during early stages of ganglion development. An unexpected finding was that transient expression of SRIF is also a prominent feature of sympathetic ganglion cells; however, the temporal pattern of staining in the sympathetic and sensory ganglia differed substantially. Whereas virtually no SRIF staining was observed in E12.5 sympathetics, the vast majority of cells in the E16.5 superior cervical ganglion (SCG) were labeled. This contrasted sharply with the adult SCG, in which only low levels of SRIF expression were found. These findings demonstrate that SRIF peptide is transiently expressed at high levels in peripheral sensory and sympathetic neurons during embryogenesis. The time course and widespread distribution of SRIF expression indicates that the peptide may play a role in early stages of ganglion cell growth and development. Moreover, these data, in conjunction with previous studies demonstrating SRIF immunoreactivity in developing central neurons, suggest that transient expression of this peptide is a common property of diverse neuronal cell types.

Animals↗
PubMed1992

Transmitter diversity in carotid body afferent neurons: dopaminergic and peptidergic phenotypes.

Hypoxic stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15-20 microns) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20-29 microns) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic "efferent" inhibition in the carotid body.

Animals↗
PubMed1991

A catecholaminergic sensory neuron phenotype in cranial derivatives of the neural crest: regulation by cell aggregation and nerve growth factor.

Tyrosine hydroxylase (TH) is transiently detectable in cells distributed throughout cranial sensory ganglia during early stages of gangliogenesis [embryonic day (E) 10.5-15.5]. Although TH cells appear in embryonic ganglia of both neural crest and placode origin, mature cranial sensory neurons that express catecholaminergic properties are restricted to placode derivatives. The mechanism(s) underlying the loss of TH expression in crest-derived sensory ganglia is unknown, and the present study was undertaken to define the temporal regulation of this phenotype. Our data indicate that transient TH cells belong to a large subset of primary sensory neurons that exhibit the capability to express TH throughout development. The lack of TH expression after E15.5 appears to be due to modulation of this catecholaminergic potential. The phenotype reappears, however, when E16.5 and older ganglia are dissociated in culture into single cells, suggesting that factors associated with cell aggregation modulate TH expression. In support of this hypothesis, sensory neurons grown at high cell density exhibit lower levels of TH expression than low-density cultures. The decrease in TH levels seen at high density was associated with changes in sensory neuron morphology that are characteristic of ganglion cell maturation in vivo; therefore, modulation of TH expression may be only one facet of a more general program of sensory neuron differentiation associated with cell aggregation in developing ganglia. In contrast to the effects of cell aggregation, treatment with NGF increased the proportion of TH cells in dissociate cultures of E14.5 and E16.5 cranial sensory ganglia. Our findings indicate that sensory transmitter phenotype may be modulated by multiple factors during gangliogenesis, including cellular interactions intrinsic to the developing ganglionic microenvironment.

Animals↗
PubMed1990

Developmental regulation of tyrosine hydroxylase expression in primary sensory neurons of the rat.

The regulation of transmitter phenotype in primary sensory neurons remains poorly understood. However, recent studies of catecholaminergic (CA) sensory neurons suggest that expression of this particular phenotype may be related to innervation of specific peripheral tissues. In the glossopharyngeal petrosal ganglion (PG) of adult rats, for example, the vast majority of CA sensory neurons innervate a single target, the carotid body. The present study was undertaken, therefore, to begin investigating factors that underlie CA differentiation in sensory neurons, using the rat PG as a model system. Immunocytochemical, biochemical, and morphometric methods were used to investigate the normal time course of CA development in the PG in vivo, employing tyrosine hydroxylase (TH) as a phenotypic marker. These studies revealed two temporally distinct waves of TH expression during embryogenesis. TH immunoreactivity was initially detectable on Embryonic Day (E) 11.5; the number of stained cells increased markedly by E12.5 and then fell off sharply to near 0 by E15.5. Simultaneous immunostaining for TH and neurofilament proteins revealed a high proportion of double-labeled perikarya on E12.5, indicating that the transiently TH-positive cells are neurons. A second, sustained phase of TH expression began on E16.5, and by Postnatal Day 1 adult numbers of TH-containing ganglion cells were present. Western blot analysis demonstrated that TH levels per cell rose 3.5-fold in the perinatal period, indicating that maturation of this particular catecholaminergic trait in PG sensory neurons is highly regulated around birth. Morphometric techniques were used to define the relationship between neurons that transiently exhibit TH immunoreactivity early in gangliogenesis and those that maintain enzyme expression in the mature PG. These studies revealed separate and distinct growth curves for the early and late TH cells, respectively, demonstrating that the appearance, disappearance, and reappearance of immunoreactive cells reflects the differentiation of two separate populations of PG neurons. Moreover, these data indicate that TH expression in the population of CA cells that persists in the mature PG begins around E16.5. This is after peripheral target innervation has begun, raising the possibility that neuron-target interactions regulate biochemical differentiation of these CA sensory neurons.

Aging↗
PubMed1990

Trophic regulation of nodose ganglion cell development: evidence for an expanded role of nerve growth factor during embryogenesis in the rat.

Peripheral sensory neurons are derived from two distinct embryonic tissues, the neural crest and epibranchial placodes. Studies in the chick suggest that embryonic lineage and trophic dependence are interrelated, such that many crest-derived cells depend on NGF for survival during development, whereas placodal derivates, including nodose ganglion neurons, do not (30). It remains controversial, however, whether or not a similar dichotomy exists in mammalian species, in which trophic requirements during early development of placodal ganglia have not been defined. To approach this issue, the present study examined the effects of nerve growth factor (NGF) on neuronal survival in embryonic rat nodose ganglion cultures. Treatment of E13.5-14.5 nodose explants with 20 ng/ml NGF resulted in a four-fold increase in neuronal survival that was blocked by anti-NGF antiserum. Increased neuronal survival and neurite outgrowth were also observed in neuron-enriched dissociated cell cultures; these effects were seen within 12 h of plating, indicating that NGF-responsive neurons or neuroblasts were already present in the ganglion at the time of explantation. This was further supported by immunocytochemical staining of nodose cell bodies in situ with the monoclonal antibody 192-IgG against the NGF receptor (12). These findings indicate that NGF may be important in regulating nodose development during early gangliogenesis in mammals and suggest that NGF plays a more widespread role in peripheral nervous system ontogeny than previously recognized.

Animals↗
PubMed1988

Brain astrocytes express region-specific surface glycoproteins in culture.

Astrocytes derived from the mouse brain mesencephalon and striatum regulate neuronal morphogenesis in a region-specific manner in vitro. To begin defining molecular mechanisms that may underlie this functional heterogeneity, lectin probes were used to compare surface glycoproteins expressed by astrocytes from different brain regions. These experiments demonstrated marked differences in surface glycoproteins depending on the anatomic origin of the astrocytes. In particular, mesencephalic and cerebellar astrocytes express a fucosylated glycoprotein with an apparent molecular weight of 190 kD that is absent or rarely expressed by striatal or cortical astrocytes. These findings raise the possibility that carbohydrate diversity of astrocyte surface molecules may play a role in the heterogeneity of region-specific neuron-glial interactions.

Animals↗
PubMed1987

Low-affinity binding of [3H]imipramine to primary astrocyte cultures.

High-affinity uptake of serotonin (5-HT) by primary cultures of rat cortical astrocytes has been shown recently to be potently inhibited by tricyclic antidepressants in a manner similar to that described for brain synaptosomes [Katz and Kimelberg, J. Neurosci. 5, 1901 (1985)]. Since the high-affinity binding of [3H]imipramine (IMI) to brain membranes has been well correlated with the inhibition of synaptosomal 5-HT uptake, the binding of [3H]IMI to these astrocyte cultures was examined. No evidence for the existence of a high-affinity binding site was detected in either intact astrocytes or membranes prepared from astrocyte cultures. However, a very dense population of low-affinity binding sites was observed using both methods. This site was similar in affinity (0.606 microM for membranes and 0.959 microM for intact cells) to a low-affinity site observed with rat brain membranes (1.79 microM) but was present at a much greater density in astrocytes (1610 pmoles/mg protein for membranes and 672 for intact cells versus 53 pmoles/mg protein in brain), and may have prevented detection of the high-affinity site. Low-affinity binding to astrocytes was sodium independent, as was low-affinity binding to brain membranes. There was a poor correlation between the inhibitory potencies of the drugs tested against imipramine binding and 5-HT uptake. The binding of 15 nM [3H]IMI was nearly equipotently inhibited by all of the antidepressants tested with IC50 values ranging from 0.56 to 2.6 microM. Other receptor ligands such as 5-HT, chlorpheniramine, quipazine, atropine and benztropine were relatively weak inhibitors of [3H]IMI binding, whereas chlorpromazine was more potent than the tricycle antidepressants.

Animals↗
PubMed1987

Intravital microscopy of capillary hemodynamics in sickle cell disease.

Direct intravital microscopic examinations were made in nailfold capillaries in subjects with homozygous sickle cell disease (HbSS red cells). In the resting state, capillary red cell (rbc) flux exhibited greater intermittence compared with normal subjects, which increased with painful crisis. In crisis-free HbSS subjects, capillary occlusion and red cell sequestration occurred in only 8.2% of all capillaries and diminished to 5.8% during crisis, possibly due to sequestration of less deformable rbcs in other organs. Velocities of rbc's (Vrbc) were measured by video techniques under resting conditions and during postocclusive reactive hyperemia (PORH) induced by a pressure cuff around the finger. Resting Vrbc was normal in crisis-free HbSS subjects, averaging 0.7 mm/s. In contrast, Vrbc was significantly elevated during crisis, to 0.98 mm/s, apparently due to compensatory arteriolar dilation. Crisis subjects exhibited a significantly depressed PORH with the ratio of peak red cell velocity to resting values reduced by 15% due to a loss of vasodilatory reserve, whereas crisis-free subjects exhibited a normal response. A 55% increase in the time to attain peak Vrbc was attributed to resistance increases, possibly resulting from red cell and leukocyte-to-endothelium adhesion during the induced ischemia.

Adult↗
PubMed1987

Catecholaminergic primary sensory neurons: autonomic targets and mechanisms of transmitter regulation.

Contrary to traditional teaching, mammalian primary sensory neurons may express catecholaminergic (CA) neurotransmitter characteristics in vivo. Sensory neurons in the nodose, petrosal, and dorsal root ganglia of rats express tyrosine hydroxylase, the rate-limiting enzyme in CA biosynthesis, and formaldehyde-induced CA fluorescence, in addition to other CA traits. These findings suggest that catecholamines may function as sensory as well as autonomic motor (e.g., sympathetic) neurotransmitters. Most CA cells in the petrosal ganglion project peripherally to the carotid body, which indicates a striking correlation between CA expression in sensory neurons and the pattern of sensory innervation. Inasmuch as petrosal ganglion afferents make synaptic contact with chemoreceptive glomus cells in the carotid body, it is likely that CA sensory neurons in the ganglion transmit chemoreceptor information to the brain stem. Comparison with sympathetic neurons indicates that some mechanisms of CA regulation, such as altered activity of tyrosine hydroxylase in response to depolarizing stimuli, are shared among sensory and traditional CA populations. Other mechanisms, including trophic regulation, appear to be distinct. Therefore, despite expression of common phenotypic traits, CA expression in diverse populations of peripheral neurons is not necessarily associated with a common repertoire of regulatory mechanisms.

Animals↗
PubMed1986

Expression and regulation of tyrosine hydroxylase in adult sensory neurons in culture: effects of elevated potassium and nerve growth factor.

To determine whether similar molecular mechanisms regulate the same proteins in diverse neuronal populations, the present study compared regulation of tyrosine hydroxylase (TOH) in placodal sensory and neural crest-derived sympathetic neurons in tissue culture. Long-term explant cultures of adult nodose and petrosal sensory ganglia (NPG) contained abundant TOH-immunoreactive neurons and exhibited TOH catalytic activity, as in vivo. After an initial decline during the first week of culture, enzyme activity was maintained at a stable plateau of 60% of zero time values for at least 3 weeks. However, exposure of 2-week-old cultures to depolarizing concentrations of potassium (K+; 40 mM) increased TOH activity approximately two-fold; total protein was unchanged, suggesting that the rise was due to increased TOH specific activity. Therefore, membrane depolarization in vitro appears to regulate this specific catecholaminergic (CA) trait in sensory, as in sympathetic CA cells. In sympathetic neurons, NGF regulates TOH activity throughout life. In marked contrast, TOH activity in adult NPG cultures was unchanged in the presence of 0, 10 or 100 units NGF/ml or in the presence of high concentrations of antiserum against the beta-subunit of NGF. Adult sympathetic neurons, however, grown under identical conditions, exhibited a 5- to 10-fold rise in TOH activity in the presence of NGF. Thus, unlike sympathetics, CA metabolism in adult NPG neurons is not regulated by NGF in vitro; NGF is therefore unlikely to mediate target effects on CA metabolism in placodal sensory neurons in vivo. Our findings indicate that certain mechanisms of CA regulation are shared by placodal sensory and neural crest-derived sympathetic neurons, whereas others are not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Regional differences in 5-hydroxytryptamine and catecholamine uptake in primary astrocyte cultures.

The uptake of 3H-labelled 5-hydroxytryptamine (5-HT, serotonin) norepinephrine ([3H]NE), and 3,4-dihydroxyphenylethylamine ([ 3H]dopamine, [3H]DA) was studied in primary astrocyte cultures prepared from the cerebral cortex, corpus striatum, and hippocampal regions of neonatal rat brain. Na+-dependent uptake showed marked regional differences. For [3H]5-HT the magnitude of uptake was corpus striatum greater than or equal to cerebral cortex greater than hippocampus, whereas for [3H]NE the order was hippocampus greater than corpus striatum greater than cerebral cortex. For [3H]DA, only the hippocampal cultures showed significant Na+-dependent uptake. [3H]5-HT uptake was specifically inhibited by 10(-7) M fluoxetine whereas [3H]NE uptake was preferentially inhibited by 10(-7) M desipramine. These results may reflect regional brain specialization and/or different developmental patterns of high affinity uptake of serotonin and catecholamines by astrocytes in situ.

Animals↗