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Biomedical subjects

F H Gage

Publications and source records attributed to F H Gage.

At least 19 recordsLinked to original sources
PubMed1992

Morphological and neurochemical features of cultured primary skin fibroblasts of Fischer 344 rats following striatal implantation.

In order to assess the feasibility of using primary skin fibroblasts as a donor population for genetic modification and subsequent intracerebral grafting, the present study examines the structural and neurochemical characteristics of intrastriatal grafts of isogeneic primary fibroblasts over a period of 6 months. In culture, primary skin fibroblasts obtained from a female Fischer 344 rat display robust growth, but once confluent these cells exhibit contact inhibition. Following the implantation of cultured primary cells within the striatum of other adult rats from the same inbred strain, isologous grafts stain immunohistochemically for fibronectin at 1 week, and this immunostaining persists up to 6 months. Immunoreactivity for laminin is intense within the grafts from 1 to 8 weeks, but decreases by 6 months. Astrocytes within the striatum respond dramatically to the implantation of primary fibroblasts, such that immunohistochemical staining for glial fibrillary acidic protein increases markedly from 1 to 8 weeks after implantation. Although the intensity of immunostaining for glial fibrillary acidic protein diminishes among striatal astrocytes between 8 weeks and 6 months, the astrocytic border between the grafts and striatal neuropil remains intensely immunoreactive. Capillaries within the grafts stain immunohistochemically for glucose transporter (a facilitated glucose uptake carrier) as early as 3 weeks after implantation. Following intravenous infusions of peroxidase, capillaries within fibroblast grafts do not permit the extravasation of this macromolecule at 8 weeks and 6 months. Thus, capillaries formed within intracerebral grafts of primary skin fibroblasts exhibit a functional impermeable barrier to macromolecules similar to those capillaries of the host striatum. At the ultrastructural level, grafts possess numerous fibroblasts and have an extracellular matrix filled with collagen. Reactive astrocytic processes filled with intermediate filaments are found throughout the grafts. Hypertrophied astrocytes and their processes also appear to form a continuous border between the grafts and striatal neuropil. Grafts of primary fibroblasts also possess an extensive vasculature that is composed of capillaries with nonfenestrated endothelial cells; the occurrence of reactive astrocytic processes closely associated with or enveloping capillaries is variable. These results provide direct morphological and neurochemical evidence for the long-term survival of isologous fibroblasts after implantation within the rat striatum. From these data, we propose that isologous skin fibroblasts can be considered as donor candidates for successful intracerebral grafting following gene transfer.

Animals↗
PubMed1992

Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants.

Vulnerability of specific brain regions and neuronal populations is a characteristic feature of Alzheimer disease and Down syndrome. Cholinergic neurons of the basal forebrain degenerate in both disorders. The basis for neuronal degeneration is unknown. Mouse trisomy 16 (Ts 16) is an animal model of Down syndrome. We sought an experimental system in which the survival and development of Ts 16 basal forebrain cholinergic neurons could be examined beyond the fetal period. As Ts 16 mice do not survive birth, we transplanted fetal Ts 16 and control basal forebrain into the hippocampus of young adult mice. Transplanted neurons survived and grew neurites in all grafts. Over time, we observed selective atrophy of cholinergic neurons in Ts 16 grafts. Denervation of the hippocampus produced a significant increase in the size of Ts 16 cholinergic neurons. This suggests that hippocampal-derived neurotrophic factors acted to prevent degeneration. beta/A4-amyloid-containing plaques were not seen. Ts 16 provides a model of spontaneous, genetically determined neurodegeneration that may be used to understand better the molecular pathogenesis of neuronal dysfunction in Alzheimer disease and Down syndrome.

Alzheimer Disease↗
PubMed1992

Cooperative regulation of nerve growth factor synthesis and secretion in fibroblasts and astrocytes by fibroblast growth factor and other cytokines.

Acidic fibroblast growth factor (aFGF) enhances nerve growth factor (NGF) synthesis by astrocytes obtained from various brain regions. NGF secretion by fibrous-shaped astrocytes transformed by dibutyryl-cAMP (db-cAMP) pretreatment was less than that by untreated astrocytes. However, aFGF also enhanced NGF secretion by fibrous-shaped astrocytes. The effects of various kinds of intracellular signaling modulators on NGF synthesis were examined. None of the following second messenger effectors had an effect on NGF synthesis: protein kinase C (PKC) agonist (phorbol myristate acetate (PMA)) or antagonist (sphingosine (SP)). LiCl, and ionomycin (Iono). Further, increases of intracellular cAMP by forskolin (FK) or db-cAMP have no significant effect on NGF synthesis in astrocytes under a standard culture condition. However, NGF synthesis by astrocytes in the presence of aFGF was significantly enhanced by db-cAMP, but not by FK or sodium butyrate. These results indicate that an excessive amount of cAMP enhances the effect of aFGF on NGF synthesis in astrocytes. NGF synthesis in astrocytes was not affected by treatment with anti-aFGF or anti-bFGF neutralizing antibodies, indicating that FGFs are not involved in the autocrine regulation of NGF synthesis in astrocytes. Transforming growth factor-beta 1 (TGF-beta 1), which inhibits some effects of FGFs, increased NGF synthesis in concert with aFGF. Furthermore, the highest NGF synthesis was observed when astrocytes were stimulated by all of the following cytokines: aFGF, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and TGF-beta 1. The mechanism regulating NGF synthesis in fibroblasts obtained from prenatal rat skin was also investigated. Acidic FGF, basic FGF (bFGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF-alpha), TGF-beta 1, IL-1 beta, and TNF-alpha were found to be regulators of NGF synthesis in skin fibroblasts. Among these cytokines, aFGF is the most potent regulator of NGF synthesis in fibroblasts. NGF synthesis by skin fibroblasts, either in the presence or absence of aFGF, was not modified by any of the following: FK, PMA, SP, LiCl, and Iono. However, db-cAMP significantly enhanced NGF synthesis in both conditions. Sodium butyrate enhanced NGF synthesis in the presence of aFGF, but not in the absence of aFGF. These results suggest that an excessive amount of cAMP and butyrate moiety regulate NGF synthesis in skin fibroblasts in different ways.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1992

Quantitative effects of cerebral infarction on spatial learning in rats.

Outcome following stroke is difficult to measure because the behavioral response to infarction is variable. We hypothesized that cognitive function, such as spatial learning, may be a reproducible and sensitive outcome variable. We developed an animal model of multifocal cerebral ischemia in order to study the effects of infarction on learning. To cause ischemia, several hundred microspheres were injected into the internal carotid arteries of rats. After ischemia, behavior was measured using a global rating and a Morris water maze. Postmortem serial brain sections were stained and the size of the infarctions was measured. We found that intracerebral microspheres caused cortical infarction and an impairment of spatial learning. This impairment was not due to occlusion of the internal carotid artery and was not found in animals who received a sham injection of saline. The degree of learning impairment was not correlated with the volume density of the infarctions or with the volume density of the remaining cerebral hemisphere. The learning impairment clearly differentiated normal from lesioned animals, and the impairment was probably due to a delay in acquisition of spatial information rather than a defect in retention or retrieval. Measurement of learning deficit after cerebral ischemia is an efficient and sensitive method for evaluating new stroke treatments and possibly for exploring structure function relationships.

Animals↗
PubMed1992

Effects of gene transfer into cultured CNS neurons with a replication-defective herpes simplex virus type 1 vector.

Vectors derived from herpes simplex virus type 1 (HSV-1) may provide useful tools for gene transfer to cells of the mammalian nervous system. We have studied the infection of cultured CNS neurons using a vector derived from an HSV-1 mutant deleted for the major HSV-1 transcriptional regulatory protein-encoding gene, IE 3. This vector, denoted Cgal delta 3, contains the E. coli lacZ gene driven by the strong promotor of the human cytomegalovirus major immediate-early gene inserted into a non-coding portion of the mutant viral genome. We studied the efficiency of Cgal delta 3 infection of rat CNS neurons at various times after cell preparation from embryonic rats, the effect of vector infection on the glia subpopulation of the neuronal cultures, and the stability of lacZ expression in infected neurons cultured under conditions optimized for neuronal differentiation and survival using an astrocyte feeder layer. Under these conditions, an HSV-derived vector is a highly efficient vehicle in vitro for short-term gene transfer to cells of the CNS. Despite the fact that this vector cannot undergo a lytic cycle, it was toxic to cultured CNS neurons and glia. Even with the use of an astrocyte feeder layer to support infected neurons, we have detected only transient expression of the lacZ gene, due either to loss of the infected cells and/or to shut off of transgene expression. Further improvements will be needed in the design of HSV vectors to allow long-term gene transfer to cultured neurons.

Animals↗
PubMed1992

Delayed treatment with nerve growth factor improves acquisition of a spatial task in rats with lesions of the nucleus basalis magnocellularis: evaluation of the involvement of different neurotransmitter systems.

Rats received bilateral lesions of the nucleus basalis magnocellularis by infusion of ibotenic acid. Fourteen days later, osmotic minipumps releasing human recombinant nerve growth factor (0.3 micrograms/day) were implanted subcutaneously. Starting one month after the lesion, spatial learning of the animals was tested using the Morris water maze. Acquisition of the task was impaired by the lesion, but treatment with nerve growth factor reduced the average latency to find the platform by approximately 9 s, which represents 28% of the lesion-induced behavioral deficit. Retention of this task and spatial acuity, tested in a trial in which the platform was not present, did not show a statistically significant improvement. Lesions of the nucleus basalis magnocellularis reduced the choline acetyltransferase activity in the neocortex, but not in the hippocampus. Treatment with nerve growth factor increased the choline acetyltransferase activity in the neocortex but not in the hippocampus. There was no significant difference in the levels of norepinephrine, dopamine, serotonin or their metabolites in the cortex or hippocampus between nerve growth factor-treated animals and lesioned control animals. There was no significant correlation between any of these neurochemical changes and behavioral performance (acquisition and spatial acuity). Treatment with nerve growth factor did not increase the number or the size of nerve growth factor receptor-immunoreactive neurons in the nucleus basalis magnocellularis. These data suggest that delayed treatment with nerve growth factor results in an improvement of spatial learning in rats with lesions of the nucleus basalis magnocellularis. A possible role for cholinergic mechanisms in this effect is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts.

The neurotrophic activity of astrocytes and fibroblasts and its regulation by various cytokines were investigated. Astrocyte conditioned medium (ACM) enhanced the survival of neurons and the proliferation of astrocytes in embryonic cortical cultures grown in serum-free defined medium. However, these results were not affected by acidic fibroblast growth factor, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and transforming growth factor-beta 1. In contrast, ACM induced choline acetyltransferase expression in septal cholinergic neurons via nerve growth factor (NGF)-dependent and -independent mechanisms. However, neither acidic nor basic fibroblast growth factor is involved in this biological activity in ACM. The cytokines listed above mainly stimulate NGF-mediated cholinergic neurotrophic activity in ACM. A combination of IL-1 beta and TNF alpha significantly enhanced choline acetyltransferase activity in septal neurons co-cultured with astrocytes, and this effect was found to be mediated by NGF produced by activated astrocytes. Effects of astrocytes on GABAergic neurons were also examined. ACM was found to increase glutamate decarboxylase activity in neuronal cultures from septum in the presence of Ara-C. However, the cytokines did not enhance this activity in ACM. Moreover, a combination of IL-1 beta and TNF alpha had no effect on glutamate decarboxylase activity in septal neurons co-cultured with astrocytes. In a final set of experiments, cholinergic neurotrophic activity in skin-derived fibroblast conditioned medium (FCM) was examined. FCM was found to possess biological activity similar to that of ACM on septal neurons grown in serum-free defined medium with Ara-C. The cytokines also enhanced NGF-mediated cholinergic neurotrophic activity in FCM. Astrocytes and fibroblasts were found to possess NGF-type and non-NGF-type cholinergic neurotrophic activity, and various cytokines were found to regulate the NGF-type cholinergic neurotrophic activity in both types of cells. NGF produced by astrocytes and fibroblasts that are activated by cytokines is likely to be important for development and regeneration of NGF-sensitive neurons in the central and peripheral nervous systems.

Animals↗
PubMed1992

Effects of choline and quiescence on Drosophila choline acetyltransferase expression and acetylcholine production by transduced rat fibroblasts.

Rat-1 fibroblasts were transduced to express Drosophila choline acetyltransferase. The presence of an active enzyme in these cells (Rat-1/dChAT) was confirmed using various methods. Rat-1/dChAT fibroblasts released acetylcholine (ACh) into the culture medium. Moreover, intra- and extracellular levels of ACh could be increased by adding exogenous choline chloride. In addition, serum starvation or confluence-induced quiescence caused an 80% decrease in recombinant choline acetyltransferase activity (compared with actively growing cells). ACh release was also repressed in quiescent fibroblast cultures. Exogenous choline could mitigate the decrease in ACh release. These results indicate that Rat-1 fibroblasts can be genetically modified to produce ACh and that ACh release can be controlled by introducing choline into the culture medium. Furthermore, these data demonstrate that the expression of the retroviral promoter used in this study decreases with the onset of quiescence; however, exogenous choline can increase the amount of ACh released by quiescent fibroblasts.

Acetylcarnitine↗
PubMed1992

Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regeneration of their axons in adult rats.

Intracerebral grafts consisting of primary fibroblasts genetically engineered to express NGF were used to assess the regenerative capacity of cholinergic neurons of the adult rat septum. Our data reveal that NGF-producing grafts sustain a significantly higher proportion of NGF receptor-immunoreactive septal neurons following axotomy (approximately 65-75%) than do grafts of noninfected fibroblasts. In addition, NGF promotes the regeneration of septal axons. Following the ablation of cholinergic septal projections to the hippocampus, NGF-producing grafts placed within the lesion cavity contain large numbers of AChE-positive axons; control grafts, on the other hand, lack such cholinergic axons. Ultrastructural examination reveals that unmyelinated axons within NGF-producing grafts use many different substrates for growth, including astrocytes and components of the extracellular matrix. Grafts of control fibroblasts possess the same cellular and matrix substrates but contain only a small population of axons, probably of peripheral origin. AChE-positive axons growing through NGF-producing grafts provide a new topographically organized input to the deafferented hippocampal dentate gyrus. Furthermore, regenerating septal axons terminate predominantly on the dendritic processes of granular neurons. The dentate gyrus ipsilateral to grafts of noninfected fibroblasts, on the other hand, remains devoid of AChE-positive fibers. From these results, we conclude that the availability of NGF is a necessary requirement to sustain axotomized cholinergic septal neurons and to promote axon regeneration and cholinergic reinnervation of dentate granular neurons by these lesioned neurons. The presence of many permissive substrates (e.g., astrocytes, basal lamina, and collagen) alone, however, is not sufficient to induce axon regrowth from adult septal neurons.

Acetylcholinesterase↗
PubMed1992

Gene transfer into established and primary fibroblast cell lines: comparison of transfection methods and promoters.

The stable transfection of immortalized Rat-1 and rat skin primary fibroblast cell lines by calcium phosphate precipitation, lipofection and electroporation methods have been examined. The lipofection method was found to be better than the other methods in terms of higher transfection efficiency and convenient use. Expression of beta-galactosidase from two different viral promoters showed that the level of transgene expression depends on the promoter strength in a particular cell type. The results presented here show that the transgene expression is extremely variable among different colonies generated from individually transfected cells. Therefore, it is necessary to examine individual colonies of cells for the production of reporter gene to obtain cell lines expressing high amounts of gene products.

Animals↗
PubMed1992

Neural transplants: prospects for Alzheimer's disease.

Neural transplantation has emerged as a useful tool for neurobiologists to investigate basic mechanisms of brain function, as well as potential therapies for neurodegenerative diseases. At present, intracerebral grafting is not a therapy for Alzheimer's disease (AD) or dementia. However, recent developments using molecular biological methodologies in combination with grafting have opened new avenues to explore new therapeutic approaches and address questions of etiology.

Aged↗
PubMed1991

Hippocampal grafts into the intact brain induce epileptic patterns.

Spontaneous hippocampal EEG activity and evoked field potentials were investigated in intact rats and in animals with fetal hippocampal grafts. Pieces of hippocampal grafts, derived from 15- to 16-day-old fetuses, were used to prepare cell suspensions and grafted directly into the intact hippocampus. Control animals received suspension grafts of the cerebellum derived from fetuses of identical age. Host hippocampal electrical patterns were monitored with chronic single electrodes or with a 16-microelectrode probe from 7 to 10 months after grafting. In contrast to previously reported high survival rates of fetal grafts in studies with damage to the host brain prior to grafting, survival of both hippocampal (60%) and cerebellar grafts (20%) was very poor in the intact hippocampus. In animals with cerebellar transplants or without surviving grafted neurons the electrical activity of the host hippocampus was indistinguishable from normal controls. In rats with hippocampal grafts short duration, large amplitude EEG spikes (up to 10 mV) were recorded, predominantly during immobility. When the EEG spikes (putative interictal spikes) were of large amplitude and contained population spikes, test evoked responses delivered to the perforant path were suppressed after the spontaneous events. In contrast, evoked responses were facilitated by interictal spikes without population spikes. The threshold of electrically induced afterdischarges did not differ significantly between groups of intact rats and animals with or without hippocampal grafts. However, in three rats with hippocampal grafts the evoked afterdischarges were associated with behavioral seizures. In two of these rats spontaneously occurring seizures were also observed. Synaptophysin-immunoreactivity demonstrated growth of the host mossy fibers into the graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1991

Partial lesion of the substantia nigra: relation between extent of lesion and rotational behavior.

Recent work, largely carried out in primate models of Parkinson's disease (PD), indicates that residual dopaminergic neurons in the midbrain and their axons to the nucleus accumbens and striatum can be stimulated to sprout collateral axons, reinnervate the striatum, and cause a behavioral recovery. We sought to create a partial lesion model of PD in the rat that would (i) mimic the pattern of cell loss in human patients in early stages of PD, and (ii) permit examination of experimental manipulations that promote sprouting of axons of the surviving dopaminergic cells in the midbrain. Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNpc) were tested weekly for rotational asymmetry following administration of apomorphine or amphetamine. After completion of behavioral testing, the animals were sacrificed and the brains immunolabeled for tyrosine hydroxylase (TH). Analysis of anatomical and behavioral data revealed a strong correlation between number of remaining TH-immunoreactive cells in the SNpc and the number of rotations induced by apomorphine. There was no significant correlation between number of remaining TH-immunoreactive nigral neurons and number of rotations induced by amphetamine. We also examined the relation between area in the denervated striatum with remaining TH-immunoreactive axons, number of TH-immunoreactive cells in the lesioned SNpc, and rotational behavior. As expected, there was a strong correlation between area innervated by TH-immunoreactive axons and number of remaining TH-immunoreactive neurons in the lesioned SNpc. Total extent of innervation was also correlated with number of apomorphine-induced rotations but not with number of amphetamine-induced rotations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1991

Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure.

To identify a suitable donor cell population for gene therapy applications to the central nervous system, primary fibroblasts isolated from skin biopsies and maintained in culture are employed as autologous cells for intracerebral grafting within the adult rat striatum. Results from the present investigation reveal that cultured primary skin fibroblasts cease to proliferate once they reach confluence; these cells are thus contact inhibited in vitro. Following implantation within the striatum, the volume of the primary fibroblast grafts, stained immunohistochemically for fibronectin, does not differ significantly at 3 and 8 weeks. The graft size is dependent on the density of the cell suspension, but not dependent on either the number of passages the cells are taken through in culture prior to grafting or on the postoperative survival period. Ultrastructural evidence reveals that at 8 weeks the grafts are composed primarily of collagen and fibroblasts with rough endoplasmic reticulum and vesicles. Reactive astrocytic processes and phagocytic cells are also present in the grafts. The grafts are extensively vascularized with capillaries composed of nonfenestrated endothelium; intercellular junctions are evident at sites of apposition between endothelial cells. It is concluded that primary skin fibroblasts are able to survive for at least 8 weeks following intracerebral implantation and continue to synthesize collagen and fibronectin in vivo. Also, the grafts maintain a constant volume between 3 and 8 weeks, thereby indicating that primary skin fibroblasts do not produce tumors. Finally, dynamic host-to-graft interactions--including phagocytic migration, astrocytic hypertrophy and infiltration within the grafts, and angiogenesis--are features that constitute the structural integration of primary skin fibroblasts grafted within the adult rat central nervous system.

Animals↗
PubMed1991

Differential expression of protein kinase C isozymes in rat glial cell cultures.

Protein kinase C (PKC) is a family of closely related enzymes implicated in molecular processes involved in growth and differentiation in a variety of cells. We studied the presence and distribution of 4 PKC isozymes in glial cell cultures of the rat hippocampus employing antisera raised against synthetic peptides predicted from the cDNA sequences corresponding to the C-terminal portion of 4 PKC isoforms, alpha, beta I, beta II, and gamma. PKC(alpha) and -(beta II), but neither PKC(beta I) nor -(gamma) isoforms were detected in glial cultures of the rat hippocampus. Anti-PKC(alpha) immunostained all glial cells, whereas anti-PKC(beta II) faintly stained about 20% of total glial cells resembling the type-2 astrocyte that were GFAP immunopositive, with few processes. Anti-PKC(beta II) did not stain about 80% of the glial fibrillary acidic protein (GFAP)-immunopositive cells with a few thick processes which resembled the type-1 astrocyte. A few cells that stained intensely with anti-PKC(beta II) were GFAP immunopositive and possessed fine, but well-developed, multiple processes. Faint PKC(beta II) immunoreactivity was also detected among anti-MBP-positive cells (possibly oligodendrocytes), RCA-1-positive cells (possibly microglia), and small, oval, anti-GFAP-positive cells. These results suggest the involvement of distinct PKC isoforms in different glial functions.

Animals↗
PubMed1991

Nerve growth factor receptor immunoreactivity in the rat septohippocampal pathway: a light and electron microscope investigation.

Nerve growth factor receptor immunoreactivity in the septohippocampal pathway of adult Fischer 344 rats was assessed at the light and electron microscope level. The medial septum possesses immunoreactive somata, dendrites, axons, and terminals. Immunostained somata are either bipolar or multipolar in appearance. Dendritic processes of immunoreactive septal neurons are categorized into two groups: proximal dendrites with smooth plasma membranes and distal dendrites with numerous swellings. Immunoreactive axons within the septum are long and slender and do not possess varicosities. At the electron microscope level, immunoreactivity is confined predominantly to the plasma membrane of cell bodies and dendrites of septal neurons, as well as to the plasma membrane of axons and terminals. Both immunoreactive and nonimmunoreactive terminals that contain clear, spherical vesicles are observed contacting immunoreactive dendrites and somata. Although accumulations of vesicles are evident within these terminals at sites of contact, distinct synaptic specializations are difficult to distinguish due to the localization of reaction product on the apposing plasma membranes. Axons possessing immunoreactivity are also observed in the fimbria-fornix pathway, a major source of afferent inputs to the hippocampus. Immunoreactive axons and terminals are topographically organized in the hippocampal dentate gyrus. The density of immunostained axons and terminals is highest immediately adjacent to the granular layer. In comparison, a moderate density of immunoreactive axons is found in the outer molecular layer and a weak density in the inner molecular, granular, and polymorphic layers. Immunoreactivity is found on the plasma membrane of small unmyelinated axons and terminals aggregated into clusters throughout the dentate gyrus. Definitive examples of axosomatic and axodendritic synapses possessing immunoreactivity presynaptically are not observed. Immunoreactive profiles within the medial septum and hippocampus also circumfuse a small number of intracerebral vessels. Ultrastructural examination reveals that immunoreactivity is present within a narrowed extension of the subarachnoid space and appears to be closely associated with the plasma membrane of leptomeningeal cell processes. The present study provides direct evidence for the cellular distribution of nerve growth factor receptor immunoreactivity in the medial septum and dentate gyrus in the adult rat and offers new insight into the ultrastructural localization of nerve growth factor receptor among septal cholinergic neurons and their efferent projections to the hippocampus.

Animals↗