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PubMed2002

Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain.

Notch signaling plays a pivotal role in the regulation of vertebrate neurogenesis. However, in vitro experiments suggest that Notch1 may also be involved in the regulation of later stages of brain development. We have addressed putative roles in the central nervous system by examining the expression of Notch signaling cascade components in the postnatal mouse brain. In situ mRNA hybridization revealed that Notch1 is associated with cells in the subventricular zone, the dentate gyrus and the rostromigratory stream, all regions of continued neurogenesis in the postnatal brain. In addition, Notch1 is expressed at low levels throughout the cortex and olfactory bulb and shows striking expression in the cerebellar Purkinje cell layer. The Notch ligands, including Delta-like1 and 3 and Jagged1 and Jagged2, show distinct expression patterns in the developing and adult brain overlapping that of Notch1. In addition, the downstream targets of the Notch signaling cascade Hes1, Hes3, Hes5 and the intrinsic Notch regulatory proteins Numb and Numblike also show active signaling in distinct brain regions. Hes5 coincides with the majority of Notch1 expression and can be detected in the cerebral cortex, cerebellum and putative germinal zones. Hes3, on the other hand, shows a restricted expression in cerebellar Purkinje cells. The distribution of Notch1 and its putative ligands suggest distinct roles in specific subsets of cells in the postnatal brain including putative stem cells and differentiated neurons.

Animals↗
PubMed1994

Gene expression during ethanol withdrawal.

The expression of the proteins (C-FOS and C-JUN) encoded by the immediate early genes c-fos and c-jun was investigated in the brains of rats undergoing ethanol withdrawal. Both proteins were induced in the cerebral cortex, the piriform cortex, the olfactory bulb, the inferior colliculus, the granular cell layer of the cerebellum and in the brain stem, but only C-JUN was induced in the hippocampus of animals undergoing withdrawal without overt seizures. C-FOS was detected in the hippocampus only in animals with overt seizures. Maximal C-FOS expression occurred 15 hr after withdrawal while C-JUN was maximal at 24 hr. Gel-shift assays indicated the formation of AP-1 binding factors in nuclear extracts of the cerebral cortex, hippocampus and cerebellum 15 and 17 hr after withdrawal. These data reveal a complex pattern of immediate early gene expression during ethanol withdrawal, which may be associated with changes in neuronal plasticity underlying phenomena such as withdrawal kindling.

Animals↗
PubMed1997

D-aspartate localizations imply neuronal and neuroendocrine roles.

Though L-amino acids predominate in living organisms, substantial levels of free D-serine and D-aspartate occur in mammals, especially in nervous and endocrine tissues. Using an antibody specific for glutaraldehyde-fixed D-aspartate, we have localized D-aspartate in rat tissues. In the brain we observe discrete neuronal localizations of D-aspartate, especially in the external plexiform layer of the olfactory bulb, hypothalamic supraoptic and paraventricular nuclei, the medial habenula, and certain brainstem nuclei. In rats 3-4 weeks old, we observe D-aspartate in septal nuclei and in a subset of stellate and basket cells of the cerebellum. D-aspartate is also concentrated in glands, including the epinephrine cells of the adrenal medulla, the posterior pituitary, and the pineal gland. Levels in the pineal gland are the highest of any mammalian tissue. D-aspartate oxidase, visualized by enzyme histochemistry, is concentrated in neurons of the hippocampus, cerebral cortex, and olfactory epithelium, as well as choroid plexus and ependyma. Localizations of D-aspartate oxidase are reciprocal to D-aspartate, suggesting that the enzyme depletes endogenous stores of the amino acid and might inactivate synaptically released D-aspartate.

Amino Acid Oxidoreductases↗
PubMed1997

Selective expression of dopamine D3 receptor mRNA in proliferative zones during embryonic development of the rat brain.

We studied by in situ hybridization histochemistry the expression of D3 receptor (D3R) mRNA at various stages of rat brain development. The first expression of D3R mRNA was detected at embryonic day 14 (E14) in the striatal and rhinencephalic neuroepithelia and throughout the tectal neuroepithelium. From E16 to E19 D3R mRNA expression extended along a rostrocaudal axis to additional proliferative ventricular zones of the basal forebrain, including the neuroepithelia of the olfactory bulb, nucleus accumbens, septum, and amygdala, whereas D1 and D2 receptor (D1R and D2R) mRNAs were expressed predominantly by migrating neuroblasts and/or differentiating striatal neurons. Only a few neuroblasts, migrating in the lateral cortical stream or developing as cerebellar Purkinje cells, expressed D3R mRNA from E18. At birth D3R expression mRNA appeared in differentiating neuronal fields of the nucleus accumbens and medial mamillary body primordia and on P5 reached a distribution similar to that found in adult. In addition, a transient upregulation was detected on P5 in the medial mamillary bodies, parietofrontal cortex, and olfactory tubercle. In the adult brain D3R gene expression continued in the striatal proliferative subventricular zone. The late expression D3R mRNA in neurons, after achievement of dopamine innervation, supports the existence of a regulating factor released from dopamine neurons, as suggested by denervation studies in the adult. The sustained and abundant D3R gene expression, predominantly in germinative neuroepithelial zones actively involved in neurogenesis of most basal forebrain structures, supports the hypothesis of a neurogenetic but minor morphogenetic modulatory role for the D3R during CNS development.

Animals↗
PubMed1997

Expression of alpha 2 adrenoceptors during rat brain development--I. Alpha 2A messenger RNA expression.

The distribution of alpha 2A adrenoceptor messenger RNA expression in developing rat brain was characterized using in situ hybridization with 35S-labeled riboprobes. Intense hybridization signal was detected as early as embryonic day 14 in several areas adjacent to the forebrain and hindbrain germinal zones and in central noradrenergic neurons. A marked increase in messenger RNA expression was observed throughout the brain during late prenatal development, consistent with the migration and maturation of neurons in developing brain structures. In embryonic brain, there was a temporal and spatial correspondence in the appearance of alpha 2A messenger RNA expression and binding sites labeled with [3H]idazoxan or p-[125I]iodoclonidine, indicating translation into receptor protein at an early stage of development. Whereas the presynaptic expression remained constant throughout development, there was an early postnatal decline of alpha 2A receptor expression in many brain regions, including the olfactory bulb, cortex, caudate-putamen, hippocampus, thalamus, hypothalamus and medulla. Thereafter, messenger RNA expression increased, establishing an adult-like pattern during the second postnatal week, but remained low in areas such as the caudate-putamen, thalamus and hippocampus, which do not exhibit extensive expression in the adult. The transient perinatal expression of this alpha 2 adrenoceptor type, which coincides with a period of hyperreactivity to sensory stimuli in the locus coeruleus, may indicate a specific functional role for the alpha 2A receptor in the developing rat brain. The early and intense expression in olfactory structures suggests an involvement in early olfactory learning. The pattern of widespread, transient expression of alpha 2A receptors in the fetal brain is in marked contrast to the postnatal development of the alpha 2C receptor type.

Aging↗
PubMed1988

Ultrastructure of synaptic remodeling in piriform cortex of adult rats after neonatal olfactory bulb removal: an immunocytochemical study.

The purpose of this investigation was to study possible remodeling in synaptic structures of the piriform cortex (PC) of adult rats following neonatal deafferentation by removal of the olfactory bulb (OB) at birth. Emphasis was placed on possible qualitative changes in the ultrastructure and immunocytochemical localization of cholecystokinin (CCK, a possible excitatory neurotransmitter or modulator) and glutamic acid decarboxylase (GAD, precursor enzyme to the inhibitory transmitter GABA) in axons, terminals, and synaptic complexes. Light microscopic results in normal adult material show that GAD-positive terminals form a dense band subjacent to the lateral olfactory tract (LOT), become less dense in deeper Ib, and are rare in layer II. Following deafferentation, GAD-positive terminals appear denser and more homogeneously distributed throughout layer I and are also more prevalent in layer II. Ultrastructural results of normals and controls indicate GAD-positive terminals normally contain pleomorphic or flattened vesicles and form symmetric contacts onto dendritic shafts and branches throughout layer I. In deafferented layer I not only do there appear to be greater numbers of symmetric GAD-positive contacts, but in contrast to normals, asymmetric contacts mainly onto spines are now present. Light microscopic results from deafferented material also show an apparent proliferation with spread or sprouting of CCK-positive fibers or axonlike structures mainly into layer Ia, whereas these fibers are normally observed only in the LOT and are generally few in number. Also in normals the few CCK-positive terminals in the area subjacent to the LOT contain flattened or pleomorphic vesicles and form symmetric contacts. Deafferentation results in CCK-positive terminals throughout layer I with a greater frequency of synaptic contacts which now also include a few asymmetric contacts onto spines. The findings clearly show modifications in synaptic patterns of immunocytochemical-labeled terminals that might be compatible with the process of atypical reinnervation of deafferented postsynaptic sites and possible ingrowth of new axons.

Animals↗
PubMed1989

Visually evoked potentials are differently modulated by the basal forebrain and the nucleus cuneiformis of freely moving rat.

Different modulatory influences on visually evoked potentials (VEPs) of freely moving rats from two different cholinergic brain regions, the basal forebrain (bf, nucleus basalis magnocellularis) and the mesencephalic parabrachial nucleus cuneiformis (Cnf) are described. Bipolar stimulating electrodes were implanted in both regions and recording electrodes on the visual cortex, the frontal cortex, the olfactory bulb, and in the nasal bone. Serial electrical stimulations with increasing intensities, a series duration of 1 s, and frequencies of 100 and 10 cps, and single impulses were applied within both cholinergic regions 100 ms before light flashes. Lesions of the stimulated sites were produced to test whether modulations disappear. The bf revealed heterogeneous effects on the evoked potentials depending on the stimulation modes and on the electrode localization inside the bf whereas the Cnf modulated the evoked potentials rather uniformly. All stimulation modes in the Cnf reduced the N 30-amplitude of the primary VEP in the visual cortex simultaneously with a decrease of their peak times, and reduced the trigger rate of photically evoked afterdischarges (PhAD). 100 and 10 cps stimulation of the Cnf decreased also the PhAD amplitude and the number of PhAD per flash when stimulation intensity was above the threshold of behavioural activation. The bf stimulation with 100 cps modulated all investigated parameters differently in their quantity: with 10 cps stimulation VEP amplitude and PhAD trigger rate were differently modulated. Single impulses within the bf 100 ms before flash were ineffective on the evoked potentials. No peak time alterations of the VEP were evoked with 10 cps stimulation within the bf in contrast to Cnf stimulation. The bf seems to be heterogeneous in its physiological effects on the visual cortex.

Animals↗
PubMed1989

Distribution of reduced-nicotinamide-adenine-dinucleotide-phosphate diaphorase-positive cells and fibers in the cat central nervous system.

Previous histochemical studies have suggested that reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase exists in distinct subsets of neurons that neither belong to a single transmitter type nor embrace all the neurons using a single transmitter. As a step toward establishing the role of this enzyme, the distribution of NADPH-diaphorase-positive neurons and fibers in the cat central nervous system was mapped by using a direct histochemical method. Heavily stained NADPH-diaphorase-positive neurons with many prominent cell processes were observed in the cerebral cortex, white matter, caudate nucleus, putamen, nucleus accumbens, septal nucleus, amygdala, anterior, lateral and posterior hypothalamic areas, dorsolateral part of the periaqueductal gray, superior colliculus, central tegmental field (Berman) (pedunculopontine tegmental area), dorsal tegmental nucleus, nucleus coeruleus, mesencephalic and pontine reticular formation, gigantocellular and magnocellular tegmental fields, nucleus facialis, and motor nucleus of the vagus. Moderately stained neurons with two or three prominent cell processes were observed in the nucleus of the diagonal band of Broca, globus pallidus, and substantia innominata. Medium-size, moderately stained neurons that had round large nuclei and no visible cell processes were found in the subthalamic nucleus, pontine gray, trapezoid body, and infratrigeminal, cochlear, and vestibular nuclei. Very dense NADPH-diaphorase-positive nerve terminal fields were seen in the olfactory tubercle, cortex, caudate nucleus, putamen, dentate gyrus, and interpeduncular nucleus. Intensely stained NADPH-diaphorase-positive nerve fibers were found in the stria terminalis, marginal region of the central tegmental field, dorsal tegmental nucleus, and spinal trigeminal tract as well as around the brachium conjunctivum. Although the staining of neurons and tracts was highly selective, they did not correspond to any single known neuronal or neurotransmitter type. Positive staining occurred in discrete subsets of neurons known to be associated with a variety of peptides and classical neurotransmitters. The functional significance of high NADPH diaphorase activity is unknown.

Animals↗
PubMed1996

Representation of olfactory information in the primate orbitofrontal cortex.

1. To analyze the information represented about individual odor stimuli in the responses of single olfactory neurons in the primate orbitofrontal area, neuronal responses were measured to a set of seven to nine odorants in macaques performing an olfactory discrimination task. The population of neurons analyzed had responses that were significantly differential to the odorants. 2. Information theoretic analyses were applied to the responses of the neurons, and information measures were calculated from the firing rate of the responses and from the principal components of the responses. The information reflected by the firing rate of the response accounted for the majority of the information present (86%) when compared with the information derived from the first three principal components of the spike train. This indicated that temporal encoding had a very minor role in the encoding of olfactory information by single orbitofrontal olfactory cells. 3. The average information about which odorant was presented, averaged across the 38 neurons, was 0.09 bits, a figure that is low when compared with the information values previously published for the responses of temporal lobe face-selective neurons. 4. Application of information theoretic analyses to the responses of these neurons showed how much information about which stimulus was delivered was present in the responses of individual neurons. It was found that for the majority of the neurons significant amounts of information were reflected about one or two of the odorants presented. 5. For each neuron, the information reflected in the responses of that neuron about the reinforcement value and the information about the identity of the odorants were calculated. It is shown that many neurons carry information about which of the odorants was presented; in addition, some neurons reflect information only about the taste association of the stimuli and not about odorant identity. 6. Measurements of the sparseness of the representation indicated that a broadly distributed representation of the identity of odorants was present in this population of neurons.

Animals↗
PubMed2006

Synaptic and nonsynaptic localization of GABAA receptors containing the alpha5 subunit in the rat brain.

The alpha5 subunit of the GABA(A) receptors (GABA(A)Rs) has a restricted expression in the brain. Maximum expression of this subunit occurs in the hippocampus, cerebral cortex, and olfactory bulb. Hippocampal pyramidal cells show high expression of alpha5 subunit-containing GABA(A)Rs (alpha5-GABA(A)Rs) both in culture and in the intact brain. A large pool of alpha5-GABA(A)Rs is extrasynaptic and it has been proposed to be involved in the tonic GABAergic inhibition of the hippocampus. Nevertheless, there are no studies on the localization of the alpha5-GABA(A)Rs at the electron microscope (EM) level. By using both immunofluorescence of cultured hippocampal pyramidal cells and EM postembedding immunogold of the intact hippocampus we show that, in addition to the extrasynaptic pool, there is a pool of alpha5-GABA(A)Rs that concentrates at the GABAergic synapses in dendrites of hippocampal pyramidal cells. The results suggest that the synaptic alpha5-GABA(A)Rs might play a role in the phasic GABAergic inhibition of pyramidal neurons in hippocampus and cerebral cortex.

Animals↗
PubMed2004

Neurophysiological effects of corticotropin-releasing factor in living slices of the olfactory area of the rat cortex.

Application of corticotropin-releasing factor (CRF) at concentrations of 10(-9) and 10(-8) M to living brain slices induced activation of the pre- and postsynaptic excitatory components of focal potentials recorded in the slices. The amplitudes and durations of the AMPA and NMDA components of EPSP increased during exposure to CRF, while the amplitude of the GABA(B)-mediated IPSP was suppressed. At the higher CRF concentration (10(-8) M), cells in slices showed epileptiform discharges. The effects of CRF were reversible and disappeared on washing. Long-term treatment with CRF (90 min) induced changes in cells in slices similar to those associated with long-term post-tetanic potentiation. These data provide evidence that CRF has marked activatory properties and influences the glutamatergic and GABAergic systems.

Action Potentials↗
PubMed1987

Behaviour-dependent variability of potentials in the somatosensory cortex evoked by stimulation of the trigeminal nuclei in freely moving rats.

Nine hooded rats with chronically implanted epidural recording electrodes on the right primary somatosensory cortex, the olfactory bulb and bipolar stimulating electrodes in the left ponto-mesencephalic trigeminal nuclei and parabrachial region were investigated during different patterns of spontaneous behaviour. The early positive-negative component of the TNEP with peak times P5 and NII (ms) appeared about 1 ms earlier than after tooth pulp stimulation. The amplitude P5-N11 was slightly increased during drowsiness, decreased during slow wave sleep and was strongly decreased in behavioural patterns with movements, always compared with relaxed wakefulness. The behaviour-dependent changes of cortical EP to stimulation of trigeminal nuclei (TNEP) were analogous to those after tooth pulp stimulation.

Animals↗
PubMed1993

Ornithine decarboxylase is differentially induced by kainic acid during brain development in the rat.

The induction of brain ornithine decarboxylase (ODC) as a consequence of systemic kainic acid administration was studied in the hippocampus and the olfactory cortex-amygdala area of 10-day-old rat pups and 30-day-old young rats. In pups, ODC levels were moderately increased (plus 50-80%) 4 h after kainic acid administration, coming back quickly to control levels afterwards. In young rats, instead, ODC levels were dramatically increased by 17-25-fold, 16 h after kainic acid administration and decreased towards basal levels 48-72 h after injection. The present results suggest that the process of excitotoxic ODC induction can be split in two phases: a first phase characterized by moderate induction and essentially linked to the overstimulation of brain circuits and a second phase, during which a dramatic enzyme stimulation is accompanied by the appearance of neurodegenerative pathology.

Amygdala↗
PubMed1986

Studies on retrograde and anterograde amnesia of olfactory memory after denervation of the hippocampus by entorhinal cortex lesions.

The effect of hippocampal denervation on olfactory memory in rats was tested after interrupting the lateral olfactory tract projections at the level of the entorhinal cortex. When lesioned animals were trained to learn new odors, they showed no evidence of retention 3 h after acquisition. These results confirm earlier data on rapid forgetting in rats after hippocampal deafferentation and are in parallel to the anterograde amnesia typically found in humans with hippocampal damage. On the other hand, preoperatively learned information was minimally impaired after hippocampal deafferentation even if it was acquired within less than 1 h before the lesion. This finding differs from reports on humans as well as monkeys with hippocampal damage where memories formed during a critical time span of months or even years before the lesion are found to be impaired. This may suggest that the consolidation process in humans and rodents has different time scales or that the roles of the human and the rat hippocampal structure in memory formation are somewhat different.

Amnesia↗
PubMed1994

Gustatory, olfactory, and visual convergence within the primate orbitofrontal cortex.

Behavioral and perceptual responses to food depend on a convergence between gustatory, olfactory, and visual information. In previous studies a secondary cortical taste area has been found in the caudolateral orbitofrontal cortex of the primate. Furthermore, neurons with olfactory responses have been recorded in a more medial part of the orbitofrontal cortex, and visual inputs have been shown to influence neurons in an intermediate region. These studies suggest that the orbitofrontal cortex may act as a region for convergence of multiple sensory modalities including chemosensation. In the present study neurons throughout the caudal two-thirds of the orbitofrontal cortex of the macaque were tested to gustatory, to olfactory, and to visual stimulation to investigate whether convergence occurs. Neurons in this region of cortex were found that responded to stimulation of the taste, olfactory, or visual system. In addition, some neurons were found with bimodal responses, responding for example to both taste and olfactory, or taste and visual stimuli. Since these multimodal neurons were found in very close proximity to unimodal neurons, and the unimodal sensory neurons were intermingled, it is possible that the orbitofrontal cortex represents the first cortical area of convergence for these three modalities in primates.

Acoustic Stimulation↗
PubMed2000

Characterization and visualization of [125I] stromal cell-derived factor-1alpha binding to CXCR4 receptors in rat brain and human neuroblastoma cells.

Stromal cell-Derived Factor-1 (SDF-1alpha), binds to the seven-transmembrane G protein-coupled CXCR4 receptor and modulates cell migration, differentiation, and proliferation. CXCR4 has been reported to be expressed in various tissues including brain. Moreover, CXCR4 has recently been shown to be one of the coreceptors for HIV-1 infection which could be implicated in HIV encephalitis. In the present study, the binding properties and autoradiographic distribution of [125I]SDF-1alpha binding to CXCR4 were characterized in the adult rat brain. SDF-1alpha binding and CXCR4 coupling system were also studied in human neuroblastoma cell line SK-N-SH. The binding of [125I]SDF-1alpha on rat brain sections was specific, time-dependent and reversible. The highest densities of CXCR4 were detected in the choroid plexus of the lateral and the dorsal third ventricle. Lower densities of [125I]SDF-1alpha binding sites were observed in various brain regions including cerebral cortex, anterior olfactory nuclei, hippocampal formation, thalamic nuclei, blood vessels and pituitary gland. In the choroid plexus, the IC(50) and K(d) of [125I]SDF-1alpha binding were respectively 0.6 nM and 0. 36 nM. Similar IC(50) values were obtained in other brain structures. A CXCR4 antagonist, bicyclam, competed with SDF-1alpha binding (30% inhibition at 10(-6) M). In SK-N-SH cells, [125I]SDF-1alpha bound to CXCR4 with a K(d) of 5.0 nM and a maximal binding capacity of 460 fmol/mg of protein. SDF-1alpha induced a rapid and transient intracellular calcium increase in SK-N-SH cells. These findings suggest that CXCR4 is highly expressed in some brain structures and have a regulatory role in the nervous system. The significance of this expression in the brain parenchyma and more specifically in the choroid plexus remains to be clarified in the normal as well as in the infected brain.

Animals↗
PubMed1989

Electrical stimulations of the basal forebrain and the nucleus cuneiformis differently modulate behavioural activation of freely moving rat.

Differences in inducing behavioural activation of two different cholinergic brain regions, the basal forebrain (nucleus basalis magnocellularis) and the mesencephalic nucleus cuneiformis were investigated in freely moving rats with electrodes in the hippocampus, the frontal cortex and olfactory bulb. Serial electrical stimulations with increasing intensities, a duration of 1 s and frequencies of 100 and 10 cps and single impulses were applied within both cholinergic regions. After lesions of the stimulated sites the tests were repeated. Serial stimulations of both cholinergic structures increased respiration rate, motor activity, and the trigger rate of slow hippocampal rhythm (theta rhythm) differently. However, the increase of these parameters of behavioural activation by stimulation of the basal forebrain were probably unspecific effects accompanying general behavioural activation because they remained unaffected by lesions of the stimulated sites. The nucleus cuneiformis modulates specifically respiration rate and motor activity. The duration of the behavioural activation by nucleus cuneiformis stimulation was longer compared with basal forebrain stimulation, and it was shortened by lesion of the nucleus cuneiformis. The frequency of the evoked slow hippocampal rhythm was higher with nucleus cuneiformis stimulation. The results indicate that the nucleus cuneiformis is a more homogeneous structure with regard to the modulation of these behavioural parameters whereas the basal forebrain showed more functional heterogeneity with 100 cps stimulation in all investigated parameters, with 10 cps stimulation only in the trigger rate of the slow hippocampal rhythm and the duration of evoked motor activity despite equal effects on the respiration rate and the intensity of motor activity. Functional heterogeneity was also observed in the induction of directed movements whereas with nucleus cuneiformis stimulation the directions of evoked movements were rather equal. Excessive behavioural excitement was only inducible with nucleus cuneiformis stimulation.

Animals↗
PubMed1996

Altered NGF protein levels in different brain areas after immunolesion.

Nerve growth factor (NGF) provides critical trophic support to the cholinergic basal forebrain neurons that express high levels of the low-affinity NGF receptor (p75NGFR) in the adult rat brain. Intraventricular injection of 192 IgG-saporin, made by coupling the monoclonal antibody to p75NGFR 192 IgG to the cytotoxin saporin, selectively destroys the p75NGFR-bearing neurons in the basal forebrain and was used here to examine the effects of selective cholinergic lesions on brain NGF protein levels. We showed that 192 IgG-saporin produced significant long-lasting elevation of NGF protein levels in the hippocampus, cortex, and olfactory bulb, with profound reductions of ChAT activities representing complete cholinergic deafferentations of these areas. NGF level was maintained in the basal forebrain, even though there was almost complete loss of p75NGFR-immunoreactive cells and significant decrease of ChAT activity. In addition, a mild glial response was observed in the basal forebrain, and most of the activated astroglia expressed NGF-like immunoreactivity there. The increases in NGF protein levels in the target areas of the basal forebrain were most likely due to loss of cholinergic basal forebrain neurons and retrograde transport of NGF from these areas. Glial-derived NGF is partially responsible for the maintained level of NGF in the basal forebrain after the loss of cholinergic neurons. The accumulation of NGF protein in the target areas may have some effects on synaptic rearrangement in denervated tissues.

Animals↗