NGF induction of NGF receptor gene expression and cholinergic neuronal hypertrophy within the basal forebrain of the adult rat

Chronic infusion of nerve growth factor (NGF) into the forebrain of the adult rat produced increases in NGF receptor (NGF-R) mRNA hybridization, NGF-R immunoreactivity, choline acetyltransferase (ChAT) mRNA hybridization, and neuronal hypertrophy, when compared with vehicle infusion or noninfused rat brain. In situ hybridization showed NGF induction of NGF-R gene expression, documented by increases in the number of NGF-R mRNA-positive cells within the medial septum, diagonal band, and nucleus basalis magnocellularis. NGF also produced hypertrophy of ChAT mRNA-positive neurons. These results suggest that NGF produces cholinergic neuronal hypertrophy through induction of NGF-R gene expression within the basal forebrain.     

Ciliary neurotrophic factor prevents neuronal degeneration and promotes low affinity NGF receptor expression in the adult rat CNS.

Recombinant human ciliary neurotrophic factor (CNTF) was infused for 2 weeks into the lateral ventricle of fimbria-fornix transected adult rats, and its effects were compared with those of purified mouse nerve growth factor (NGF). We provide evidence that CNTF can prevent degeneration and atrophy of almost all injured medial septum neurons (whereas NGF protects only the cholinergic ones). CNTF is also involved in up-regulation of immunostainable low affinity NGF receptor (LNGFR) in cholinergic medial septum and neostriatal neurons and in a population of lateral septum neurons. In contrast to NGF, CNTF did not stimulate choline acetyltransferase in the lesioned septum and normal neostriatum (pointing to different mechanisms for the regulation of choline acetyltransferase and LNGFR), cause hypertrophy of septal or neostriatal cholinergic neurons, or cause sprouting of LNGFR-positive (cholinergic) septal fibers.     

NGF synthesis and NGF receptor expression in the embryonic mouse trigeminal system

1. The development of the mouse trigeminal system is outlined and its advantages for studying the synthesis of low-abundance regulatory proteins are described. 2. The onset of NGF gene expression and NGF synthesis in the cutaneous target field of the trigeminal ganglion coincide with the arrival of the earliest nerve fibres. 3. The distribution and magnitude of NGF synthesis within the target field are related to its final innervation density. 4. NGF receptors are first detected on trigeminal neurons when their peripheral axons reach the target field. 5. Neither NGF synthesis nor NGF receptor expression are dependent on nerve-target contact but appear to occur as part of an intrinsic developmental program in the target field and neurons, respectively. 6. The time-course of NGF synthesis and NGF receptor expression indicate that NGF does not play a role in guiding axons to their target fields in development.     

Donor- and ligand-dependent differences in C-C chemokine receptor 5 reexpression

N-terminal modifications of the chemokine RANTES bind to C-C chemokine receptor 5 (CCR5) and block human immunodeficiency virus type 1 (HIV-1) infection with greater efficacy than native RANTES. Modified RANTES compounds induce rapid CCR5 internalization and much slower receptor reexpression than native RANTES, suggesting that receptor sequestration is one mode of anti-HIV activity. The rates of CCR5 internalization and reexpression were compared using the potent n-nonanoyl (NNY)-RANTES derivative and CD4(+) T cells derived from donors with different CCR5 gene polymorphisms. NNY-RANTES caused even more rapid receptor internalization and slower reexpression than aminooxypentane (AOP)-RANTES. Polymorphisms in the promoter and coding regions of CCR5 significantly affected the receptor reexpression rate after exposure of cells to NNY-RANTES. These observations may be relevant for understanding the protective effects of different CCR5 genotypes against HIV-1 disease progression.     

Augmentation of cholinergic activity of the neostriatum alters established type of motor behaviour in animals

Bilateral microinjections of carbacholine into dorsolateral portion of the caudate nucleus head reduced a phasic component, augmented a tonic component of instrumental response, inhibited interstimuluv raisings, normalised posture, and calmed down the dogs under study. They also improved differentiation of meaningful signals. Microinjections of scopolamine into the striatum induced opposite effects. Bilateral injections provided a longer lasting effect on both motor and sensory components of instrumental responses.     

Structure and developmental expression of the chicken NGF receptor

The nucleotide and deduced amino acid sequence of a cDNA clone of the chicken NGF receptor (NGFR) is reported and is compared with sequences of mammalian NGF receptors. A model is presented in which monodentate or bidentate binding of NGF dimers to repeated cysteine-rich sequence elements of the receptor yields low- or high-affinity NGF binding, respectively. In situ hybridization is used to characterize expression of NGFR in developing chick from 40 hr to 10 days of embryogenesis. NGFR mRNA expression is detected in premigratory neural crest cells, in epibranchial placode cells, and in all sensory, sympathetic and parasympathetic derivatives of these structures. In the embryonic CNS, NGFR mRNA is detected in the mantle zone but not the periventricular germinal zone throughout most of the neural tube. By Embryonic Day 8, NGFR mRNA is detected in a substantial fraction of cells in every brain region, with highest levels present in developing motor neurons. NGFR mRNA also is transiently expressed in many mesenchymal cell populations including cells in branchial arch, sclerotome, muscle anlagen, and feather follicles. The functional significance of wide-spread embryonic expression of the NGF receptor is discussed.     

Distribution of cholinergic neuronal differentiation factor/leukemia inhibitory factor binding sites in the developing and adult rat nervous system in vivo

Cholinergic neuronal differentiation factor/leukemia inhibitory factor (CDF/LIF) is a multi-functional cytokine that affects neurons as well as many other cell types. Toward elucidating its neural functions in vivo, we previously investigated the distribution of CDF/LIF binding sites with iodinated native CDF/LIF in embryonic to postnatal day 0 (P0) rats. In the present study, we have extended our examination to postnatal ages and find that specific CDF/LIF binding sites are present at defined developmental stages in additional brain regions not previously exhibiting binding by P0. High levels of binding are detected in all P7 sensory and autonomic ganglia examined, but only in restricted postnatal central nervous system structures. Cranial motor and mesencephalic trigeminal neurons maintain high levels throughout, while binding to spinal motor neurons, which decreases to low levels at P0, reappears by P14 and increases with age. Most other structures, which show detectable binding by P0, exhibit higher levels at postnatal ages, including the red, deep, ventral cochlear, trapezoid, superior olivary, vestibular, ventral tegmental, and ventral posterior thalamic nuclei as well as the glomerular layer of the olfactory bulb. High levels are also detected in several structures for the first time after P0, including the cerebellar cortex (molecular and Purkinje cell layers), lateral reticular nucleus of the medulla and reticular formation, as well as the reticulotegmental, medial geniculate, solitary (rostral, dorsomedial, and commissural regions), medial septal, lateral mammillary, and lateral habenular nuclei. These results not only identify regions of potential CDF/LIF-responsive neurons and glia throughout development but suggest new CDF/LIF roles in the nervous system. © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 163–192, 1997.     

Comparative study of the neuronal structure of the neostriatum in birds with different extrapolation capabilities

A comparative study of the neuronal structure of neostriatum in crows possessing a great capacity for extrapolation of the movement direction of an alimentary stimulus, and in pigeons deprived of it, did not reveal any fundamental differences in the size of cells, the number of dendritic endings and dendritic ramifications. Differences were observed in the neuronal morphology. In the crow neostriatum neurones, the dendrites are thinner, more sinous and provided with a denser cover of extremely fine protoplasmatic protrusions. In corresponding pigeon neurones the dendrites are thicker, more straight and with a smaller number of rather large protoplasmatic outgrowths. Such differences apparently set up morphological prerequisites for a finer analysis and processing of information, which may contribute to greater capacity of crows for extrapolation.     

Role of cAMP in dopamine effect on background and glutamate-induced neuronal activity in rat neostriatum

During acute experiments on rats immobilized with d-tubocurarine, the effects were compared of microiontophoretically applied dopamine and dibutyryl cAMP on background and glutamate-induced spike activity of neostriatalneurons. The algorithm of the analysis of extracellularly recorded spike activity included the plotting of a graph of mean frequency, assessing its stationarity, and producing histograms of interspike intervals and also correlation function. During these experiments it was shown that dibutyryl cAMP imitates the inhibitory but not the activating effect of dopamine on the spontaneous and glutamate-induced spike activity of neostriatal neurons.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka, Moscow Province. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 614–619, September–October, 1985.     

Neurogenesis and neuronal regeneration in the adult fish brain

Fish are distinctive in their enormous potential to continuously produce new neurons in the adult brain, whereas in mammals adult neurogenesis is restricted to the olfactory bulb and the hippocampus. In fish new neurons are not only generated in structures homologous to those two regions, but also in dozens of other brain areas. In some regions of the fish brain, such as the optic tectum, the new cells remain near the proliferation zones in the course of their further development. In others, as in most subdivisions of the cerebellum, they migrate, often guided by radial glial fibers, to specific target areas. Approximately 50% of the young cells undergo apoptotic cell death, whereas the others survive for the rest of the fish’s life. A large number of the surviving cells differentiate into neurons. Two key factors enabling highly efficient brain repair in fish after injuries involve the elimination of damaged cells by apoptosis (instead of necrosis, the dominant type of cell death in mammals) and the replacement of cells lost to injury by newly generated ones. Proteome analysis has suggested well over 100 proteins, including two dozen identified ones, to be involved in the individual steps of this phenomenon of neuronal regeneration.     

Expression of neuronal-NOS in developing basal forebrain cholinergic neurons: Regulation by NGF

Nerve growth factor (NGF) acts through the receptor tyrosine kinase trkA to serve as a trophic factor for cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band. We have previously shown that the neuronal isoform of nitric oxide synthase (NOS) is selectively expressed in a large fraction of trkA-expressing cholinergic neurons in these brain regions in the adult rat, and that NGF induces the expression of neuronal-NOS in these cells. Herein, we show that: 1) neuronal-NOS is also localized to these neurons in the developing septum; 2) the expression of neuronal-NOS is regulated in the developing medial septal nucleus and vertical limb of the diagonal band; 3) neuronal-NOS regulation parallels that for other markers of basal forebrain cholinergic neuron differentiation, such as cholineacetyltransferase; and 4) NGF infusion in the postnatal period induces robust increases in neuronal-NOS mRNA and in NOS activity in the basal forebrain. Taken together with earlier findings, our results suggest that neuronal-NOS has a role in the differentiation and mature function of septal cholinergic neurons. Through enhancing neuronal-NOS synthesis, endogenous NGF is likely to regulate NO functions in vivo. Special issue dedicated to Dr. Hans Thoenen.     

Intrahippocampal injection of NGF accelerates spontaneous alteration ontogenesis and the maturation of septohippocampal cholinergic innervation in rats

A single intrahippocampal injection of nerve growth factor (NGF), performed on postnatal (PND) 8 or 13, accelerated the development of spontaneous alternation in rats. This precocity was of approximately 5 days, appearing on the 4th day after the treatment and persisting through to the end of the development (PND 40). Combined microinjections of NGF and an antimuscarinic (atropine) or an antinicotinic (mecamylamine) substance have indicated that NGF probably acts through accelerating the development of the septo-hippocampal cholinergic fibers involved in this behavior.     

Effects of NGF and glucocorticoid on NGF receptor immunolabeling of cultured rhesus adrenal chromaffin cells

Nerve growth factor (NGF) promotes the outgrowth of neurites from cultured adrenal chromaffin cells from adult rhesus monkeys, but little is known about the distribution, at the cellular level, of the NGF receptors (NGFR) responsible for this response. We examined changes in immunostaining for NGFR in chromaffin cells cultured for 4 weeks in the presence or absence of NGF, with or without dexamethasone (DEX), which inhibits neuritic outgrowth from these cells. Purified cultures of adrenal chromaffin cells from adult rhesus monkeys were grown for up to 9 weeks in NGF, DEX, NGF plus DEX, or control medium. Cells were immunolabeled with three different monoclonal antibodies directed against different epitopes of the human NGFR. Although the distribution of immunolabeling was not uniform from cell to cell, the overall intensity of NGFR immunolabeling varied dramatically between different growth conditions. Of greatest interest, DEX-treated cells stained the most intensely at all time points, while the intensity of immunolabeling was much fainter in NGF-treated cells and decreased with time in culture. In contrast to the intensity of labeling, the proportion of chromaffin cells with immunoreactivity increased with time in all treatment groups. Thus, GCs do not appear to antagonize the effects of NGF merely by decreasing the total number of immunoreactive NGFR on the surface of these cells.     

Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds

In the high vocal center (HVC) of adult songbirds, increases in spontaneous neuronal replacement correlate with song changes and with cell death. We experimentally induced death of specific HVC neuron types in adult male zebra finches using targeted photolysis. Induced death of a projection neuron type that normally turns over resulted in compensatory replacement of the same type. Induced death of the normally nonreplaced type did not stimulate their replacement. In juveniles, death of the latter type increased recruitment of the replaceable kind. We infer that neuronal death regulates the recruitment of replaceable neurons. Song deteriorated in some birds only after elimination of replaceable neurons. Behavioral deficits were transient and followed by variable degrees of recovery. This raises the possibility that induced neuronal replacement can restore a learned behavior.