NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum

Gage, Fred H.; Batchelor, Peter; Chen, Karen S.; Chin, Donna; Higgins, Gerald A.; Koh, Sookyong; Rosenberg, Michael B.; Fischer, Walter; Björklund, Anders

doi:10.1016/0896-6273(89)90184-0

Cited by 242 publications

(85 citation statements)

References 31 publications

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“…NGF and its mRNA content in the hippocampus are reported to be decreased in aged (28 months old) rats [47]. Moreover, LNGFRLIS was shown to be induced by NGF [48]. The present results are consistent with these findings.…”

Section: Discussionsupporting

confidence: 82%

Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Asada

Nonomura

Nakagawa

1992

J. Clin. Biochem. Nutr.

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Summaryin mammals, the hypothalamic suprachiasmatic nucleus (SCN ), a circadian oscillator, receives the retinohypothalamic tract (RHT), which is essential for the synchronization of circadian rhythms by light-dark cycle; and nerve growth factor (NGF) receptors with low affinity have been detected in the SCN. Thus, we examined whether low-affinity NGF receptors (LNGFR) are present in the terminals of the RHT by studies on the LNGFR-like immunoreactive substance (LNGFRLIS) in the SCN of blind rats. LNGFRLIS in the SCN gradually decreased with age in control rats, though it could be observed until 16-20 weeks of age. After bilateral orbital enucleation of 4-week-old rats, the density of the LNGFRLIS gradually decreased on both sides of the SCN from week 4 after the operation, disappearing 7 weeks after the operation. In congenitally blind, hereditary microphthalmic rats, LNGFRLIS was not detectable in the SCN, but in half-blind hereditary microphthalmic rats LNGFRLIS was detectable on both sides of the SCN. 125I-NGF injected into the SCN was found in the optic nerve and the retina. Since NGF is suggested to be retrogradely transported and to support survival of neurons, these findings suggest that LNGFR is present at the terminal of the RHT, and raise the possibility that NGF or other growth factors such as brain-derived neurotrophic factor in or around the SCN plays a role in maintaining the retinal ganglion cells through LNGFR.

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Section: Discussionsupporting

confidence: 82%

Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Asada

Nonomura

Nakagawa

1992

J. Clin. Biochem. Nutr.

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“…Thus, transection of septal cholinergic neuron projections to the hippocampus prevents target-derived nerve growth factor (NGF) signaling and leads to neuronal atrophy and loss of characteristic markers of cholinergic phenotype without cell death (30,31). On the other hand, NGF infusion in the striatum of adult animals can protect or stimulate the cholinergic phenotype of interneurons (32)(33)(34). However, these studies have not determined whether upon withdrawal of neurotrophin signaling cholinergic neurons adopt an alternative neuronal identity.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum

Lopes

Wijk

Neves

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The generation and maintenance of a plethora of neuronal subtypes is essential for normal brain function. Nevertheless, little is known about the molecular mechanisms that maintain the defining characteristics of neurons following their initial postmitotic specification. Using conditional gene ablation in mice, we demonstrate here that the homeodomain protein LIM homeobox (Lhx)7 is essential for maintaining the morphological and molecular characteristics of cholinergic interneurons of the striatum. Lhx7-depleted cholinergic interneurons extinguish expression of several subtype-specific markers, including choline acetyl transferase and Isl1, and are respecified into Lhx6-expressing mature GABAergic interneurons. Additional expression studies support a model where Lhx7 controls the choice between cholinergic or GABAergic identity by gating a cross inhibitory regulation between Isl1 and Lhx6. By demonstrating that the switch between alternative striatal interneuron fates depends on persistent activity of a single transcription factor, we provide evidence that the intrinsic plasticity of mammalian forebrain neuronal subtypes is maintained after the initial specification and lineage commitment and possibly throughout life.neuronal subtype specification | medial ganglionic eminence-derived interneurons T he information-processing ability of the nervous system depends on the formation of functional neuronal circuits composed of a highly heterogeneous population of neurons. Recent progress has identified molecular cascades that control the generation of distinct neuronal subtypes during development (1-3) but the mechanisms that maintain the identity of neurons following lineage commitment and differentiation are currently unclear. Identifying such mechanisms is critical for understanding phenotypic plasticity in the nervous system and, ultimately, influencing its ability to adjust during normal development, disease, or injury.The striatum is a subcortical structure that integrates multiple inputs from the cortex, thalamus, and midbrain and relays information to the output domains of the basal ganglia via its principal population of projection neurons (4, 5). Balanced striatal output, which is critical for motor and cognitive activity, depends on local circuits controlled by distinct subpopulations of GABAergic and cholinergic interneurons (5). Both GABAergic and cholinergic striatal interneurons (GSIs and CSIs, respectively) are derived from Nkx2.1-expressing progenitors of the medial ganglionic eminence (MGE) (6, 7), which, upon exit from the cell cycle, express the LIM homeodomain (LIM HD) transcription factors LIM homeobox 6 (Lhx6) and LIM homeobox 7 (Lhx7) (8). A subset of these precursors maintains expression of Lhx6 and differentiate into mature GABAergic interneurons expressing the neuropeptide somatostatin (Sst) or the calcium-binding protein parvalbumin (Pv) (9, 10). The remaining precursors induce expression of the LIM HD protein Isl1, down-regulate Lhx6, and differentiate into CSIs (8). In adult animals, all ...

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“…Proximity to the lateral ventricles may affect penetration of the toxin and hence loss of ChAT activity in a specific region (Schweitzer 1987;Waite et al 1995); however, differences in ChAT losses between neocortex and amygdala or entorhinalpiriform cortex are more difficult to reconcile on the basis of simple accessibility of the toxin to these structures. Immunohistochemical work in rats and humans has demonstrated that, although the p75 receptor is found on cholinergic cells, not all cholinergic neurons carry p75 (Gage et al 1989;Yan and Johnson 1989;Heckers et al 1994;Rossner et al 1995b). In particular, ChAT-positive, p75-negative neurons have been reported in the nucleus basalis-substantia innominata complex, whose fibers have been surmised to project to the amygdala and parts of the rhinal paralimbic areas (Heckers et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Holschneider

Waite

Leuchter

et al. 1999

Experimental Brain Research

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Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 μg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%-84%) and hippocampus (93%), with relative sparing of entorhinalpiriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1-to 4-Hz power, decreases in 20-to 44-Hz power, and decreases in 4-to 8-Hz intraand interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial

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NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum

Cited by 242 publications

References 31 publications

Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

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