Neurotrophin‐4/5 Maintains the Cholinergic Phenotype of Axotomized Septal Neurons

Alderson, RF; Sj, Wiegand; Kd, Anderson; Cai, Ning; Cho, Joo Youn; Lindsay, R. M.; Ca, Altar

doi:10.1111/j.1460-9568.1996.tb01212.x

Cited by 29 publications

(15 citation statements)

References 50 publications

(55 reference statements)

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“…NT4 is supplied to thalamic neurons by layer IV and VI target neurons or with anterograde delivery by layer VI corticothalamic projections. Besides, the TrkB ligands may also serve other afferent systems, because, for instance, basal forebrain and noradrenergic projections express TrkB receptors (Alderson et al ., 1996).…”

Section: Discussionmentioning

confidence: 99%

Developmental changes of neurotrophin mRNA expression in the layers of rat visual cortex

Patz

Wahle

2006

Eur J of Neuroscience

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Neurotrophins are essential factors for the structural, neurochemical and functional maturation of the brain including developmental and adult plasticity. Northern blots and polymerase chain reaction revealed the expression of neurotrophin 4 (NT4), neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the cortex. The cellular producers of NT3 and BDNF have been characterized by anatomical methods as being mostly pyramidal, and the tyrosine kinase B (TrkB) receptor is expressed by many cortical neurons. However, these methods have so far failed to identify the cells producing NT4 and NGF mRNA. These factors are much lower in expression than, e.g. BDNF, and apparently remain below detection levels of in situ hybridization. Given their specific actions on cell types and afferent systems, knowledge about the producing cell types is highly desirable. To narrow down on the producing cell types, we quantified by reverse transcriptase-polymerase chain reaction (RT-PCR) the developmental changes of BDNF, NT3, NT4, NGF and TrkB mRNA expression in total visual cortex lysates, and in the cortical layers dissected by tangential cryostat sectioning. We found dramatic changes in laminar expression of NT3 and NGF, mild changes of NT4, and no changes of BDNF and TrkB mRNA. For instance, NT3 is important early on for thalamocortical axons, and we found transient peaks of NT3 mRNA expression first in layer VI, then in layer IV. NT4 mRNA was in layers IV and VI, suggesting NT4 protein production in thalamorecipient layers, but peak expression gradually shifted to upper layers as did NGF expression. The layer-specific developmental expression shifts of neurotrophin mRNAs correlate with morphogenetic processes.

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Section: Discussionmentioning

confidence: 99%

Developmental changes of neurotrophin mRNA expression in the layers of rat visual cortex

Patz

Wahle

2006

Eur J of Neuroscience

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“…The effects of other exogenously applied neurotrophic factors on the number of ChAT-immunoreactive neurons following fimbriafornix transection have been described in the literature (e.g. Anderson et al, 1988;Otto et al, 1989;Hagg et al, 1992;Knusel et al, 1992;Alderson et al, 1996).…”

Section: Ngf Immunoreactivity and Ngf Receptor Expression In Medial Smentioning

confidence: 99%

Recovery of ChAT lmmunoreactivity in Axotomized Rat Cholinergic Septal Neurons Despite Reduced NGF Receptor Expression

Naumann

Straube

Frotscher

1997

Eur J of Neuroscience

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Previous studies have suggested that target-derived nerve growth factor (NGF) is essential for the survival of cholinergic basal forebrain neurons. Thus, axotomy of septohippocampal neurons in adult rats resulting in the withdrawal of target-derived NGF caused a dramatic loss of choline acetyltransferase (ChAT)-immunoreactive neurons in the medial septum-diagonal band complex. We have recently shown that this loss of immunolabelled neurons does not indicate cell death, since many septohippocampal cholinergic neurons recover their immunoreactivity for ChAT after a long survival time despite disconnection from target-derived neurotrophins. One possibility would be that these surviving ChAT-immunoreactive neurons have gained access to other, probably local, NGF sources. Here we provide evidence that the recovery of ChAT immunoreactivity after axotomy is not accompanied by a similar recovery of NGF receptor expression in these neurons. In situ hybridization for p75NTR mRNA and trkA mRNA 6 months after bilateral fimbria-fornix transection revealed a substantial loss of labelled cells. In addition, there was a persisting loss of p75NTR-immunoreactive and NGF-immunoreactive medial septal neurons. Cholinergic neurons in controls did not express NGF mRNA, but were heavily immunostained for NGF protein due to receptor-mediated uptake. These data suggest that at least some cholinergic septohippocampal neurons re-express ChAT either independently of NGF or with a reduced need for NGF.

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“…Choline acetyltransferase (ChAT) is the enzyme responsible for the synthesis of acetylcholine. ChAT activity and acetylcholine release in vitro and in vivo are known to be promoted by several trophic factors, including nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), and fibroblast growth factor (FGF; Grothe et al, 1989; Alderson et al, 1990, 1996; Rylett and Williams, 1994; Yokoyama et al, 1994; Nonner et al, 2000; Burgess and Aubert, 2006).…”

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confidence: 99%

Stimulation of choline acetyltransferase by C3d, a neural cell adhesion molecule ligand

Burgess

Saini

Weng

et al. 2008

J of Neuroscience Research

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Septal cholinergic neurons project to the hippocampus and release acetylcholine, a neurotransmitter involved in learning and memory. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing acetylcholine. Promoting ChAT activity and acetylcholine release can lead to new treatments for neurodegenerative diseases with cholinergic deficits, such as Alzheimer's disease. We present evidence that the synthetic molecule C3d, which is a peptide mimetic of the neural cell adhesion molecule (NCAM), promotes ChAT activity in cultures of rat embryonic septal neurons. Our data demonstrate that ChAT activity triggered by C3d is dependent on the fibroblast growth factor receptor (FGFR) and the mitogen-activated protein kinase (MAPK) pathway. C3d did not affect the number of cholinergic neurons in culture, indicating that NCAM homophilic binding enhances ChAT activity, without affecting cholinergic cell survival. In conclusion, the NCAM mimetic peptide C3d promotes ChAT activity in septal neurons through FGFR and MAPK. These findings are relevant to the design of new strategies aimed at stimulating cholinergic function and improving cognition in disorders such as Alzheimer's disease.

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Neurotrophin‐4/5 Maintains the Cholinergic Phenotype of Axotomized Septal Neurons

Cited by 29 publications

References 50 publications

Developmental changes of neurotrophin mRNA expression in the layers of rat visual cortex

Developmental changes of neurotrophin mRNA expression in the layers of rat visual cortex

Recovery of ChAT lmmunoreactivity in Axotomized Rat Cholinergic Septal Neurons Despite Reduced NGF Receptor Expression

Stimulation of choline acetyltransferase by C3d, a neural cell adhesion molecule ligand

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