The effect of acetylcholinesterase on outgrowth of dopaminergic neurons in organotypic slice culture of rat mid-brain

Jones, Sarah; Holmes, Catherine; Budd, T. C.; Greenfield, Susan A.

doi:10.1007/s004410050287

Cited by 14 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, treatment of cultured DRG neurons with certain AChE inhibitors produces a dose-dependent, but reversible, reduction in outgrowth that is accompanied by an abnormal accumulation of neurofilaments in the cell body Bigbee, 1994, 1996;Dupree et al, 1995). Similar effects on outgrowth have also been obtained for chick tectal and retinal ganglion neurons (Layer et al, 1993), sympathetic ganglion neurons (Small et al, 1995), dopaminergic midbrain neurons (Jones et al, 1995), and Aplysia pedal ganglion neurons (Srivatsan and Peretz, 1997). However, it is important to note that not all AChE inhibitors share the ability to affect neurite outgrowth, i.e., some compounds that inhibit AChE activity do not interfere with neurite outgrowth (Layer et al, 1993;Jones et al, 1995;Small et al, 1995;Srivatsan and Peretz, 1997).…”

Section: Introductionmentioning

confidence: 61%

Acetylcholinesterase antibody treatment results in neurite detachment and reduced outgrowth from cultured neurons: Further evidence for a cell adhesive role for neuronal acetylcholinesterase

Sharma

Bigbee

1998

J. Neurosci. Res.

View full text Add to dashboard Cite

Data from our laboratory and others demonstrate that acetylcholinesterase (AChE) is expressed transiently by neurons during periods of neurite outgrowth preceding synaptogenesis, suggesting an extrasynaptic function for this molecule. These findings, along with reports that AChE shares amino acid sequence homology and structural similarities with known cell adhesion molecules, have led to the theory that, during development, AChE may exert a morphogenic effect through cell adhesion. To further test this hypothesis, we have examined the effects of an AChE monoclonal antibody (MAB304) on neurite outgrowth in primary cultures of rat dorsal root ganglion (DRG) neurons. Short-term, high-concentration antibody treatment produced a rapid detachment of established DRG neurites, which was followed by regrowth upon removal of the antibody from the culture medium. This effect appeared to be site-specific, because other AChE antibodies that were able to detect AChE immunocytochemically failed to produce this disadhesion. Long-term, low-concentration antibody exposure produced a 50% reduction in total area of outgrowth, in which neurites were more densely packed and interlaced compared with the neurites in control cultures. These results extend our previous observations on the outgrowth perturbing effects of AChE inhibitor treatment and provide further evidence that AChE may support neurite outgrowth through a cell adhesive role.

show abstract

Section: Introductionmentioning

confidence: 61%

Acetylcholinesterase antibody treatment results in neurite detachment and reduced outgrowth from cultured neurons: Further evidence for a cell adhesive role for neuronal acetylcholinesterase

Sharma

Bigbee

1998

J. Neurosci. Res.

View full text Add to dashboard Cite

show abstract

“…However, it is important to note that the observed effects of AChE inhibitors on neurite outgrowth are independent of the ability of these compounds to inhibit esteratic activity. For example, we and others (20,28,29) have shown that irreversible inhibition of AChE with the organophosphate diisopropylflurophosphate (DFP) has no effect on neurite outgrowth from either CNS or PNS neurons. These studies indicate that the catalytic activity of AChE is not required for its Days in vitro 6 7 Figure 1.…”

Section: Parmacologic Inhibitor Treatmentmentioning

confidence: 99%

“…Other in vitro studies employing a variety of neuronal cell types have reported retardation of neurite outgrowth in response to AChE inhibitor treatment. These studies used chick tectal and retinal ganglion neurons (30), rat sympathetic ganglion neurons (28), dopaminergic midbrain neurons (29), spinal motor neurons (38), and Aplysia pedal ganglion neurons (39). These studies show that the most potent inhibitor of outgrowth was BW284c5 1, which occupies both the catalytic and the peripheral anionic sites of the active center gorge ofAChE.…”

Section: Parmacologic Inhibitor Treatmentmentioning

confidence: 99%

Morphogenic Role for Acetylcholinesterase in Axonal Outgrowth during Neural Development

Bigbee¹,

Sharma²,

Gupta³

et al. 1999

Environmental Health Perspectives

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) is the enzyme that hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses and neuromuscular junctions. However, results from our laboratory and others indicate that AChE has an extrasynaptic, noncholinergic role during neural development. This article is a review of our findings demonstrating the morphogenic role of AChE, using a neuronal cell culture model. We also discuss how these data suggest that AChE has a cell adhesive function during neural development. These results could have additional significance as AChE is the target enzyme of agricultural organophosphate and carbamate pesticides as well as the commonly used household organophosphate chlorpyrifos (Dursban). Prenatal exposure to these agents could have adverse effects on neural development by interfering with the morphogenic function of AChE. -Environ Health Perspect 107(Suppl 1): 81-87 (1999). http.//ehpnetl.niehs.nih.gov/docs/1999/Suppl-1/81-B7bigbee/abstract.html

show abstract

“…A number of different groups have reported that AChE promotes neurite growth [93][94][95][96][97]. Although this could depend in part on acetylcholine hydrolysis, this effect has also been reported with an inactive form of AChE [97].…”

Section: C-terminal Peptides and Nonclassical Functions Of Cholinestementioning

confidence: 96%

The Origin of the Molecular Diversity and Functional Anchoring of Cholinesterases

Massoulié¹

2002

Neurosignals

252

209

View full text Add to dashboard Cite

Vertebrates possess two cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which both hydrolyze acetylcholine, but differ in their specificity towards other substrates, and in their sensitivity to inhibitors. In mammals, the AChE gene produces three types of coding regions through the choice of 3′ splice acceptor sites, generating proteins which possess the same catalytic domain, associated with distinct C-terminal peptides. AChE subunits of type R (‘readthrough’) produce soluble monomers; they are expressed during development and induced by stress in the mouse brain. AChE subunits of type H (‘hydrophobic’) produce GPI-anchored dimers, but also secreted molecules; they are mostly expressed in blood cells. Subunits of type T (‘tailed’) exist for both AChE and BChE. They represent the enzyme forms expressed in brain and muscle. These subunits generate a variety of quaternary structures, including homomeric oligomers (monomers, dimers, tetramers), as well as hetero-oligomeric assemblies with anchoring proteins, ColQ and PRiMA. Mutations in the four-helix bundle (FHB) zone of the catalytic domain indicate that subunits of type H and T use the same interaction for dimerization. On the other hand, the C-terminal T peptide is necessary for tetramerization. Four T peptides, organized as amphiphilic α helices, can assemble around proline-rich motifs of ColQ or PRiMA. The association of AChE_T or BChE subunits with ColQ produces collagen-tailed molecules, which are inserted in the extracellular matrix, e.g. in the basal lamina of neuromuscular junctions. Their association with PRiMA produces membrane-bound tetramers which constitute the predominant form of cholinesterases in the mammalian brain; in muscles, the level of PRiMA-anchored tetramers is regulated by exercise, but their functional significance remains unknown. In brain and muscles, the hydrolysis of acetylcholine by cholinesterases, in different contexts, and their possible noncatalytic functions clearly depend on their localization by ColQ or PRiMA.

show abstract

The effect of acetylcholinesterase on outgrowth of dopaminergic neurons in organotypic slice culture of rat mid-brain

Cited by 14 publications

References 0 publications

Acetylcholinesterase antibody treatment results in neurite detachment and reduced outgrowth from cultured neurons: Further evidence for a cell adhesive role for neuronal acetylcholinesterase

Acetylcholinesterase antibody treatment results in neurite detachment and reduced outgrowth from cultured neurons: Further evidence for a cell adhesive role for neuronal acetylcholinesterase

Morphogenic Role for Acetylcholinesterase in Axonal Outgrowth during Neural Development

The Origin of the Molecular Diversity and Functional Anchoring of Cholinesterases

Contact Info

Product

Resources

About