Morphogenic Role for Acetylcholinesterase in Axonal Outgrowth during Neural Development

Abstract

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

Exposure to Diazinon Alters In Vitro Retinogenesis: Retinospheroid Morphology, Development of Chicken Retinal Cell Types, and Gene Expression

“…It is described that AChE typically appears during neural development while axons are growing and before synaptic connections form (for review see Layer, 1991). This transient AChE expression is no accident of development, but is correlated with an AChE role of promoting axonal outgrowth or synaptic connection (Anderson and Key, 1999;Bigbee et al, 1999Bigbee et al, , 2000. The present study established that both amacrine cells and ganglion cells were affected by diazinon in their numbers and distribution.…”

“…All organophosphorus compounds have a mechanism of toxicity in common, that is, phosphorylation of AChE causing accumulation of acetylcholine, overstimulation of cholinergic receptors, and consequently, signs of cholinergic toxicity. On the other hand, organophosphate exposures have also been shown to downregulate muscarinic receptors, inhibit the adenylate cyclase signaling cascade, decrease brain DNA and RNA synthesis, and suppress neurite outgrowth and cell adhesion (Anderson and Key, 1999;Bigbee et al, 1999;Dam et al, 1998;Lein and Fryer, 2005;Li and Casida, 1998;Song et al, 1997). Therefore, developmental exposures may be more dangerous than previously thought, both because acetylcholinesterase may have a direct role on neuronal differentiation, and moreover, the organophosphorus compounds also act on other components of the cholinergic system.…”

Developmental Chlorpyrifos and Methyl Parathion Exposure Alters Radial-Arm Maze Performance in Juvenile and Adult Rats

“…They do suggest that developmental OP exposure has the potential to disrupt synaptic function, and this disruption is present during the period where we observed behavioral alterations. It has been previously suggested that OP exposure may change neuronal connectivity in the developing brain which could result in aberrant behavioral outcomes (Bigbee et al, 1999;Brimijoin and Koenigsberger, 1999).…”

Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior

“…These findings suggest that developmental neurotoxicity is mediated by mechanisms other than those implicated in acute OP neurotoxicity (Abou-Donia, 2003;Costa, 2006;Ecobichon, 1994). It is postulated that the neurobehavioral deficits associated with developmental CPF exposure reflect altered neuronal connectivity in the developing brain (Bigbee et al, 1999;Brimijoin and Koenigsberger, 1999;Slotkin, 2004a).…”