Morphogenetic roles of acetylcholine.

Abstract

In the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits. In developing tissues and primitive organisms, neurotransmitters subserve growth regulatory and morphogenetic functions. Accumulated evidence suggests that acetylcholine, (ACh), released from growing axons, regulates growth, differentiation, and plasticity of developing central nervous system neurons. In addition to intrinsic cholinergic neurons, the cerebral cortex and hippocampus receive extensive innervation from cholinergic neurons in the basal forebrain, beginning prenatally and continuing throughout the period of active growth and synaptogenesis. Acute exposure to ethanol in early gestation (which prevents formation of basal forebrain cholinergic neurons) or neonatal lesioning of basal forebrain cholinergic neurons, significantly compromises cortical development and produces persistent impairment of cognitive functions. Neonatal visual deprivation alters developmental expression of muscarinic acetylcholine receptors (mAChR) in visual cortex, whereas local infusion of mAChR antagonists impairs plasticity of visual cortical neurons. These findings raise the possibility that exposure to environmental neurotoxins that affect cholinergic systems may seriously compromise brain development and have long-lasting morphologic, neurochemical, and functional consequences.-Environ Health Perspect 107(Suppl 1): 65-69 (1999). http.//ehpnet1.niehs.nih.gov/docs/1999/ Suppl-1/65-691auder/abstract. html

Magnetic resonance spectroscopy outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders

“…During brain development, cholinergic neurons project from the nucleus basilis of Meynert to the frontal lobe [42]. Lauder and Schambra [64] reported that prenatal ethanol exposure in the mouse led to severely affected development of the forebrain CNS cholinergic system with deleterious effects on the synaptic targets of these cholinergic neurons, including reduced thickness of the cerebral cortex. The frontal lobe was significantly smaller (relative and absolute) in FAS/PFAS relative to all other groups (Fig.…”

“…Early work by Sulik and Johnston [70,71], Sulik [72], Schambra et al [23] and Lauder and Schambra [64] illustrated the teratogenic impact of alcohol on the developing cholinergic system. As reported by Lauder and Schambra [64], in the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits.…”

Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children

“…Organophosphates (OPs) and carbamates break down the enzyme acetylcholinesterase (AChE), already lower during pregnancy (Evans et al 1988), allowing acetylycholine to build up in the neuronal junction. AChE inhibition disrupts cell replication and differentiation, synap-togenesis, and axonogenesis (Bigbee et al 2000; Lauder and Schambra 1999). It is likely that pesticides also act through noncholinergic mechanisms involving alterations in expression and function of nuclear transcription factors (Dam et al 2003).…”

Neurobehavioral effects of choninergic drugs in prenatal period

“…Эти гомеостатические механизмы вовлекают из-менения и пресинаптические и постсинаптиче-ские компоненты холинергической системы, вклю-чая высокое сродство к транспортеру холина, АХ-трансферазе и mАХ [58,148]. Многие из выше-упомянутых компенсационных механизмов участву-ют в процессе нервного развития и могут привести к нейроповеденческим отклонениям у развиваю-щихся животных [51, 63,103,106,107].…”