The Cholinergic System in Developing Cerebellum: Comparative Study of Normal, Hypothyroid and Underfed Rats

Abstract

To overcome the deficiencies of previous findings, the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were studied at very short age intervals to allow a more precise definition of the shape and timing of their developmental curves in normal, hypothyroid and underfed rats. In addition, AchE expression in developing cerebellum was studied histochemically in these three neurological models. When compared with structural findings in the literature, the results provide the following information on the normal and abnormal developing cholinergic system, related or not to cerebellar neurotransmission (1) AchE activity, unlike ChAT, can be considered as a good marker of the developing cholinergic archicerebellum. (2) ChAT and AchE are transiently expressed together in functionally noncholinergic Purkinje cells. In contrast with most regions of the central nervous system, the high ratio of ChAT to AchE activities in the early stage of cerebellar development suggests an enhanced synthesis of acetylcholine (Ach). The level of ChAT activity correlates with Purkinje cell size, supporting the concept of a neurotrophic role of Ach in early maturing macroneurons. (3) The archicerebellar cholinergic network appears to be relatively well preserved from undernutrition and, to an even greater extent, from hypothyroidism, compared to other systems of neurotransmission formed later and more widely distributed throughout the cerebellum. The presynaptic compartment seems to be more affected than the postsynaptic compartment. (4) In disagreement with some data in the literature, the abnormalities induced by both abnormal thyroidal and nutritional states were found to be irreversible.

Nicotinic Receptor Abnormalities in the Cerebellar Cortex of Sudden Unexplained Fetal and Infant Death Victims—Possible Correlation With Maternal Smoking

“…The abundance of cholinergic synthetic enzymes during the long cerebellar maturative process (Clos et al., 1989) supports this assertion. More specifically, experimental studies have demonstrated that the dynamic sequence of morphological steps that regularly occur during CC development, mainly consisting in a progressive thinning until the disappearance of the EGL due to cell death or cell migration in the IGL, coincide with the maturation of the cholinergic system (Clos et al., 1989; Court et al., 1995). The activation of the α7-nAChR subtype appears to be particularly involved in the maturation of the granule layers (Caruncho et al., 1997; Opanashuk et al., 2001; Prestori et al., 2013).…”

Regulation of Cholinergic Phenotype in Developing Neurons

“…during embryonic and early postnatal development (Clos et al 1989;Feller et al 1996;Milner and Landmesser 1999;Zoli et al 1995). These cholinergic properties are subsequently down-regulated at later developmental stages that coincide with the glutamatergic synapse formation and increased glutamate-dependent excitatory synaptic activity (Wong 1999).…”

Developmental regulation of nicotinic acetylcholine receptor‐mediated [3H]norepinephrine release from rat cerebellum

“…1991), with particularly high levels of ACh and choline seen in neonatal cerebellum, resulting from a high ratio of ChAT to AChE activities (Kasa et al . 1982; Clos et al . 1989).…”