Cholinergic system impairment

Basu, N., Scheuhammer, A.M., and Rouvinen-Watt, K. et al. (2006). Methyl mercury impairs components of the cholinergic system in captive mink. Toxicology Science 91,... 

Basu N, Scheuhammer AM, Rouvinen-Watt K, Grochowina N, Klenavic K, Evans RD, Chan HM. 2006. Methyhnercury impairs components of the cholinergic system in captive mink (Mustela vison). Toxicol Sci 91 202-209. 

Lesions of the basal forebrain cholinergic system using a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) result in impaired attentional, but not mnemonic, function in rats (Muir et al., 1995) and monkeys (Voytko et al., 1994), an effect which has been confirmed using more selective IgG-saporin lesions (Baxter et al., 1995 Everitt 8c Robbins, 1997). 

Generalized muscular weakness associated with signs of systemic cholinergic autonomic impairment has been reported. 

Other approaches that are not related to the cholinergic system that are used to treat learning, memory, and cognitive impairment irrespective of disease type are with so-called nootropics (Schindler et al., 1984). These are compounds without either sedative or stimulatory properties that may positively affect blood flow and metabolism in the brain. They tend to share the ability to protect (rats) against chemically induced disruptions of memory deficits and learned avoidance behavior. Among the promising compounds are several 2-(N-acetamido)-pyrrolidones. 

The cholinergic system in insects is the main target of insecticides. One class of molecules, the neonicotinoids, induces direct activation of the neuronal nicotinic acetylcholine receptors (nAChRs). In the honey bee these receptors are mainly distributed in the olfactory pathways that link sensory neurons to antennal lobes and mushroom bodies. These structures seem to play an important role in olfactory conditioning. We have previously shown that cholinergic antagonists injected in different parts of the brain impaired the formation and retrieval of olfactory memory. We then advanced the hypothesis that, through the activation of the nAChR, the neonicotinoid imidacloprid (IMI) would lead to facilitation of the memory trace. 

This, in turn, has led to investigation of OP-mediated suppression of the hypothalamic-pituitary-adrenal axis (Pena-Philippides et al., 2007). However, anti-ChEs were also found to initiate acute immune responses. For example, the nerve agent soman induces an increase in the pro-inflammatory cytokine TNFa, IL-lp, and fL-6 in rats, including in the brain, where IL-lp is thought to contribute to irreversible brain damage (Banks and Lein, 2012). This bidirectional impairment of immune functions may reflect systemic responses that affect more than the cholinergic system alone. 

---