Cholinergic systems abnormalities

Recent research has indicated select abnormalities in the cholinergic system (Perry et al., 2001). Although previously unexamined neurochemically, there was an indication that the cholinergic system may be involved in autism, with abnormalities reported in neurons in the basal forebrain (Bauman Kemper, 1994). Perry et al. (2001) found extensive loss of high affinity nicotinic receptors from the neocortex (frontal and parietal), and from the cerebellum (Lee, et al., in preparation). Nicotinic receptors are implicated in attention, and also consciousness as many general anaesthetics block the receptor channel (Chapter 9). 

Depression. Depression results from decreased efficacy of aminergic neuromodulation and reciprocal enhancement of the cholinergic system. Thus the set-point level of M declines. When subjects go to sleep they spend less time in stage IV and pass more rapidly to REM (seen as a decreased REM latency) and they spend a longer time in a more intense first REM period. When antidepressant medication raises M back up to normal levels, these sleep abnormalities disappear. 

Q3 Post-mortem examinations of the brains of patients with Alzheimer s disease show loss of cortical neurones and abnormal depositions of proteins in the cerebral tissues. The normal structure of the brain is modified by /l-amyloid plaques, sometimes called senile plaques, and neurofibrillary tangles produced by abnormal neurones. Neurochemical changes in the brain occur, mainly involving cholinergic systems but also other neurotransmitters and neuro modulators. 

It was suggested that cognitive dysfunction in PD, similarly to AD results from loss of cholinergic neurons in the nucleus basalis Meynert (Whitehouse, 1981). However, it was reported by Perry et al. (1985) that dementia in this disease usually occurs in the absence of substantial Alzheimer type changes in the cortex and may be related to abnormalities in the cortical cholinergic system. 

The cholinergic system in autism has been investigated in a number of post-mortem studies (Table 1). In the parietal and frontal cortices of autistic adult subjects, levels of nicotinic receptors were 65-73% lower than in controls (Perry et al., 2001). In the parietal cortex specifically, there were lower levels of a4 and f)2 nicotinic receptor subunits, the high-affinity-type nicotinic receptor (Fig. 4). These abnormalities... 

David E. Kuhl of the University of Michigan, who developed the first clinical tomography machine in 1963, has focused much of his research on the cholinergic system in Alzheimer s disease. In patients with early Alzheimer s, the postero-lateral part of the brain has decreased glucose metabolism, in regions of abnormal ACh synthesis. 

Diazinon produces visible Type I and II ter-atisms when injected into chicken embryos. Type I teratisms (related to tissue NAD depression) included abnormal beaks, abnormal feathering, and shortened limbs. Type II teratisms, which included short and wryneck, leg musculature hypoplasia, and rump-lessness were associated with dismptions in the nicotinic cholinergic system. The severity of effects depended on embryo age and was dose related. Chick embryos (age 48 h) receiving 25.0 xg or more of diazinon/embryo had cervical notochord and neural tube malformations at 96 h, and short neck at 19 days. Wryneck occurred at doses ranging from... 

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