Nicotinic receptors autism

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). 

Lee M, Martin-Ruiz C, Graham A, Court J, Jaros E, Petty R, Iversen P, Baumtm M, Perry E 2002) Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain 125 1483-1495 Lerer E, Levi S, Salomon S, Darvasi A, Yitmiya N, Ebstein RP (2008) Association between the oxytocin receptor (OXTR) gene and autism relationship to Vineland adaptive behavior scales and cognition. Mol Psychiatry 13 980-988... 

Martin-Ruiz CM, Lee M, Perry RH, Baumann M, Court JA, Perry EK (2004) Molecular analysis of nicotinic receptor expression in autism. Brain Res Mol Brain Res 123 81-90 Martineau J, Herault J, Petit E, Guerin P, Hameury L, Perrot A, MaUet J, Sauvage D, Lelord G, Muh JP (1994) Catecholaminergic metabolism and autism. Dev Med Child Neurol 36 688-697... 

Bednar I, Paterson D, Marutle A, Pham TM, Svedberg M, HeUstrom-Lindahl E, Mousavi M, Court J, Morris C, Perry E, Mohammed A, Zhang X, Nordberg A (2002) Selective nicotinic receptor consequences in APP(SWE) transgenic mice. Mol Cell Neurosci 20 354-365 Bejerot S, Nylander L (2003) Low prevalence of smoking in patients with autism spectrum disorders. Psychiatry Res 119 177-182... 

Martin-Ruiz CM, Lee M, Perry RH, Baumann M, Court JA, Perry EK (2004) Molecular analysis of nicotinic receptor expression in autism. Brain Res Mol Brain Res 123 81-90... 

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... 

In the thalamus, nicotinic receptor subunits were decreased in the numbers of a and P2 immunoreactive neurons in the paraventricular nucleus (PV) and nucleus reuniens (NR) in autistic subjects (Ray et al., 2005 Fig. 4). These deficits in nicotinic receptor subunits perhaps result in the failure of the PV and NR (and so the thalamus) to correctly modulate sensory input. This effect would then be transferred throughout the limbic system to other parts of the brain, contributing to the incorrect sensory processing found in autism (Martin-Ruiz et al., 2004). The co-expression of a and glutamic acid decarboxylase (GAD) study indicated that despite the decrease in a7, the expression of GAD in the PV was similar in both autistic and control subjects (Ray et al., 2005). This suggests that the decrease in a7 subunits in the thalamus is not associated with the GABAergic system. 

Lee M, Martin-Ruiz CM, Graham AJ, Court JA, Jaros E, Perry RH, Iverson P, Bauman ML, Perry EK (2002) Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain 125 1483-1495. 

Keywords Receptors, nicotinic Parkinson s disease Alzheimer s disease Schizophrenia Autism Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) CHRNA5 CHRNA3 Nicotine dependence Tourette s syndrome Down syndrome... 

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