Distribution of nicotinic acetylcholine receptor subunits α7 and β2 in the human brainstem and hippocampal formation

Machaalani, Rita; Kashi, Petra K.; Waters, Karen A.

doi:10.1016/j.jchemneu.2010.05.009

Cited by 32 publications

(17 citation statements)

References 60 publications

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“…In this study, α4 and β2 subunit expression was highest in the CA3 region suggesting that those nAChRs may be associated with connecting the CA3 to the CA1 region via the Schaffer Collateral Axons. The finding that β2 expression was highest in the CA3 region is consistent with the human infant (Machaalani et al, 2010) while the distribution of α4 in CA3 was consistent with findings in the postnatal rat (Huang et al, 2007; Huang and Winzer‐Sehan, 2006) and adult primate (Han et al, 2000). Interestingly, we did not find α5 in the hippocampus even at high antibody concentration, consistent with Han et al (2000), who found no α5 mRNA expression in the CA pyramidal layer nor the DG of adult monkeys (Han et al, 2000).…”

Section: Discussionsupporting

confidence: 84%

Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem

Vivekanandarajah

Waters

Machaalani

2015

Intl J of Devlp Neuroscience

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Postnatal exposure to cigarette smoke during infancy is associated with increased number of respiratory illnesses, impaired pulmonary function, and the occurrence of Sudden Infant Death Syndrome (SIDS). It is also associated with reduced cognitive functioning and attention deficits in childhood. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR). Using a piglet model of postnatal nicotine exposure, we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 in the brainstem medulla and the hippocampus, given the role of these structures in cardiorespiratory control and cognition, respectively. We compared piglets exposed postnatally to 2mg/kg/day nicotine for 14 days (n=14: 7 males: 7 females) to controls (n=14: 7 males: 7 females). In the hippocampus, decreased expression was seen for α3 in CA1 (p=0.017), α9 in CA1 (p<0.001) and CA2 (p<0.001), β1 in CA1 (p=0.001) and CA2 (p=0.001) and β2 in CA3 (p=0.036). In the medulla, the nucleus of the spinal trigeminal tract had increased α2 and α4; vestibular nucleus increased α2 and α3, and decreased α4; hypoglossal decreased α3 and β1; dorsal motor nucleus of the vagus decreased α4 and β1. This is the first demonstration that non-classical nAChR subunits are affected by postnatal nicotine in the developing brain, and the implications are discussed.

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Section: Discussionsupporting

confidence: 84%

Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem

Vivekanandarajah

Waters

Machaalani

2015

Intl J of Devlp Neuroscience

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“…13, 14, 20, 57 nAChRs operate through a cycle of activation, desensitization and reactivation 58 that, in the case of brainstem synaptic transmission with diffuse inputs impinging on HMs, include early facilitation of glutamate release followed by depression, whereas synaptic inhibition is enhanced 13, 20 (Figure 8b). Direct activation of nAChRs on motoneurons reduces ROS production, enhances Hsp70 expression and uncouples Cx36-mediated intercellular communication.…”

Section: Discussionmentioning

confidence: 99%

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

et al. 2017

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Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca2+ transients time locked among nearby HMs, whose number fell by about 30% 4 h later. As nicotine or the gap junction blocker carbenoxolone suppressed bursting, we studied connexin 36 (Cx36), which constitutes gap junctions in neurons and found it largely expressed by HMs. Cx36 was downregulated when nicotine or carbenoxolone was co-applied with TBOA. Expression of Cx36 was preferentially observed in cytosolic rather than membrane fractions after nicotine and TBOA, suggesting protein redistribution with no change in synthesis. Nicotine raised the expression of heat shock protein 70 (Hsp70), a protective factor that binds the apoptotic-inducing factor (AIF) whose nuclear translocation is a cause of cell death. TBOA increased intracellular AIF, an effect blocked by nicotine. These results indicate that activation of neuronal nicotinic receptors is an early tool for protecting motoneurons from excitotoxicity and that this process is carried out via the combined decrease in Cx36 activity, overexpression of Hsp70 and fall in AIF translocation. Thus, retarding or inhibiting HM death may be experimentally achieved by targeting one of these processes leading to motoneuron death.

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“…The results indicated that b4 nAChR subunits can coassemble with a7 nAChR subunits but that the pharmacological properties of the resulting receptors showed no significant differences in the response time course or pharmacological profile from homomeric a7 nAChRs, except for a minor difference in the sensitivity to cytisine (Criado et al, 2012). Additional studies examined the localization of a7 with b2 nAChR subunits in brain stem and hippocampus and suggested that coassembly of these subunits have a developmental role and influence the occurrence of sudden infant death syndrome (Machaalani et al, 2011;Machaalani et al, 2010). A word of caution should, however, be given, because these studies were conducted with antibodies and it is known that such labeling might be inaccurate (Moser et al, 2007;Jones and Wonnacott, 2005).…”

Section: The A7 Nicotinic Acetylcholine Receptor Heteromersmentioning

confidence: 97%

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

et al. 2015

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Distribution of nicotinic acetylcholine receptor subunits α7 and β2 in the human brainstem and hippocampal formation

Cited by 32 publications

References 60 publications

Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem

Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

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