Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia

Marutle, Amelia; Zhang, Xiao; Court, Jennifer A.; Piggott, Margaret A.; Johnson, Mark; Perry, Robert H.; Perry, Elaine K.; Nordberg, Agneta

doi:10.1016/s0891-0618(01)00117-x

Cited by 164 publications

(123 citation statements)

References 53 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…These are but two examples of sex-specific effects of prenatal exposure to nicotine that may translate into long-lasting morphological changes in serotonin-rich regions. One such region is the OFC (Tork, 1990;Dillon et al, 1991;Marutle et al, 2001;Tauscher et al, 2001) and this is where we found significant effects of PEMCS on cortical thickness in the female adolescents. In general, thickness of a cortical region, as estimated from MRI, most likely reflects the volume of various cellular compartments constituting the cortex (axons (29%), dendrites (30%), cell bodies and vessels (14%), and glia (10%) percentages based on the mouse cerebral cortex) and the effect of the adjacent white matter (Braitenberg, 2001; Figure 1 Surface maps of statistical significance of PEMCS on cortical thickness.…”

Section: Discussionmentioning

confidence: 81%

Prenatal Exposure to Maternal Cigarette Smoking and the Adolescent Cerebral Cortex

Toro

Leonard

Lerner

et al. 2007

Neuropsychopharmacol

130

View full text Add to dashboard Cite

Smoking during pregnancy is associated with long-term consequences on offspring behavior. We measured thickness of the cerebral cortex using magnetic resonance images obtained in 155 adolescents exposed in utero to maternal smoking and compared them with 159 non-exposed subjects matched by maternal education. Orbitofrontal, middle frontal, and parahippocampal cortices were thinner in exposed, as compared with non-exposed, individuals; these differences were more pronounced in female adolescents. In exposed females, the thickness of the orbitofrontal cortex correlated negatively with a self-rated assessment of caring, one of the components of a model of positive youth development. These findings provide evidence of the long-term impact of prenatal environment on a neural substrate of cognition and social behavior.

show abstract

Section: Discussionmentioning

confidence: 81%

Prenatal Exposure to Maternal Cigarette Smoking and the Adolescent Cerebral Cortex

Toro

Leonard

Lerner

et al. 2007

Neuropsychopharmacol

130

View full text Add to dashboard Cite

show abstract

“…This P50 auditory evoked potential deficit is linked to 15q14 at a polymorphic marker < 120 kb from the α7 gene [39]. Postmortem studies which demonstrate decreased α7 nicotinic cholinergic receptor binding have been noted in the reticular nucleus of the thalamus, the hippocampus, the cingulate cortex and the frontal lobe regions [49,50,51,52]. Nicotine has brief cognitive-enhancing effects in schizophrenia (74,75,76,77,78,79,80].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the deficits in P50 evoked potentials and the functional promoter polymorphisms in the CHRNA7 region, people with schizophrenia also have abnormalities in expression and regulation of central nicotinic cholinergic receptors. Decreased α7 nicotinic cholinergic receptor binding has been noted in the reticular nucleus of the thalamus, the hippocampus, the cingulate cortex and the frontal lobe regions [49,50,51,52].…”

mentioning

confidence: 99%

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

Olincy

Stevens

2007

Biochemical Pharmacology

125

View full text Add to dashboard Cite

Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinic in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal α7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for α7 subtype of the nicotinic cholinergic receptors in these processes. Rodent studies also demonstrated the efficacy of a selective partial α7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for α7 nicotinic activity may have utility in treating certain symptoms of schizophrenia. KeywordsSchizophrenia; nicotinic receptors; DMXBA; P50 auditory evoked potential; cognitive deficits; nicotine Although the positive symptoms such as hallucinations and delusions of schizophrenia are partially treated with the available antipsychotic medications, social and occupational dysfunction remains a major issue in treating this disorder. Cognitive deficits have been identified as more closely related to ability to adequately function [1]. In the search for new and more effective therapeutic agents for schizophrenia, recent attention has turned the nicotinic cholinergic receptors system. α7 and P50 Auditory GatingPeople with schizophrenia, in addition to the cardinal symptoms of hallucinations and delusions, suffer from the inability to focus attention. This may stem from being overwhelmed

show abstract

“…In rodents, a4b2 subunit of nAChRs, but not a7, appears to regulate acoustic PPI (Schreiber et al, 2002). However, there is strong evidence suggesting that a7 nAChR (for a recent review see Martin and Freedman, 2007) and to a lesser extent a4b2 nAChR (Breese et al, 2000;Durany et al, 2000;Marutle et al, 2001;Faraone et al, 2004;De Luca et al, 2006) are involved in the pathology of schizophrenia. Subtype-specific nAChRs compounds are now becoming available for human studies.…”

Section: Discussionmentioning

confidence: 99%

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

Hong

Wonodi

Lewis

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p ¼ 0.008) with no drug by diagnosis interaction (p ¼ 0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r ¼ 0.59, p ¼ 0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p ¼ 0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.

show abstract

Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia

Cited by 164 publications

References 53 publications

Prenatal Exposure to Maternal Cigarette Smoking and the Adolescent Cerebral Cortex

Prenatal Exposure to Maternal Cigarette Smoking and the Adolescent Cerebral Cortex

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

Contact Info

Product

Resources

About