Mesopontine neurons in schizophrenia

García‐Rill, Edgar; Biedermann, JoAnn; Chambers, Timothy C.; Skinner, R.D.; Mrak, Robert E.; Husain, Muhammad; Karson, Craig N.

doi:10.1016/0306-4522(94)00564-l

Cited by 99 publications

(62 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many of the neurons contained a visible nucleus, but neurons without a visible nucleus also were counted. Cholinergic pedunculopontine nucleus (PPN) neurons were identified by processing sections for NADPH-diaphorase histochemistry as previously described (10). This method selectively labels cholinergic mesopontine neurons.…”

Section: Laboratory Methodsmentioning

confidence: 99%

“…While early work focused on neurochemistry (1), recent post-mortem techniques allow for neuron-counting studies of some of the smaller brain nuclei, such as those found in the brainstem reticular activating system (RAS) (2)(3)(4). The locus coeruleus (LC), the noradrenergic arm of the RAS, comprises approximately 23,000 neurons on each side of the brainstem (5) and provides over 70% of the noradrenergic innervation in the central nervous system (CNS) and probably a higher percent of the ascending noradrenergic innervation (6).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Postmortem Locus Coeruleus Neuron Count in Three American Veterans With Probable or Possible War-Related PTSD

Bracha

García‐Rill²,

Mrak³

et al. 2005

Journal of Neuropsychiatry

View full text Add to dashboard Cite

Objective-Because enhanced CNS noradrenergic postsynaptic responsiveness has been previously shown to contribute to PTSD pathophysiology, we investigated whether war-related posttraumatic stress disorder (WR-PTSD) is associated with a post-mortem change in neuronal counts in the locus coeruleus (LC).Method-Using post-mortem neuromorphometry, we counted the number of neurons in the right LC in seven deceased elderly male veterans. We classified three veterans as cases of probable or possible WR-PTSD.Results-All three veterans with probable or possible WR-PTSD were found to have substantially lower LC neuronal counts compared to four controls (three non-psychiatric veterans and one veteran with alcohol dependence and delirium tremens).Conclusion-To our knowledge, this case series is the first report of LC neuronal counts in patients with PTSD or any other DSM-IV-TR anxiety disorder. Previous post-mortem brain tissue studies of Alzheimer's Disease (AD) demonstrated an upregulation of NE biosynthetic capacity in surviving LC neurons. The finding reported here is consistent with the similar upregulation of NE biosynthetic capacity of surviving LC neurons in veterans who developed WR-PTSD. If replicated, the finding we report here in WR-PTSD may provide further explanation of the demonstrated effectiveness of PTSD treatment with propranolol and prazosin. Larger neuromorphometric studies of the LC in veterans with WR-PTSD and in other stress-induced and fear-circuitry disorders are warranted.

show abstract

Section: Laboratory Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Postmortem Locus Coeruleus Neuron Count in Three American Veterans With Probable or Possible War-Related PTSD

Bracha

García‐Rill²,

Mrak³

et al. 2005

Journal of Neuropsychiatry

View full text Add to dashboard Cite

show abstract

“…A reduced number of cholinergic interneurons was described in the ventral striatum in schizophrenia, 77,78 but the distribution of mesopontine cholinergic neurons has yielded conflicting results. [79][80][81] Analyzing the density of muscarinic receptors, an early study using 3 H-QNB reported a significant reduction in the level of muscarinic receptor binding in the frontal cortex of subjects with schizophrenia compared to healthy controls. 82 This result was not replicated in a later study also using 3 H-QNB, which reported a reduced affinity and increased muscarinic receptor number in orbitofrontal and medial frontal cortex in medicated subjects with schizophrenia, whereas unmedicated subjects with schizophrenia did not differ from controls.…”

Section: Post-mortem Cns Studiesmentioning

confidence: 99%

Towards a muscarinic hypothesis of schizophrenia

Raedler

Bymaster

Tandon³

et al. 2006

Mol Psychiatry

247

211

View full text Add to dashboard Cite

Although the neurotransmitter dopamine plays a prominent role in the pathogenesis and treatment of schizophrenia, the dopamine hypothesis of schizophrenia fails to explain all aspects of this disorder. It is increasingly evident that the pathology of schizophrenia also involves other neurotransmitter systems. Data from many streams of research including preclinical and clinical pharmacology, treatment studies, post-mortem studies and neuroimaging suggest an important role for the muscarinic cholinergic system in the pathophysiology of schizophrenia. This review will focus on evidence that supports the hypothesis that the muscarinic system is involved in the pathogenesis of schizophrenia and that muscarinic receptors may represent promising novel targets for the treatment of this disorder.

show abstract

“…Conversely, muscarinic antagonists used to reduce extrapyramidal side effects associated with APDs (Tandon, 1999) have been reported to exacerbate schizophrenia symptoms and to interfere with the therapeutic effects of APDs (Johnstone et al, 1983;Lo and Tsai, 1996;Kay, 1975, 1979;Tandon et al, 1990). These findings, taken together with postmortem and neuroimaging findings of cholinergic alterations in the brains of schizophrenia patients (eg Crook et al, 2001;Dean et al, 1996;Garcia-Rill et al, 1995;Karson et al, 1991;Raedler et al, 2003;Zavitsanou et al, 2005), have led to a growing interest in the involvement of the cholinergic system in this disorder (eg Hyde and Crook, 2001;Sarter et al, 2005;Tandon et al, 1992;Weiner et al, 2004;Yeomans, 1995). The focus on the cholinergic system has been reinforced by the increasingly acknowledged need for improved treatments of cognitive deficits in schizophrenia (eg Bymaster et al, 2002;Friedman, 2004).…”

Section: Introductionmentioning

confidence: 99%

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Barak

Weiner

2006

Neuropsychopharmacol

View full text Add to dashboard Cite

The fact that muscarinic antagonists may evoke a psychotic state ('antimuscarinic psychosis'), along with findings of cholinergic alterations in schizophrenia, have kindled an interest in the involvement of the cholinergic system in this disorder. Latent inhibition (LI) is a crossspecies phenomenon manifested as a poorer conditioning of a stimulus seen when the stage of conditioning is preceded by a stage of repeated nonreinforced pre-exposure to that stimulus, and is considered to index the capacity to ignore irrelevant stimuli. Amphetamine-induced LI disruption and its reversal by antipsychotic drugs (APDs) is a well-established model of positive symptoms of schizophrenia. Here, we tested whether the muscarinic antagonist scopolamine would disrupt LI and whether such disruption would be reversed by APDs and by the acetylcholinesterase inhibitor physostigmine. The results showed that scopolamine at doses of 0.15 and 0.5 mg/kg disrupted LI, and that this effect was due to the action of the drug in the pre-exposure stage, suggesting a role of muscarinic transmission in attentional processes underlying LI. Both the typical and the atypical APDs, haloperidol and clozapine, reversed scopolamine-induced LI disruption when given in conditioning or in both stages, but not in pre-exposure, indicating that the mechanism of antipsychotic action in this model is independent of the mechanism of action of the propsychotic drug. Scopolamine-induced LI disruption was reversed by physostigmine (0.05 and 0.15 mg/kg), which was ineffective in reversing amphetamine-induced LI disruption, pointing to distinct mechanisms underlying LI disruption by these two propsychotic drugs. The latter was further supported by the finding that unlike amphetamine, the LI-disrupting doses of scopolamine did not affect activity levels. We propose scopolamine-induced LI disruption as a model of cholinergic-related positive symptoms in schizophrenia. Neuropsychopharmacology (2007) 32, 989-999.

show abstract

Mesopontine neurons in schizophrenia

Cited by 99 publications

References 64 publications

Postmortem Locus Coeruleus Neuron Count in Three American Veterans With Probable or Possible War-Related PTSD

Postmortem Locus Coeruleus Neuron Count in Three American Veterans With Probable or Possible War-Related PTSD

Towards a muscarinic hypothesis of schizophrenia

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Contact Info

Product

Resources

About