Choline High‐Affinity Uptake and Metabolism and Choline Acetyltransferase Activity in the Striatum of Rats Chronically Treated with Neuroleptics

Pedata, Felicita; Sorbi, Sandro; Pepeu, Giancarlo

doi:10.1111/j.1471-4159.1980.tb03698.x

Cited by 23 publications

(9 citation statements)

References 19 publications

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“…Recent studies have reported that the density of cholinergic neurons in the limbic striatum is decreased in patients with schizophrenia (Holt et al, 1999) and that the lowest density of ChAT+ neurons was found in two schizophrenic individuals that had not been treated with neuroleptics. This is in agreement with pharmacological data suggesting that dopamine D2 receptor antagonists increase cholinergic neuron activity, choline utilization and acetylcholine levels in the striatum (Pedata et al, 1980; Rupniak et al, 1986). In aggregate, the above findings are not consistent with the idea that the decrease in ChAT+ cells observed in the present study is attributable to neuroleptic treatment.…”

Section: Discussionsupporting

confidence: 92%

Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome

Kataoka

Kalanithi

Grantz

et al. 2009

J of Comparative Neurology

424

343

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Cortico-basal ganglia neuronal ensembles bring automatic motor skills into voluntary control and integrate them into ongoing motor behavior. A 5% decrease in caudate (Cd) nucleus volume is the most consistent structural finding in the brain of patients with Tourette syndrome (TS), but the cellular abnormalities that underlie this decrease in volume are unclear. In this paper, the density of different types of interneurons and medium spiny neurons (MSNs) in the striatum was assessed in the postmortem brains of 5 TS subjects as compared with normal controls (NC) by unbiased stereological analyses. TS patients demonstrated a 50-60% decrease of both parvalbumin (PV)+ and choline acetyltransferase (ChAT)+ cholinergic interneurons in the Cd and the putamen (Pt). Cholinergic interneurons were decreased in TS patients in the associative and sensorimotor regions but not in the limbic regions of the striatum, such that the normal gradient in density of cholinergic cells (highest in associative regions, intermediate in sensorimotor and lowest in limbic regions) was abolished. No significant difference was present in the densities of medium-sized calretinin (CR)+ interneurons, MSNs and total neurons. The selective deficit of PV+ and cholinergic striatal interneurons in TS subjects may result in an impaired cortico/thalamic control of striatal neuron firing in TS.

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Section: Discussionsupporting

confidence: 92%

Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome

Kataoka

Kalanithi

Grantz

et al. 2009

J of Comparative Neurology

424

343

View full text Add to dashboard Cite

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“…Observational analysis of search behaviors (head turns and slowing in the platform area) was more apparent in the RISP group (and diminished in the HAL group), however. The immunohistochemical studies confirmed several earlier observations that HAL treatment negatively alters central cholinergic systems (Pedata et al, 1980;Mahadik et al, 1988;Korenovsky et al, 1990;Miller and Chouinard, 1993;Angelucci et al, 2000). These effects support the cognitive deficits observed after HAL exposure.…”

Section: Discussionsupporting

confidence: 87%

Differential Effects of Haloperidol, Risperidone, and Clozapine Exposure on Cholinergic Markers and Spatial Learning Performance in Rats

Terry

Hill

Parikh

et al. 2002

Neuropsychopharmacol

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Haloperidol (HAL), a potent typical antipsychotic, continues to be a frequently prescribed medication for behavioral disturbances associated particularly with schizophrenia despite well-documented adverse effects associated with its chronic use. Animal experiments have even indicated that HAL can damage cholinergic pathways and thus could be especially deleterious to those experiencing cognitive deficits. However, several recent clinical studies indicate that atypical antipsychotics may actually improve cognitive function in some patients, although this assertion requires further investigation. The purpose of this study was to compare the effects of prior chronic (45-or 90-day) oral exposure to HAL and the atypical antipsychotics risperidone (RISP) and clozapine (CLOZ) on cognitive performance and central cholinergic markers in rats. All analyses were done after 4 days of drug washout in order to minimize direct drug effects. Learning performance and choline acetyltransferase (ChAT) levels were assessed in a water maze task and with immunofluorescence staining, respectively. HAL significantly impaired learning performance after 90 but not after 45 days of treatment when compared to both vehicle controls and the atypical agents, while RISP slightly improved task performance. Both 45 and 90 days of previous HAL exposure reduced ChAT staining in several brain regions, including the cortex, caudate-putamen, and hippocampus. ChAT staining in the caudate-putamen and hippocampus was also decreased after 90 days of RISP exposure, raising the possibility of deleterious cognitive effects after exposure to this dosage for longer periods of time. The results suggest that antipsychotic drugs exert differential and temporally dependent effects on central cholinergic neurons and learning performance.

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“…Recent studies have reported that the density of cholinergic neurons in the limbic striatum is decreased in patients with schizophrenia (Holt et al,1999) and that the lowest density of ChAT+ neurons was found in two schizophrenic individuals that had not been treated with neuroleptics. This is in agreement with pharmacological data suggesting that dopamine D2 receptor antagonists increase cholinergic neuron activity, choline utilization, and acetylcholine levels in the striatum (Pedata et al,1980; Rupniak et al,1986). In aggregate, the above findings are not consistent with the idea that the decrease in ChAT+ cells observed in the present study is attributable to neuroleptic treatment.…”

Section: Discussionsupporting

confidence: 91%

P48 is a predictive marker for outcome of postoperative interferon‐α treatment in patients with hepatitis B virus infection‐related hepatocellular carcinoma

Qian

Zhang

et al. 2006

Cancer

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BACKGROUND.Postoperative interferon‐α (IFN‐α) therapy improved survival in patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC). The identification of predictive markers of outcome will help to select patients who are most likely to benefit from treatment.METHODS.An immunohistochemical study of P48 was performed on specimens that were collected from patients in a randomized trial who received postoperative IFN‐α therapy (Group 1; n = 80 patients) and who did not receive postoperative IFN‐α therapy (Group 2; n = 75 patients). Positive P48 expression was graded as ≥20% positive cells in 1 sample.RESULTS.Eighty‐one patients were positive for P48, and 74 patients were negative for P48. The clinicopathologic data were comparable between patients with P48‐negative and P48‐positive staining. Disease‐free survival (DFS) and overall survival (OS) in P48‐positive patients were better than that in P48‐negative patients in Group 1 (DFS, P = .036; OS, P = .014), however, DFS and OS did not differ between patients with positive and negative P48 in Group 2. OS in P48‐positive patients from Group 1 was better than that in patients with P48‐positive patients from Group 2 (OS, P = .001) but did not differ when P48 was negative. In Group 1, the risk factors for DFS were cirrhosis and P48 staining, and the risk factors for OS were tumor differentiation and P48 staining. Receiver operating curve analysis indicated that, in the first 2 years of DFS, combined cirrhosis and P48 had good predictive accuracy; and, in the first 4 years of OS, combined tumor differentiation and P48 had good predictive accuracy.CONCLUSIONS.P48 was useful as a predictive marker of outcome after postoperative IFN‐α treatment in patients with HBV‐related HCC. Cancer 2006. © 2006 American Cancer Society.

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Choline High‐Affinity Uptake and Metabolism and Choline Acetyltransferase Activity in the Striatum of Rats Chronically Treated with Neuroleptics

Cited by 23 publications

References 19 publications

Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome

Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome

Differential Effects of Haloperidol, Risperidone, and Clozapine Exposure on Cholinergic Markers and Spatial Learning Performance in Rats

P48 is a predictive marker for outcome of postoperative interferon‐α treatment in patients with hepatitis B virus infection‐related hepatocellular carcinoma

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