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Selective immunoles...
Selective immunolesioning of the basal forebrain cholinergic system disrupts short-term memory in rats
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- Leanza, G (författare)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups,University of Catania
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- Muir, J (författare)
- University of Cambridge
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- Nilsson, O G (författare)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Wiley, R G (författare)
- Vanderbilt University
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- Dunnett, S B (författare)
- University of Cambridge
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- Bjorklund, A (författare)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups
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(creator_code:org_t)
- Wiley, 1996
- 1996
- Engelska.
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 8:7, s. 1535-4154
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions displayed a significant delay-dependent decline in performance compared to normal controls, indicating a deficit in short-term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG-saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (>90-95%) depletion of cholinergic neurons throughout the septal-diagonal band area and the nucleus basalis region by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal-diagonal band area and nucleus basalis produce long-lasting impairments in short-term memory, thus providing further support for a role of this system in cognitive functions.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Animals
- Antibodies, Monoclonal/toxicity
- Arecoline/pharmacology
- Cholinergic Agents/toxicity
- Conditioning, Operant/physiology
- Female
- Hippocampus/physiology
- Immunotoxins/toxicity
- Memory Disorders/physiopathology
- Memory, Short-Term/physiology
- N-Glycosyl Hydrolases
- N-Methylscopolamine
- Parasympatholytics/pharmacology
- Prosencephalon/physiology
- Rats
- Rats, Sprague-Dawley
- Reaction Time/drug effects
- Ribosome Inactivating Proteins, Type 1
- Saporins
- Scopolamine/pharmacology
- Scopolamine Derivatives/pharmacology
- Septum Pellucidum/physiology
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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