Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats
Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2016-10-01
|
| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/9/10/1159 |
| _version_ | 1818250113615659008 |
|---|---|
| author | Uta Waterhouse Vic E. Roper Katharine A. Brennan Bart A. Ellenbroek |
| author_facet | Uta Waterhouse Vic E. Roper Katharine A. Brennan Bart A. Ellenbroek |
| author_sort | Uta Waterhouse |
| collection | DOAJ |
| description | Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD) 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI), latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI) and selective (LI) improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI) and induced a global enhancement of sensorimotor gating (PPI). |
| first_indexed | 2024-12-12T15:47:14Z |
| format | Article |
| id | doaj.art-3bbc8ca8d28444e0ae352acc1b3bfd57 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-12T15:47:14Z |
| publishDate | 2016-10-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-3bbc8ca8d28444e0ae352acc1b3bfd572022-12-22T00:19:42ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112016-10-019101159116710.1242/dmm.025072025072Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in ratsUta Waterhouse0Vic E. Roper1Katharine A. Brennan2Bart A. Ellenbroek3 School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington 6140, New Zealand School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington 6140, New Zealand School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington 6140, New Zealand School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington 6140, New Zealand Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD) 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI), latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI) and selective (LI) improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI) and induced a global enhancement of sensorimotor gating (PPI).http://dmm.biologists.org/content/9/10/1159Prenatal immune challengeLipopolysaccharideMemory |
| spellingShingle | Uta Waterhouse Vic E. Roper Katharine A. Brennan Bart A. Ellenbroek Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats Disease Models & Mechanisms Prenatal immune challenge Lipopolysaccharide Memory |
| title | Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats |
| title_full | Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats |
| title_fullStr | Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats |
| title_full_unstemmed | Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats |
| title_short | Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats |
| title_sort | nicotine ameliorates schizophrenia like cognitive deficits induced by maternal lps exposure a study in rats |
| topic | Prenatal immune challenge Lipopolysaccharide Memory |
| url | http://dmm.biologists.org/content/9/10/1159 |
| work_keys_str_mv | AT utawaterhouse nicotineamelioratesschizophrenialikecognitivedeficitsinducedbymaternallpsexposureastudyinrats AT viceroper nicotineamelioratesschizophrenialikecognitivedeficitsinducedbymaternallpsexposureastudyinrats AT katharineabrennan nicotineamelioratesschizophrenialikecognitivedeficitsinducedbymaternallpsexposureastudyinrats AT bartaellenbroek nicotineamelioratesschizophrenialikecognitivedeficitsinducedbymaternallpsexposureastudyinrats |