| Title |
N-acetyl cysteine reverses bio-behavioural changes induced by prenatal inflammation, adolescent methamphetamine exposure and combined challenges
|
|---|---|
| Published in |
Psychopharmacology, November 2017
|
| DOI | 10.1007/s00213-017-4776-5 |
| Pubmed ID | |
| Authors |
Twanette Swanepoel, Marisa Möller, Brian Herbert Harvey |
| Abstract |
Schizophrenia is associated with prenatal inflammation and/or postnatal stressors such as drug abuse, resulting in immune-redox dysfunction. Antioxidants may offer therapeutic benefits. The objective of this study is to investigate N-acetyl cysteine (NAC) as a therapeutic antioxidant to reverse schizophrenia-like bio-behavioural changes in rats exposed to maternal immune activation (MIA), adolescent methamphetamine (MA) or a combination thereof. Sprague-Dawley offspring prenatally exposed to saline/lipopolysaccharide (LPS) received saline or MA (0.2-6 mg kg(-1) twice daily × 16 days) during adolescence and divided into LPS, MA and LPS + MA groups. Vehicle/NAC (150 mg kg(-1) × 14 days) was administered following MA/saline exposure on postnatal day 51-64. Social interaction, novel object recognition and prepulse inhibition (PPI) of startle, as well as regional brain monoamines, lipid peroxidation, plasma reactive oxygen species (ROS) and pro- and anti-inflammatory cytokines (TNF-α; IL-10), were assessed. NAC reversed LPS, MA and LPS + MA-induced anxiety-like social withdrawal behaviours, as well as MA and LPS + MA-induced deficits in recognition memory. PPI deficits were evident in MA, LPS and LPS + MA models, with NAC reversing that following LPS + MA. NAC reversed LPS, MA and LPS + MA-induced frontal cortical dopamine (DA) and noradrenaline (NA) elevations, LPS and LPS + MA-induced frontal cortical 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and striatal NA deficits as well as LPS + MA-induced frontal cortical 5-HT turnover. Decreased IL-10 in the LPS, MA and LPS + MA animals, and increased TNF-α in the LPS and MA animals, was reversed with NAC. NAC also reversed elevated lipid peroxidation and ROS in the LPS and LPS + MA animals. Prenatal LPS, LPS + postnatal MA challenge during adolescence, and to a lesser extent MA alone, promotes schizophrenia-like bio-behavioural changes later in life that are reversed by NAC, emphasizing therapeutic potential for schizophrenia and MA-associated psychosis. The nature and timing of the dual-hit are critical. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 126 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 126 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 20 | 16% |
| Student > Ph. D. Student | 18 | 14% |
| Researcher | 14 | 11% |
| Student > Bachelor | 12 | 10% |
| Student > Doctoral Student | 9 | 7% |
| Other | 20 | 16% |
| Unknown | 33 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Psychology | 21 | 17% |
| Neuroscience | 15 | 12% |
| Medicine and Dentistry | 10 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 6% |
| Social Sciences | 7 | 6% |
| Other | 22 | 17% |
| Unknown | 43 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 November 2022.
All research outputs
#14,181,328
of 23,179,757 outputs
Outputs from Psychopharmacology
#4,051
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Outputs of similar age
#177,732
of 331,796 outputs
Outputs of similar age from Psychopharmacology
#27
of 45 outputs
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