Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice
<p>Abstract</p> <p>Background</p> <p>Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hy...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-11-01
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| Series: | Behavioral and Brain Functions |
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| Online Access: | http://www.behavioralandbrainfunctions.com/content/8/1/54 |
| _version_ | 1818676724915765248 |
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| author | Adriani Walter Koot Susanne Columba-Cabezas Sandra Romano Emilia Travaglini Domenica van den Bos Ruud Granstrem Oleg Ali Syed F Laviola Giovanni |
| author_facet | Adriani Walter Koot Susanne Columba-Cabezas Sandra Romano Emilia Travaglini Domenica van den Bos Ruud Granstrem Oleg Ali Syed F Laviola Giovanni |
| author_sort | Adriani Walter |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype.</p> <p>Methods</p> <p>Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec).</p> <p>Results</p> <p>DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies.</p> <p>Conclusions</p> <p>Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders.</p> |
| first_indexed | 2024-12-17T08:48:02Z |
| format | Article |
| id | doaj.art-6f85225b36f74f2bbe5e2e3732403f73 |
| institution | Directory Open Access Journal |
| issn | 1744-9081 |
| language | English |
| last_indexed | 2024-12-17T08:48:02Z |
| publishDate | 2012-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Behavioral and Brain Functions |
| spelling | doaj.art-6f85225b36f74f2bbe5e2e3732403f732022-12-21T21:56:10ZengBMCBehavioral and Brain Functions1744-90812012-11-01815410.1186/1744-9081-8-54Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in miceAdriani WalterKoot SusanneColumba-Cabezas SandraRomano EmiliaTravaglini Domenicavan den Bos RuudGranstrem OlegAli Syed FLaviola Giovanni<p>Abstract</p> <p>Background</p> <p>Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype.</p> <p>Methods</p> <p>Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec).</p> <p>Results</p> <p>DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies.</p> <p>Conclusions</p> <p>Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders.</p>http://www.behavioralandbrainfunctions.com/content/8/1/54Auto-antibodies to neuro-receptorsDATDelay of rewardFlexibility of choice behaviourADHDOCD |
| spellingShingle | Adriani Walter Koot Susanne Columba-Cabezas Sandra Romano Emilia Travaglini Domenica van den Bos Ruud Granstrem Oleg Ali Syed F Laviola Giovanni Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice Behavioral and Brain Functions Auto-antibodies to neuro-receptors DAT Delay of reward Flexibility of choice behaviour ADHD OCD |
| title | Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice |
| title_full | Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice |
| title_fullStr | Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice |
| title_full_unstemmed | Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice |
| title_short | Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice |
| title_sort | immunization with dat fragments is associated with long term striatal impairment hyperactivity and reduced cognitive flexibility in mice |
| topic | Auto-antibodies to neuro-receptors DAT Delay of reward Flexibility of choice behaviour ADHD OCD |
| url | http://www.behavioralandbrainfunctions.com/content/8/1/54 |
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