PMID- 29415038
OWN - NLM
STAT- MEDLINE
DCOM- 20180412
LR  - 20200306
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 2
DP  - 2018
TI  - BACHD rats expressing full-length mutant huntingtin exhibit differences in social 
      behavior compared to wild-type littermates.
PG  - e0192289
LID - 10.1371/journal.pone.0192289 [doi]
LID - e0192289
AB  - BACKGROUND: Huntington disease (HD) is a devastating inherited neurodegenerative 
      disorder characterized by progressive motor, cognitive, and psychiatric symptoms 
      without any cure to slow down or stop the progress of the disease. The BACHD rat 
      model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 
      97 polyQ repeats has been recently established as a promising model which 
      reproduces several HD-like features. While motor and cognitive functions have 
      been characterized in BACHD rats, little is known about their social phenotype. 
      OBJECTIVE: This study focuses especially on social behavior since evidence for 
      social disturbances exists in human patients. Our objective was to compare social 
      behavior in BACHD and wild-type (WT) rats at different ages, using two different 
      measures of sociability. METHODS: Animals were tested longitudinally at the age 
      of 2, 4 and 8 months in the social interaction test to examine different 
      parameters of sociability. A separate cohort of 7 month old rats was tested in 
      the three chamber social test to measure both sociability and social novelty. 
      Gene expression analyses in 8 months old animals were performed by real time 
      qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors 
      and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed 
      behavioral alterations. RESULTS: In the social interaction test, BACHD rats 
      showed age-dependent changes in behaviour when they were-re introduced to their 
      cagemate after a 24 hours-period of individual housing. The time spent on nape 
      attacks increased with aging. Furthermore, a significant higher level of pinning 
      at 2 months of age was shown in the BACHD rats compared to wild-types, followed 
      by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a 
      decreased active social behaviour compared to wild-types, reflected by 
      genotype-effects on approaching, following and social nose contact. In the three 
      chamber social test, BACHD rats seemed to show a mild deficit in preference for 
      social novelty, but no changes in social interest. Molecular analyses revealed 
      that BACHD animals exposed to the social interaction test displayed decreased 
      mRNA levels of the total form of BDNF in ventral striatum and unaltered striatal 
      expression of D1 and D2 dopamine receptors. CONCLUSIONS: Taken together, these 
      results indicate deficits in several parameters representative of sociability. 
      Altered BDNF expression in the ventral striatum may contribute to the deficits in 
      sociability in 8 months old BACHD rats. These data support the validity of the 
      BACHD rat model in mimicking features of certain social deficits that could be 
      relevant to symptoms in patients.
FAU - Manfre, Giuseppe
AU  - Manfre G
AD  - Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive 
      Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
AD  - Noldus Information Technology BV, Wageningen, The Netherlands.
AD  - Institute of Medical Genetics and Applied Genomics, University of Tubingen, 
      Tubingen, Germany.
FAU - Novati, Arianna
AU  - Novati A
AD  - Institute of Medical Genetics and Applied Genomics, University of Tubingen, 
      Tubingen, Germany.
AD  - Centre of Rare Diseases, University of Tubingen, Tubingen, Germany.
FAU - Faccini, Ilaria
AU  - Faccini I
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan, 
      Milan, Italy.
FAU - Rossetti, Andrea C
AU  - Rossetti AC
AD  - Department of Medical Biotechnology and Translational Medicine, University of 
      Milan, Milan, Italy.
FAU - Bosch, Kari
AU  - Bosch K
AD  - Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive 
      Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
FAU - Molteni, Raffaella
AU  - Molteni R
AD  - Department of Medical Biotechnology and Translational Medicine, University of 
      Milan, Milan, Italy.
FAU - Riva, Marco A
AU  - Riva MA
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan, 
      Milan, Italy.
FAU - Van der Harst, Johanneke E
AU  - Van der Harst JE
AD  - Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive 
      Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
AD  - Noldus Information Technology BV, Wageningen, The Netherlands.
FAU - Nguyen, Huu Phuc
AU  - Nguyen HP
AUID- ORCID: 0000-0001-6139-788X
AD  - Institute of Medical Genetics and Applied Genomics, University of Tubingen, 
      Tubingen, Germany.
AD  - Centre of Rare Diseases, University of Tubingen, Tubingen, Germany.
FAU - Homberg, Judith R
AU  - Homberg JR
AD  - Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive 
      Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180207
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Htt protein, rat)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, Dopamine D2)
SB  - IM
MH  - Animals
MH  - *Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Corpus Striatum/metabolism
MH  - *Disease Models, Animal
MH  - Huntingtin Protein/*genetics
MH  - Huntington Disease/*physiopathology
MH  - *Mutation
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Dopamine D1/genetics
MH  - Receptors, Dopamine D2/genetics
MH  - *Social Behavior
PMC - PMC5802907
COIS- Competing Interests: At the time of the studies the authors G. Manfre and Dr. 
      J.E. van der Harst were working for the EU funded "PhenoRat" project of which 
      Noldus Information Technology was an industrial partner. Dr. J.E. van der Harst 
      was part-time scientific project advisor for "PhenoRat" employed by Noldus 
      Information Technology. Dr. A. Novati was working at the University of Tuebingen 
      for the EU funded "Switch HD" project of which QPS Austria was an industrial 
      partner. Noldus Information Technology and QPS Austria had no role in study 
      design, data collection and analysis, decision to publish, or preparation of the 
      manuscript. G. Manfre and Dr. J.E. van der Harst's involvement in the current 
      study should thus be considered the work of independent researchers, rather than 
      representatives of a commercial company. There are no patents, products in 
      development, or marketed products to declare. This does not alter the authors' 
      adherence to PLOS ONE policies on sharing data and materials.
EDAT- 2018/02/08 06:00
MHDA- 2018/04/13 06:00
PMCR- 2018/02/07
CRDT- 2018/02/08 06:00
PHST- 2017/08/01 00:00 [received]
PHST- 2018/01/22 00:00 [accepted]
PHST- 2018/02/08 06:00 [entrez]
PHST- 2018/02/08 06:00 [pubmed]
PHST- 2018/04/13 06:00 [medline]
PHST- 2018/02/07 00:00 [pmc-release]
AID - PONE-D-17-28586 [pii]
AID - 10.1371/journal.pone.0192289 [doi]
PST - epublish
SO  - PLoS One. 2018 Feb 7;13(2):e0192289. doi: 10.1371/journal.pone.0192289. 
      eCollection 2018.