Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2
Social withdrawal and deficits in social cognition are hallmarks of Alzheimer's disease (AD). While early deficits in social behavior and memory have been documented in mouse AD models, they remain understudied in rat models. Early-stage AD is accompanied by dysfunction of parvalbumin-positive...
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Elsevier
2025-05-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000919 |
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| author | Daniela Černotová Karolína Hrůzová Jan Touš Radek Janča Aleš Stuchlík David Levčík Jan Svoboda |
| author_facet | Daniela Černotová Karolína Hrůzová Jan Touš Radek Janča Aleš Stuchlík David Levčík Jan Svoboda |
| author_sort | Daniela Černotová |
| collection | DOAJ |
| description | Social withdrawal and deficits in social cognition are hallmarks of Alzheimer's disease (AD). While early deficits in social behavior and memory have been documented in mouse AD models, they remain understudied in rat models. Early-stage AD is accompanied by dysfunction of parvalbumin-positive (PV+) interneurons, implicating their potential connection to early symptoms. In this study, we employed a 5-trial social memory task to investigate early deficits in social cognition in 6-month-old TgF344-AD male and female rats. We counted the number of PV+ interneurons and recorded local field potentials during social interactions in the hippocampal CA2 – a region critical for social information processing. Our results show decreased social interest and novelty preference in TgF344-AD male and female rats. However, reduced PV+ interneuron numbers were observed only in female rats and specific to the CA2 area. The electrophysiological recordings revealed reduced theta-gamma phase-amplitude coupling in the CA2 during direct social interactions. We conclude that deficits in social cognition accompany early-stage AD in TgF344-AD rats and are potentially linked to PV+ interneuron and brain oscillatory dysfunction in the CA2 region of the hippocampus. |
| format | Article |
| id | doaj-art-4e8009f06e1b4b539b379e398a5d18e1 |
| institution | DOAJ |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-4e8009f06e1b4b539b379e398a5d18e12025-08-20T03:08:47ZengElsevierNeurobiology of Disease1095-953X2025-05-0120810687510.1016/j.nbd.2025.106875Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2Daniela Černotová0Karolína Hrůzová1Jan Touš2Radek Janča3Aleš Stuchlík4David Levčík5Jan Svoboda6Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech Republic; Third Faculty of Medicine, Charles University, Ruska 87, Prague 100 00, Czech RepublicLaboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech Republic; Third Faculty of Medicine, Charles University, Ruska 87, Prague 100 00, Czech RepublicLaboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech Republic; Faculty of Electrical Engineering, Czech Technical University in Prague, Technicka 2, Prague 160 00, Czech RepublicFaculty of Electrical Engineering, Czech Technical University in Prague, Technicka 2, Prague 160 00, Czech RepublicLaboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech RepublicLaboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech Republic; Corresponding author.Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech RepublicSocial withdrawal and deficits in social cognition are hallmarks of Alzheimer's disease (AD). While early deficits in social behavior and memory have been documented in mouse AD models, they remain understudied in rat models. Early-stage AD is accompanied by dysfunction of parvalbumin-positive (PV+) interneurons, implicating their potential connection to early symptoms. In this study, we employed a 5-trial social memory task to investigate early deficits in social cognition in 6-month-old TgF344-AD male and female rats. We counted the number of PV+ interneurons and recorded local field potentials during social interactions in the hippocampal CA2 – a region critical for social information processing. Our results show decreased social interest and novelty preference in TgF344-AD male and female rats. However, reduced PV+ interneuron numbers were observed only in female rats and specific to the CA2 area. The electrophysiological recordings revealed reduced theta-gamma phase-amplitude coupling in the CA2 during direct social interactions. We conclude that deficits in social cognition accompany early-stage AD in TgF344-AD rats and are potentially linked to PV+ interneuron and brain oscillatory dysfunction in the CA2 region of the hippocampus.http://www.sciencedirect.com/science/article/pii/S0969996125000919Alzheimer's diseaseTgF344-ADSocial memoryCA2HippocampusParvalbumin-positive interneurons |
| spellingShingle | Daniela Černotová Karolína Hrůzová Jan Touš Radek Janča Aleš Stuchlík David Levčík Jan Svoboda Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2 Neurobiology of Disease Alzheimer's disease TgF344-AD Social memory CA2 Hippocampus Parvalbumin-positive interneurons |
| title | Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2 |
| title_full | Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2 |
| title_fullStr | Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2 |
| title_full_unstemmed | Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2 |
| title_short | Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2 |
| title_sort | early social deficits in tgf344 ad rats are accompanied by sex specific parvalbumin positive interneuron reduction and altered brain oscillations in the hippocampal ca2 |
| topic | Alzheimer's disease TgF344-AD Social memory CA2 Hippocampus Parvalbumin-positive interneurons |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000919 |
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