Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease

Várkonyi, Dorottya [Várkonyi, Dorottya (Neurobiológia), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); Török, Bibiána* [Szocsics-Török, Bibiána (Biológus), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Sipos, Eszter [Bodóné Sipos, Eszter (Idegtudomány), author] Laboratory of Behavioural and Stress Studies (IEM / DBN); Institute of Experimental Medicine; Fazekas, Csilla Lea [Fazekas, Csilla Lea (Neurobiológia), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Bánrévi, Krisztina; Correia, Pedro [Correia, Pedro (Neuroscience), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Chaves, Tiago [Chaves, Tiago (Orvostudomány), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Farkas, Szidónia [Farkas, Szidónia (Gyógyszerészet), author] Institute of Physiology (UP / UPMS); Molecular nNeuroendocrinology Research Group (UP / SZRC); Szabó, Adrienn [Szabó, Adrienn (Sejtbiológia), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); School of PhD Studies (SU); Martínez-Bellver, Sergio [Martínez-Bellver, Sergio (neurobiológia), author] Laboratory of System-Neurobiology; Hangya, Balázs [Hangya, Balázs (Neurobiológia), author] Institute of Experimental Medicine; Laboratory of System-Neurobiology; Zelena, Dóra ✉ [Zelena, Dóra (Neuroendokrinológia), author] Institute of Physiology (UP / UPMS); Szentágothai Research Centre (UP); Laboratory of Behavioural and Stress Studies (IEM / DBN)

English Article (Journal Article) Scientific
Published: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 1661-6596 1422-0067 23 (18) Paper: 10816 , 22 p. 2022
  • SJR Scopus - Inorganic Chemistry: D1
Identifiers
Fundings:
  • (K141934) Funder: NRDIO
  • (K138763) Funder: NKFIH
  • (K120311) Funder: NKFIH
  • (TKP2021-EGA-16)
Subjects:
  • Neurological disorders (e.g. Alzheimer's disease, Huntington's disease, Parkinson's disease)
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Approximately 50% of AD patients show anxiety and depressive symptoms, which may contribute to cognitive decline. We aimed to investigate whether the triple-transgenic mouse (3xTg-AD) is a good preclinical model of this co-morbidity. The characteristic histological hallmarks are known to appear around 6-month; thus, 4- and 8-month-old male mice were compared with age-matched controls. A behavioral test battery was used to examine anxiety- (open field (OF), elevated plus maze, light-dark box, novelty suppressed feeding, and social interaction (SI) tests), and depression-like symptoms (forced swim test, tail suspension test, sucrose preference test, splash test, and learned helplessness) as well as the cognitive decline (Morris water maze (MWM) and social discrimination (SD) tests). Acetylcholinesterase histochemistry visualized cholinergic fibers in the cortex. Dexamethasone-test evaluated the glucocorticoid non-suppression. In the MWM, the 3xTg-AD mice found the platform later than controls in the 8-month-old cohort. The SD abilities of the 3xTg-AD mice were missing at both ages. In OF, both age groups of 3xTg-AD mice moved significantly less than the controls. During SI, 8-month-old 3xTg-AD animals spent less time with friendly social behavior than the controls. In the splash test, 3xTg-AD mice groomed themselves significantly less than controls of both ages. Cortical fiber density was lower in 8-month-old 3xTg-AD mice compared to the control. Dexamethasone non-suppression was detectable in the 4-month-old group. All in all, some anxiety- and depressive-like symptoms were present in 3xTg-AD mice. Although this strain was not generally more anxious or depressed, some aspects of comorbidity might be studied in selected tests, which may help to develop new possible treatments.
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2026-01-14 18:37