Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer’s disease-transgenic mice

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Garcia, M.g.Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups (författare)

Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer’s disease-transgenic mice

Artikel/kapitelEngelska2023

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2023
10 s.

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LIBRIS-ID:oai:lup.lub.lu.se:a5309640-03a5-4120-bf31-0d11524d58f8
https://lup.lub.lu.se/record/a5309640-03a5-4120-bf31-0d11524d58f8URI
https://doi.org/10.1016/j.bbih.2023.100663DOI

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Språk:engelska
Sammanfattning på:engelska

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Alzheimer’s disease (AD) is the most common neurodegenerative disease. Most cases of AD are considered idiopathic and likely due to a combination of genetic, environmental, and lifestyle-related risk factors. Despite occurring decades before the typical age of an AD diagnosis, early-life stress (ELS) has been suggested to have long-lasting effects that may contribute to AD risk and pathogenesis. Still, the mechanisms that underlie the role of ELS on AD risk remain largely unknown. Here, we used 5xFAD transgenic mice to study relatively short-term alterations related to ELS in an AD-like susceptible mouse model at 6 weeks of age. To model ELS, we separated pups from their dams for 3 h per day from postnatal day 2–14. Around 6 weeks of age, we found that maternally separated (MS) 5xFAD mice, particularly female mice, displayed increased amyloid-β-immunoreactivity in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). In anterior cingulate cortex, we also noted significantly increased intraneuronal amyloid-β-immunoreactivity associated with MS but only in female mice. Moreover, IBA1-positive DAPI density was significantly increased in relation to MS in ACC and BLA, and microglia in BLA of MS mice had significantly different morphology compared to microglia in non-MS 5xFAD mice. Cytokine analysis showed that male MS mice, specifically, had increased levels of neuroinflammatory markers CXCL1 and IL-10 in hippocampal extracts compared to non-MS counterparts. Additionally, hippocampal extracts from both male and female MS 5xFAD mice had decreased levels of synapse- and activity-related markers Bdnf, 5htr6, Cox2, and Syp in hippocampus. Lastly, we performed behavioral tests to evaluate anxiety- and depressive-like behavior and working memory but could not detect any significant differences between groups. Overall, we detected several sex-specific molecular and cellular alterations in 6-week-old adolescent 5xFAD mice associated with MS that may help explain the connection between ELS and AD risk.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Alzheimer's disease
Amyloid-β
Early-life stress
Maternal separation
Neuroinflammation

Biuppslag (personer, institutioner, konferenser, titlar ...)

Paulus, A.Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Medicinsk mikrospektroskopi,Forskargrupper vid Lunds universitet,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Medical Microspectroscopy,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas(Swepub:lu)ag5431pa (författare)
Vázquez-Reyes, S.Lund University (författare)
Klementieva, O.Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Medicinsk mikrospektroskopi,Forskargrupper vid Lunds universitet,LINXS - Institute of advanced Neutron and X-ray Science,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Medical Microspectroscopy,Lund University Research Groups,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas(Swepub:lu)med-oka (författare)
Gouras, G.k.Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups(Swepub:lu)med-grg (författare)
Bachiller, S.Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,University of Seville(Swepub:lu)sa2870ba (författare)
Deierborg, T.Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Neuroinflammation,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Lund University Research Groups(Swepub:lu)expb-tol (författare)
NeuroinflammationForskargrupper vid Lunds universitet (creator_code:org_t)

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Ingår i:Brain, Behavior, & Immunity - Health322666-3546

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Av författaren/redakt...: Garcia, M.g.; Paulus, A.; Vázquez-Reyes, S ...; Klementieva, O.; Gouras, G.k.; Bachiller, S.; visa fler...; Deierborg, T.; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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Av lärosätet: Lunds universitet

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