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

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Fältnamn	Indikatorer	Metadata
000		05938naa a2200421 4500
001		oai:lup.lub.lu.se:a5309640-03a5-4120-bf31-0d11524d58f8
003		SwePub
008		230802s2023 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/a5309640-03a5-4120-bf31-0d11524d58f82 URI
024	7	a https://doi.org/10.1016/j.bbih.2023.1006632 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Garcia, M.g.u Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups4 aut0 (Swepub:lu)me5408ga
245	1 0	a Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer’s disease-transgenic mice
264	1	c 2023
300		a 10 s.
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
653		a Alzheimer's disease
653		a Amyloid-β
653		a Early-life stress
653		a Maternal separation
653		a Neuroinflammation
700	1	a Paulus, A.u 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 areas4 aut0 (Swepub:lu)ag5431pa
700	1	a Vázquez-Reyes, S.u Lund University4 aut
700	1	a Klementieva, O.u 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 areas4 aut0 (Swepub:lu)med-oka
700	1	a Gouras, G.k.u Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups4 aut0 (Swepub:lu)med-grg
700	1	a Bachiller, S.u Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,University of Seville4 aut0 (Swepub:lu)sa2870ba
700	1	a Deierborg, T.u 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 Groups4 aut0 (Swepub:lu)expb-tol
710	2	a Neuroinflammationb Forskargrupper vid Lunds universitet4 org
773	0	t Brain, Behavior, & Immunity - Healthg 32q 32x 2666-3546
856	4	u http://dx.doi.org/10.1016/j.bbih.2023.100663x freey FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/a5309640-03a5-4120-bf31-0d11524d58f8
856	4 8	u https://doi.org/10.1016/j.bbih.2023.100663

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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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