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Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner

Bachiller, S. (author)
Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
Hidalgo, I. (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine
Garcia, M. G. (author)
Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Neuroinflammation,Experimental Dementia Research,Lund University Research Groups
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Boza-Serrano, A. (author)
Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,University of Seville
Paulus, A. (author)
Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Neuroinflammation,Forskargrupper vid Lunds universitet,Medicinsk mikrospektroskopi,Other operations, LTH,Faculty of Engineering, LTH,Lund University Research Groups,Medical Microspectroscopy
Denis, Q. (author)
Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
Haikal, C. (author)
Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Neural Plasticity and Repair,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
Manouchehrian, O. (author)
Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
Klementieva, O. (author)
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,Other operations, LTH,Faculty of Engineering, LTH,Medical Microspectroscopy,Lund University Research Groups,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
Li, J. Y. (author)
Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups
Pronk, C. J. (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,WCMM- Wallenberg center för molekylär medicinsk forskning,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,WCMM-Wallenberg Centre for Molecular Medicine
Gouras, G. K. (author)
Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups
Deierborg, T. (author)
Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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 (creator_code:org_t)
2022-06-15
2022
English.
In: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 19
Related links:
http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • BackgroundThe risk of developing Alzheimer’s disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD.MethodsHere, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS.ResultsWe detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure.ConclusionOverall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

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