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Diet-induced hyperhomocysteinemia causes sex-dependent deficiencies in offspring musculature and brain function

cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid0000-0002-0791-5057
cris.virtual.author-orcid0000-0001-5845-4409
cris.virtualsource.author-orcidf22f1799-d4c9-4523-90d4-f2f2bc6eab63
cris.virtualsource.author-orcid9cfa7201-4c9c-4918-bd81-a322bae987fe
cris.virtualsource.author-orcid06f046d1-df27-46e5-abe5-17d98aeed726
cris.virtualsource.author-orcid4dde7a12-8c22-4e89-9d57-7c74b050ccc5
dc.abstract.enHyperhomocysteinemia (HHcy), characterized by elevated homocysteine (Hcy) levels, is a known risk factor for cardiovascular, renal, and neurological diseases, as well as pregnancy complications. Our study aimed to investigate whether HHcy induced by a high-methionine (high-Met) diet exacerbates cognitive and behavioral deficits in offspring and leads to other breeding problems. Dietary HHcy was induced four weeks before mating and continued throughout gestation and post-delivery. A battery of behavioral tests was conducted on offspring between postnatal days (PNDs) 5 and 30 to assess motor function/ activity and cognition. The results were correlated with brain morphometric measurements and quantitative analysis of mammalian target of rapamycin (mTOR)/autophagy markers. The high-Met diet significantly increased parental and offspring urinary tHcy levels and influenced offspring behavior in a sexdependent manner. Female offspring exhibited impaired cognition, potentially related to morphometric changes observed exclusively in HHcy females. Male HHcy pups demonstrated muscle weakness, evidenced by slower surface righting, reduced hind limb suspension (HLS) hanging time, weaker grip strength, and decreased activity in the beaker test. Western blot analyses indicated the downregulation of autophagy and the upregulation of mTOR activity in HHcy cortexes. HHcy also led to breeding impairments, including reduced breeding rate, in-utero fetal death, lower pups’ body weight, and increased mortality, likely attributed to placental dysfunction associated with HHcy. In conclusion, a high-Met diet impairs memory and cognition in female juveniles and weakens muscle strength in male pups. These effects may stem from abnormal placental function affecting early neurogenesis, the dysregulation of autophagy-related pathways in the cortex, or epigenetic mechanisms of gene regulation triggered by HHcy during embryonic development
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Biotechnologii
dc.affiliation.instituteKatedra Biochemii i Biotechnologii
dc.contributor.authorSuszyńska-Zajczyk, Joanna
dc.contributor.authorWitucki, Łukasz
dc.contributor.authorPerła-Kajan, Joanna
dc.contributor.authorJakubowski, Hieronim
dc.date.access2024-10-16
dc.date.accessioned2024-10-29T08:04:23Z
dc.date.available2024-10-29T08:04:23Z
dc.date.copyright2024-03-15
dc.date.issued2024
dc.description.abstract<jats:p>Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine (Hcy) levels, is a known risk factor for cardiovascular, renal, and neurological diseases, as well as pregnancy complications. Our study aimed to investigate whether HHcy induced by a high-methionine (high-Met) diet exacerbates cognitive and behavioral deficits in offspring and leads to other breeding problems. Dietary HHcy was induced four weeks before mating and continued throughout gestation and post-delivery. A battery of behavioral tests was conducted on offspring between postnatal days (PNDs) 5 and 30 to assess motor function/activity and cognition. The results were correlated with brain morphometric measurements and quantitative analysis of mammalian target of rapamycin (mTOR)/autophagy markers. The high-Met diet significantly increased parental and offspring urinary tHcy levels and influenced offspring behavior in a sex-dependent manner. Female offspring exhibited impaired cognition, potentially related to morphometric changes observed exclusively in HHcy females. Male HHcy pups demonstrated muscle weakness, evidenced by slower surface righting, reduced hind limb suspension (HLS) hanging time, weaker grip strength, and decreased activity in the beaker test. Western blot analyses indicated the downregulation of autophagy and the upregulation of mTOR activity in HHcy cortexes. HHcy also led to breeding impairments, including reduced breeding rate, in-utero fetal death, lower pups’ body weight, and increased mortality, likely attributed to placental dysfunction associated with HHcy. In conclusion, a high-Met diet impairs memory and cognition in female juveniles and weakens muscle strength in male pups. These effects may stem from abnormal placental function affecting early neurogenesis, the dysregulation of autophagy-related pathways in the cortex, or epigenetic mechanisms of gene regulation triggered by HHcy during embryonic development.</jats:p>
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0.00
dc.description.if4,6
dc.description.points100
dc.description.versionfinal_published
dc.description.volume12
dc.identifier.doi10.3389/fcell.2024.1322844
dc.identifier.eissn2296-634X
dc.identifier.issn2296-634X
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/1946
dc.identifier.weblinkhttps://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1322844/full
dc.languageen
dc.relation.ispartofFrontiers in Cell and Developmental Biology
dc.relation.pagesart. 1322844
dc.rightsCC-BY
dc.sciencecloudsend
dc.share.typeOPEN_JOURNAL
dc.subject.enhyperhomocysteinemia
dc.subject.enpregnancy outcomes
dc.subject.enoffspring
dc.subject.enhigh-Met diet
dc.subject.enbehavior and cognition
dc.titleDiet-induced hyperhomocysteinemia causes sex-dependent deficiencies in offspring musculature and brain function
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.volume12