In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease
Astrocytes play fundamental roles in the maintenance of brain homeostasis. The dysfunction of these cells is widely associated with brain disorders, which are often characterized by variations in the astrocyte protein markers GFAP and S100B, in addition to alterations in some of its metabolic functi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/14/3/151 |
| _version_ | 1827305642306568192 |
|---|---|
| author | Jéssica Taday Fernanda Telles Fróes Marina Seady Carlos Alberto Gonçalves Marina Concli Leite |
| author_facet | Jéssica Taday Fernanda Telles Fróes Marina Seady Carlos Alberto Gonçalves Marina Concli Leite |
| author_sort | Jéssica Taday |
| collection | DOAJ |
| description | Astrocytes play fundamental roles in the maintenance of brain homeostasis. The dysfunction of these cells is widely associated with brain disorders, which are often characterized by variations in the astrocyte protein markers GFAP and S100B, in addition to alterations in some of its metabolic functions. To understand the role of astrocytes in neurodegeneration mechanisms, we induced some of these metabolic alterations, such as energy metabolism, using methylglyoxal (MG) or fluorocitrate (FC); and neuroinflammation, using lipopolysaccharide (LPS) and streptozotocin (STZ), which is used for inducing Alzheimer’s disease (AD) in animal models. We showed that MG, LPS, STZ and FC similarly caused astrocyte dysfunction by increasing GFAP and reducing S100B secretion. In the context of AD, STZ caused an amyloid metabolism impairment verified by increases in Aβ1-40 peptide content and decreases in the amyloid degradation enzymes, IDE and NEP. Our data contribute to the understanding of the role of astrocytes in brain injury mechanisms and suggest that STZ is suitable for use in vitro models for studying the role of astrocytes in AD. |
| first_indexed | 2024-04-24T18:01:36Z |
| format | Article |
| id | doaj.art-74c4f9a7c51f4857b23599194b101956 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-04-24T18:01:36Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-74c4f9a7c51f4857b23599194b1019562024-03-27T13:54:08ZengMDPI AGMetabolites2218-19892024-03-0114315110.3390/metabo14030151In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s DiseaseJéssica Taday0Fernanda Telles Fróes1Marina Seady2Carlos Alberto Gonçalves3Marina Concli Leite4Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, BrazilDepartamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, BrazilDepartamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, BrazilDepartamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, BrazilDepartamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, BrazilAstrocytes play fundamental roles in the maintenance of brain homeostasis. The dysfunction of these cells is widely associated with brain disorders, which are often characterized by variations in the astrocyte protein markers GFAP and S100B, in addition to alterations in some of its metabolic functions. To understand the role of astrocytes in neurodegeneration mechanisms, we induced some of these metabolic alterations, such as energy metabolism, using methylglyoxal (MG) or fluorocitrate (FC); and neuroinflammation, using lipopolysaccharide (LPS) and streptozotocin (STZ), which is used for inducing Alzheimer’s disease (AD) in animal models. We showed that MG, LPS, STZ and FC similarly caused astrocyte dysfunction by increasing GFAP and reducing S100B secretion. In the context of AD, STZ caused an amyloid metabolism impairment verified by increases in Aβ1-40 peptide content and decreases in the amyloid degradation enzymes, IDE and NEP. Our data contribute to the understanding of the role of astrocytes in brain injury mechanisms and suggest that STZ is suitable for use in vitro models for studying the role of astrocytes in AD.https://www.mdpi.com/2218-1989/14/3/151astrocytesAlzheimer’s diseasestreptozotocinlipopolysaccharidefluorocitratemethylglyoxal |
| spellingShingle | Jéssica Taday Fernanda Telles Fróes Marina Seady Carlos Alberto Gonçalves Marina Concli Leite In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease Metabolites astrocytes Alzheimer’s disease streptozotocin lipopolysaccharide fluorocitrate methylglyoxal |
| title | In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease |
| title_full | In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease |
| title_fullStr | In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease |
| title_full_unstemmed | In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease |
| title_short | In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease |
| title_sort | in vitro astroglial dysfunction induced by neurotoxins mimicking astrocytic metabolic alterations of alzheimer s disease |
| topic | astrocytes Alzheimer’s disease streptozotocin lipopolysaccharide fluorocitrate methylglyoxal |
| url | https://www.mdpi.com/2218-1989/14/3/151 |
| work_keys_str_mv | AT jessicataday invitroastroglialdysfunctioninducedbyneurotoxinsmimickingastrocyticmetabolicalterationsofalzheimersdisease AT fernandatellesfroes invitroastroglialdysfunctioninducedbyneurotoxinsmimickingastrocyticmetabolicalterationsofalzheimersdisease AT marinaseady invitroastroglialdysfunctioninducedbyneurotoxinsmimickingastrocyticmetabolicalterationsofalzheimersdisease AT carlosalbertogoncalves invitroastroglialdysfunctioninducedbyneurotoxinsmimickingastrocyticmetabolicalterationsofalzheimersdisease AT marinaconclileite invitroastroglialdysfunctioninducedbyneurotoxinsmimickingastrocyticmetabolicalterationsofalzheimersdisease |