title: Peripheral Levels of AGEs and Astrocyte Alterations in the Hippocampus of STZ-Diabetic Rats.
abstract: Diabetic patients and streptozotocin (STZ)-induced diabetes mellitus (DM) models exhibit signals of brain dysfunction, evidenced by neuronal damage and memory impairment. Astrocytes surrounding capillaries and synapses modulate many brain activities that are connected to neuronal function, such as nutrient flux and glutamatergic neurotransmission. As such, cognitive changes observed in diabetic patients and experimental models could be related to astroglial alterations. Herein, we investigate specific astrocyte changes in the rat hippocampus in a model of DM induced by STZ, particularly looking at glial fibrillary acidic protein (GFAP), S100B protein and glutamate uptake, as well as the content of advanced glycated end products (AGEs) in serum and cerebrospinal fluid (CSF), as a consequence of elevated hyperglycemia and the content of receptor for AGEs in the hippocampus. We found clear peripheral alterations, including hyperglycemia, low levels of proinsulin C-peptide, elevated levels of AGEs in serum and CSF, as well as an increase in RAGE in hippocampal tissue. We found specific astroglial abnormalities in this brain region, such as reduced S100B content, reduced glutamate uptake and increased S100B secretion, which were not accompanied by changes in GFAP. We also observed an increase in the glucose transporter, GLUT-1. All these changes may result from RAGE-induced inflammation; these astroglial alterations together with the reduced content of GluN1, a subunit of the NMDA receptor, in the hippocampus may be associated with the impairment of glutamatergic communication in diabetic rats. These findings contribute to understanding the cognitive deficits in diabetic patients and experimental models.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil. patricianardin@gmail.com.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nardin
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zanotto
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Hansen
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Batassini
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Manuela Sangalli
authors.initials: MS
authors.lastname: Gasparin
authors.affiliation: Centro de Desenvolvimento Científico e Tecnológico, Fundação Estadual de Produção e Pesquisa em Saúde, Porto Alegre, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Sesterheim
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011921:Rats, Inbred WKY; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D013311:Streptozocin
keywords: Advanced glycation end products (AGEs); Diabetes mellitus; GFAP; Glutamate neurotransmission; S100B secretion