Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Resveratrol prevents long-term structural hippocampal alterations and modulates interneuron organization in an animal model of ASD
AU - Santos-Terra, Júlio
AU - Deckmann, Iohanna
AU - Schwingel, Gustavo Brum
AU - Paz, André Vinicius Contri
AU - Gama, Clarissa S
AU - Bambini-Junior, Victorio
AU - Fontes-Dutra, Mellanie
AU - Gottfried, Carmem
N1 - Copyright © 2021 Elsevier B.V. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in both communication and social interaction, besides repetitive or stereotyped behavior. Although the etiology is unknown, environmental factors such as valproic acid (VPA) increase the risk of ASD onset. Resveratrol (RSV), a neuroprotective molecule, has been shown to counteract the effects of intrauterine exposure to VPA. We aimed to evaluate histological parameters related to hippocampal morphology and to the distribution of parvalbumin- (PV), calbindin- (CB), and somatostatin-positive (SOM) interneurons sub-populations, in addition to evaluate the total/phosphorylation levels of PTEN, AKT, GSK3β and total CK2 in the animal model of autism induced by VPA, as well as addressing the potential protective effect of RSV. On postnatal day 120, histological analysis showed a loss in total neurons in the dentate gyrus (DG) and decreased CB+ neurons in DG and CA1 in VPA animals, both prevented by RSV. In addition, PV+ neurons were diminished in CA1, CA2, and CA3, and SOM+ were interestingly increased in DG (prevented by RSV) and decreased in CA1 and CA2. A hippocampal lesion similar to sclerosis was also observed in the samples from the VPA group. Besides that, VPA reduced AKT and PTEN immunocontent, and VPA increased CK2 immunocontent. Thus, this work demonstrated long-term effects of prenatal exposure to ASD in different sub-populations of interneurons, structural damage of hippocampus, and also alteration in proteins associated with pivotal cell signaling pathways, highlighting the role of RSV as a tool for understanding the pathophysiology of ASD.
AB - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in both communication and social interaction, besides repetitive or stereotyped behavior. Although the etiology is unknown, environmental factors such as valproic acid (VPA) increase the risk of ASD onset. Resveratrol (RSV), a neuroprotective molecule, has been shown to counteract the effects of intrauterine exposure to VPA. We aimed to evaluate histological parameters related to hippocampal morphology and to the distribution of parvalbumin- (PV), calbindin- (CB), and somatostatin-positive (SOM) interneurons sub-populations, in addition to evaluate the total/phosphorylation levels of PTEN, AKT, GSK3β and total CK2 in the animal model of autism induced by VPA, as well as addressing the potential protective effect of RSV. On postnatal day 120, histological analysis showed a loss in total neurons in the dentate gyrus (DG) and decreased CB+ neurons in DG and CA1 in VPA animals, both prevented by RSV. In addition, PV+ neurons were diminished in CA1, CA2, and CA3, and SOM+ were interestingly increased in DG (prevented by RSV) and decreased in CA1 and CA2. A hippocampal lesion similar to sclerosis was also observed in the samples from the VPA group. Besides that, VPA reduced AKT and PTEN immunocontent, and VPA increased CK2 immunocontent. Thus, this work demonstrated long-term effects of prenatal exposure to ASD in different sub-populations of interneurons, structural damage of hippocampus, and also alteration in proteins associated with pivotal cell signaling pathways, highlighting the role of RSV as a tool for understanding the pathophysiology of ASD.
KW - Animals
KW - Autism Spectrum Disorder/drug therapy
KW - Behavior, Animal/drug effects
KW - Disease Models, Animal
KW - Female
KW - Hippocampus/drug effects
KW - Interneurons/drug effects
KW - Male
KW - Neurons/metabolism
KW - Pregnancy
KW - Prenatal Exposure Delayed Effects/physiopathology
KW - Rats, Wistar
KW - Resveratrol/metabolism
KW - Social Behavior
KW - Stereotyped Behavior/drug effects
KW - Valproic Acid/pharmacology
U2 - 10.1016/j.brainres.2021.147593
DO - 10.1016/j.brainres.2021.147593
M3 - Journal article
C2 - 34331907
VL - 1768
JO - Brain Research
JF - Brain Research
SN - 0006-8993
M1 - 147593
ER -