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Standardized Bacopa monnieri Extract Ameliorates Learning and Memory Impairments through Synaptic Protein, Neurogranin, Pro-and Mature BDNF Signaling, and HPA Axis in Prenatally Stressed Rat Offspring.

ABSTRACT: Prenatal stress (PNS) influences offspring neurodevelopment, inducing anxiety-like behavior and memory deficits. We investigated whether pretreatment of Bacopa monnieri extract (CDRI-08/BME) ameliorates PNS-induced changes in signaling molecules, and changes in the behavior of Wistar rat offspring. Pregnant rats were randomly assigned into control (CON)/prenatal stress (PNS)/PNS and exposed to BME treatment (PNS + BME). Dams were exposed to stress by placing them in a social defeat cage, where they observed social defeat from gestational day (GD)-16-18. Pregnant rats in the PNS + BME group were given BME treatment from GD-10 to their offspring's postnatal day (PND)-23, and to their offspring from PND-15 to -30. PNS led to anxiety-like behavior; impaired memory; increased the level of corticosterone (CORT), adrenocorticotropic hormone, glucocorticoid receptor, pro-apoptotic Casepase-3, and 5-HT_2C receptor; decreased anti-apoptotic Bcl-2, synaptic proteins (synaptophysin, synaptotagmin-1), 5-HT_1A, receptor, phosphorylation of calmodulin-dependent protein kinase II/neurogranin, N-methyl-D-aspartate receptors (2A,2B), postsynaptic density protein 95; and conversion of pro and mature brain derived neurotropic factor in their offspring. The antioxidant property of BME possibly inhibiting the PNS-induced changes in observed molecules, anxiety-like behavior, and memory deficits. The observed results suggest that pretreatment of BME could be an effective coping strategy to prevent PNS-induced behavioral impairments in their offspring.

SUBMITTER: Sivasangari K

PROVIDER: S-EPMC7761874 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Standardized <i>Bacopa monnieri</i> Extract Ameliorates Learning and Memory Impairments through Synaptic Protein, Neurogranin, Pro-and Mature BDNF Signaling, and HPA Axis in Prenatally Stressed Rat Offspring.

Sivasangari Karunanithi K Rajan Koilmani Emmanuvel KE

Antioxidants (Basel, Switzerland) 20201204 12

Prenatal stress (PNS) influences offspring neurodevelopment, inducing anxiety-like behavior and memory deficits. We investigated whether pretreatment of <i>Bacopa monnieri</i> extract (CDRI-08/BME) ameliorates PNS-induced changes in signaling molecules, and changes in the behavior of Wistar rat offspring. Pregnant rats were randomly assigned into control (CON)/prenatal stress (PNS)/PNS and exposed to BME treatment (PNS + BME). Dams were exposed to stress by placing them in a social defeat cage, ...[more]

PMID: 33291595

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Project description:Ethnopharmacological relevanceBacopa monnieri (L) Wettst (common name, bacopa) is a medicinal plant used in Ayurveda, the traditional system of medicine of India, as a nootropic. It is considered to be a "medhya rasayana", an herb that sharpens the mind and the intellect. Bacopa is an important ingredient in many Ayurvedic herbal formulations designed to treat conditions such as memory loss, anxiety, poor cognition and loss of concentration. It has also been used in Ayurveda to treat inflammatory conditions such as arthritis. In modern biomedical studies, bacopa has been shown in animal models to inhibit the release of the pro-inflammatory cytokines TNF-α and IL-6. However, less is known regarding the anti-inflammatory activity of Bacopa in the brain.Aim of the studyThe current study examines the ability of Bacopa to inhibit the release of pro-inflammatory cytokines from microglial cells, the immune cells of the brain that participate in inflammation in the CNS. The effect of Bacopa on signaling enzymes associated with CNS inflammatory pathways was also studied.Materials and methodsVarious extracts of Bacopa were prepared and examined in the N9 microglial cell line in order to determine if they inhibited the release of the proinflammatory cytokines TNF-α and IL-6. Extracts were also tested in cell free assays as inhibitors of caspase-1 and matrix metalloproteinase-3 (enzymes associated with inflammation) and caspase-3, which has been shown to cleave protein Tau, an early event in the development of Alzheimer's disease.ResultsThe tea, infusion, and alkaloid extracts of bacopa, as well as Bacoside A significantly inhibited the release of TNF-α and IL-6 from activated N9 microglial cells in vitro. In addition, the tea, infusion, and alkaloid extracts of Bacopa effectively inhibited caspase 1 and 3, and matrix metalloproteinase-3 in the cell free assay.ConclusionsBacopa inhibits the release of inflammatory cytokines from microglial cells and inhibits enzymes associated with inflammation in the brain. Thus, Bacopa can limit inflammation in the CNS, and offers a promising source of novel therapeutics for the treatment of many CNS disorders.

Dataset Information

Standardized Bacopa monnieri Extract Ameliorates Learning and Memory Impairments through Synaptic Protein, Neurogranin, Pro-and Mature BDNF Signaling, and HPA Axis in Prenatally Stressed Rat Offspring.

Publications

Standardized <i>Bacopa monnieri</i> Extract Ameliorates Learning and Memory Impairments through Synaptic Protein, Neurogranin, Pro-and Mature BDNF Signaling, and HPA Axis in Prenatally Stressed Rat Offspring.

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