Rafael Roehrs

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

Significance A brief exposure to a novel environment was recently shown to enhance the extinction of contextual fear probably through a protein synthesis-dependent process of synaptic tagging and capture in the hippocampus. Here we report that this finding can be generalized to the extinction of another fear-motivated task, one-trial inhibitory avoidance. This generalization is important because extinction is used in exposure therapy to treat posttraumatic stress disorder in humans, and this may derive from various forms of fear-related stress. In addition, here we show that the effect of novelty on fear extinction is dependent on dopamine D1 but not D5 receptors in the hippocampus. These findings could be applicable to the exposure therapy of fear memory disorders. Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.

Hippocampal noradrenergic activation is necessary for object recognition memory consolidation and can promote BDNF increase and memory persistence.

Previously we showed that activation of the Nucleus of the Solitary Tract (NTS)-Nucleus Paragigantocellularis (PGi)-Locus coeruleus (LC) pathway, which theoretically culminates with norepinephrine (NE) release in dorsal hippocampus (CA1 region) and basolateral amygdala (BLA) is necessary for the consolidation of object recognition (OR) memory. Here we show that, while the microinjection of the beta-noradrenergic receptor blocker timolol into CA1 impairs OR memory consolidation, the microinjection of norepinephrine (NE) promotes the persistence of this type of memory. Further, we show that OR consolidation is attended by an increase of norepinephrine (NE) levels and of the expression of brain derived neurotrophic factor (BDNF) in hippocampus, which are impaired by inactivation of the NTS-PGi-LC pathway by the infusion of muscimol into the NTS.

One-single physical exercise session after object recognition learning promotes memory persistence through hippocampal noradrenergic mechanisms

&NA; Previously we showed the involvement of the hippocampal noradrenergic system in the consolidation and persistence of object recognition (OR) memory. Here we show that one‐single physical exercise session performed immediately after learning promotes OR memory persistence and increases norepinephrine levels in the hippocampus. Additionally, effects of exercise on memory are avoided by an intra‐hippocampal beta‐adrenergic antagonist infusion. Taken together, these results suggest that exercise effects on memory can be related to noradrenergic mechanisms and acute physical exercise can be a non‐pharmacological intervention to assist memory consolidation and persistence, with few or no side effects. HighlightsAcute physical exercise promotes recognition memory persistence.Physical exercise effects on memory are similar to norepinephrine effects.Acute physical exercise increases norepinephrine levels in hippocampus.

Paraquat exposure-induced Parkinson’s disease-like symptoms and oxidative stress in Drosophila melanogaster: Neuroprotective effect of Bougainvillea glabra Choisy

Extracts from the leaves of Bougainvillea glabra Choisy are used in traditional medicines, but their actions on the central nervous system have not been studied. In the present study, we investigated the potential neuroprotective effects of Bougainvillea glabra Choisy leaf extract (BG extract) against paraquat (PQ)-induced neurotoxicity. Male adult wild-type flies (1- 4days old) were exposed to PQ (3.5mM) and/or BG extract (120μg/mL) through food for 4days. PQ-fed flies had decreased locomotor capacity in negative geotaxis and crossing number assays and had a higher incidence of mortality than the control group. PQ neurotoxicity was also associated with a marked decrease in dopamine levels and increase in acetylcholinesterase (AChE) activity, reactive oxygen species (ROS) production and lipid peroxidation. Co-exposure to BG extract prevented mortality, and dopamine depletion, improved locomotor performance and decreased AChE activity, ROS production and lipid peroxidation. GC-MS and HPLC analyses of BG extract revealed the presence of many antioxidant compounds such as phytol, α,γ-tocopherol, squalene, stigmasterol, geranylgeraniol, quercetin, and caffeic, vanillic, coumaric, ferulic acids. Our results showed neuroprotective effects of BG extract, reflecting the presence of antioxidant compounds. Thus, we suggested that B. glabra leaves could be considered an effective agent in the prevention of neurological disorders, where dopamine depletion and/or oxidative stress are involved, as in Parkinsons disease (PD).

FITORREMEDIAÇÃO DOS HERBICIDAS 2,4-DICLOROFENOXIACÉTICO E PROPANIL EM SOLO CULTIVADO POR ERVA CIDREIRA (MELISSA OFFICINALIS)

O uso frequente ou incorreto de pesticidas pode acarretar em contaminacoes no solo, aguas e alimentos. Para evitar tais contaminacoes o presente estudo avaliou o potencial de fitorremediacao da Melissa officinalis em solo contendo uma mistura dos pesticidas comerciais Aminol e Herbipropanin (2,4-D e propanil). Amostras de solo (250,0 g) foram fortificadas com tres concentracoes da mistura dos pesticidas comerciais (0,1612 g Kg -1 + 0,072 g Kg -1 ; 0,0806 g Kg -1 + 0,0403 g Kg -1 ; 0,036 g Kg -1 + 0,018 g Kg -1 , de Aminol e de Herbipropanin respectivamente) onde foram plantadas as mudas. Coletas sucessivas desse solo (10,0 g) foram realizadas para proceder a extracao destes compostos com solventes orgânicos (metanol/acetato de etila 50:50 v/v) para serem analisadas em cromatografia liquida de alta eficiencia com arranjo de diodos a fim de avaliar se havia diminuicao dos compostos pela utilizacao da planta. Os resultados demonstraram que houve uma diminuicao nos compostos cultivados com a planta durante 20 dias de cultivo. Esse estudo mostrou que o cultivo de Melissa officinalis pode ser uma estrategia rapida, eficaz e de baixo custo para a fitorremediacao de solos contaminados pelos herbicidas 2,4-D e propanil e, ainda, promissora na remediacao do metabolito 3,4-DCA.

The phytoremediation potential of Plectranthus neochilus on 2,4-dichlorophenoxyacetic acid and the role of antioxidant capacity in herbicide tolerance

The possible phytoremediation capacity of Plectranthus neochilus (boldo) exposed to the commercial pesticide (Aminol) in soil and water through consecutive extractions (days interval) was evaluated. After the exposure period, tea leaves from the plant were analyzed in terms of the presence of 2,4-D, total antioxidant capacity (DPPH), concentration of total polyphenols and flavonoids for plants exposed to soil and water. In water, 2,4-D remained up to 67% in the 60 days of experiment in the control group, which provided the use of two treatment groups with the plant (one group of plants for 30 days and another group in the remaining 30 days in the same system), thus, a decontamination up to 49% of the 2,4-D was obtained in this system with water. In both experiments (soil and water) the 2,4-D was not detected in tea leaves, the reduction of the antioxidant activity, polyphenols and flavonoids of plants exposed to the herbicide was also observed when compared to the non-exposed plants. In tea - plants in water - it was also possible to quantify the phenolic compounds and it was observed that in the group of plants of the first 30 days there was a decrease in caffeic acid and an increase in coumaric and ferulic acids, compared to the group of plants that were not exposed to 2,4-D. In the remaining 30 days with the new seedlings there was a decrease of the coumaric acid and an increase of the caffeic and ferulic acids.