Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

Rivero-Segura, Nadia Alejandra; Flores‐Soto, Edgar; Cadena, Selene García de la; Coronado-Mares, Isabel; Gómez-Verján, Juan Carlos; Ferreira, Diana G.; Cabrera-Reyes, Erika Alejandra; Lopes, Luı́sa V.; Massieu, Lourdes; Cerbón, Marco

doi:10.1371/journal.pone.0176910

Cited by 54 publications

(32 citation statements)

References 56 publications

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“…More specifically, the dam presents a significant local up‐regulation of antiapoptotic protein Bcl‐2 levels compared to dioestrus virgin rats under basal conditions, and lower cell death (FJC) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling), no significant loss of neurones (NeuN), lower astrogliosis, and reduced microglial response (GFAP and Iba1 fluorescence levels and Scholl morphometric analysis of individual astrocytes) after both peripheral and central administration of KA . Some of these effects are attributed to PRL, which is highly expressed during lactation and has been shown to have protective effects in both in vivo and in vitro experiments …”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, we demonstrate for the first time that parental in- 13,14 Some of these effects are attributed to PRL, which is highly expressed during lactation and has been shown to have protective effects in both in vivo [23][24][25] and in vitro experiments. 26,27 Hormones of reproduction, in particular PRL, have been considered to play a significant role in the expression of paternal behaviour in mammals; for example, various species show higher circulating levels of PRL after birth or contact with their offspring. 28 .…”

Section: Interaction With the Pups And Dam But Not The Pregnant Femmentioning

confidence: 99%

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Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

Anagnostou¹,

Morales²

2019

J Neuroendocrinology

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Parental experience imposes neuroplasticity in the hippocampus of females and males. In lactating rat dams, the hippocampus is protected against excitotoxic damage by kainic acid lesioning, although it is still unknown whether paternity can provide such protection to male rodents. To evaluate the protective effects of fatherhood against excitotoxic lesions, we paired male mice with females and co‐housed them until the day of parturition (PPD0), when we randomly assigned them to two groups: (i) the pregnancy group (males housed individually overnight and injected i.c.v. with 100 ng per 1 μL of kainic acid or vehicle on PPD1) and (ii) the sire group (males housed with the dam and pups until PPD8, when injected i.c.v. after evaluation of parental behaviour). Individually housed virgin adult male mice formed the control group. Markers of neurodegeneration (NeuN, Fluoro‐Jade C) and astrogliosis (glial fibrillary acidic protein) were evaluated in fixed cerebral tissue containing the dorsal CA1, CA3 and CA4 hippocampal subfields. The CA1 subfield did not suffer damage in any of the experimental groups. The sire group exhibited less neurodegeneration and astrogliosis in the CA3 and CA4 subfields compared to their respective controls, independently of the expression of parental behaviour. Western blot analysis was conducted for prolactin (PRL), PRL receptor and related intracellular pathways. Monomeric PRL was lower in the hippocampus of sires in the first week postpartum with a parallel rise of a 48‐kDa dimerised isoform compared to virgin controls. The long isoform of PRL receptor did not change, and signal transducer and activator of transcription 5 (STAT5) was not detected in the hippocampus. However, a sustained rise in pAkt, a signalling molecule that participates in cell survival, was observed in the sire group. These results indicate that the hippocampus of sires housed with the dam and pups is less sensitive to neurotoxic injury, which might not be primarily regulated by PRL‐STAT5‐modulated mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Interaction With the Pups And Dam But Not The Pregnant Femmentioning

confidence: 99%

Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

Anagnostou¹,

Morales²

2019

J Neuroendocrinology

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“…Hyperpolarisations in SFO neurones following PRL application may be the result of an increase in the activity of Ca 2+ ‐dependent K + channels, as is observed in Chinese hamster ovary cells following 4 nmol L ‐1 PRL application . Furthermore, experiments on cultured hippocampal neurones showed that PRL application increased intracellular Ca 2+ levels; this may also lead to an increase in Ca 2+ ‐dependent K + channel activation. An additional channel contributing to depolarisations in SFO neurones may be TRP as functional TRP channels are found in the SFO and PRL has been shown to increase TRP channel activation .…”

Section: Discussionmentioning

confidence: 99%

The subfornical organ: A novel site for prolactin action

Kamesh

Black

Ferguson

2018

J Neuroendocrinology

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Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL-R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood-brain barrier. Accordingly, areas of the brain that do not possess a blood-brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL-R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real-time polymerase chain reaction, we found that PRL-R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch-clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 μmol L PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, -6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L to 1 μmol L , the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K current in 67% of SFO neurones in voltage-clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL-R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.

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“…We performed the immunocytochemistry for all treatments according to the methodology of [42]. Briefly, K562 cells were cultured in round, glass coverslips and treated with MABB for 18 h and incubated with polyclonal antibodies of anti-Bax (1 : 100), anti-Bak (1 : 100), and anti-Bcl-2 (1 : 100) (Santa Cruz Biotechnology) overnight at 4°C.…”

Section: Immunofluorescence Of Bak Bcl-2 and Baxmentioning

confidence: 99%

Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense

et al. 2018

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Mammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree , which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as a mixture) possess biological properties such as cytotoxic and antitumoral activities, however, most of its molecular targets remain unknown. In this context, novel bioinformatic approaches, such as network pharmacology analysis, have been successfully used in herbal medicine to accelerate research in this field, and the support of experimental validations has been shown to be quite robust. In the present study, we performed a network pharmacology analysis to assess the possible molecular biological networks that interact with mammea A/BA and A/BB. Moreover, we validated the most relevant networks experimentally on K562 cancer cells. The results of the network pharmacology analysis indicate that mammea A/BA and A/BB interacts with cell death, PI3K/AKT, MAPK, Ras, and cancer pathways. The model shows that mammea A/BA and A/BB induce apoptosis through the overexpression of the proapoptotic proteins Bax and Bak, disrupt the autophagic flux as seen by the cytosolic accumulation of LC3-II and p62, disrupting the mitochondria ultrastructure and concomitantly increase the intracellular calcium concentration. Additionally, docking analysis predicted a possible interaction with a rapamycin-binding domain of mTOR. In conclusion, we validated network pharmacology analysis and report, for the first time, that mammea A/BA and A/BB coumarins induce apoptosis through the inhibition of the autophagic flux, possibly interacting with mTOR.

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Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

Cited by 54 publications

References 56 publications

Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

The subfornical organ: A novel site for prolactin action

Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense

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