Both prolactin (PRL) and a molecular mimic of phosphorylated PRL, S179D-PRL, protect the hippocampus of female rats against excitotoxicity

Morales, Teresa; Lorenson, Mary Y.; Walker, Ameae M.; Ramos, Eugénia

doi:10.1016/j.neuroscience.2013.11.015

Cited by 36 publications

(22 citation statements)

References 47 publications

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“…Molecular pathways that contribute to the protection against Glu‐induced excitotoxicity in the rat brain are of great interest. The neuroprotective effects of prolactin (PRL) and estrogen as female sex hormones against hippocampal neurodegeneration have been extensively studied (Velíšková, Velisek, Galanopoulou, & Sperber, ; Ciriza, Azcoitia, & García‐Segura, ; Tejadilla, Cerbón, & Morales, ; Morales, Lorenson, Walker, & Ramos, ). Previous work has shown that pretreatment with PRL diminishes hippocampal neurodegeneration caused by the Glu agonist kainic acid (Tejadilla et al, ; Morales et al, ) in ovariectomized females.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the glutamate signaling pathway in juvenile rats

Al-Suwailem

Abdi

El‐Ansary

2017

J of Neuroscience Research

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Females have been found to be at lower risk for the development of neurodevelopmental disorders than males. The greater neuroprotection in females is mostly due to female sex hormones. Estrogen is hypothesized to provide neuroprotection by suppressing the neuro-excitotoxicity induced by glutamate (Glu). This study was conducted to understand the effect of sex in modulating Glu signaling in juvenile rats. Brain tissue homogenate of 15 Wistar albino rats (9 males, 6 females) weighing 60 to 80 g and aged approximately 28 days was used. Biochemical parameters related to Glu signaling, such as the absolute and relative concentrations of Glu, gamma aminobutyric acid (GABA), and glutamine, as well as glutamate transporter 1 (GLT1), glutamine synthetase (GS), glutaminase (GLN), and glutamate decarboxylase-67 (GAD-67), were measured by ELISA. The data obtained demonstrated that compared with the levels in males, female rats exhibited significantly lower levels of Glu (p = .001) and GLN/GS (p = .021). The Glu/GABA and Glu/GLT1 ratios as well as the levels of GAD-67 were also lower in female rats, although the difference was not significant. The GLN/GAD-67 ratio (p = .027) and levels of GS (p = .019) were significantly higher in female rats than in males. Multiple regression analysis confirmed the role of GLN/GS, together with the much higher affinity of GLT1 to Glu, in avoiding excitotoxicity in females. In conclusion, there was a significant difference in Glu signaling between female and male rats. The females exhibited a lower susceptibility to develop Glu-induced excitotoxicity, an etiological mechanism for multiple neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 99%

Sex differences in the glutamate signaling pathway in juvenile rats

Al-Suwailem

Abdi

El‐Ansary

2017

J of Neuroscience Research

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“…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.…”

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

confidence: 72%

“…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%

“…Based on reports by Mak and Weiss on parental recognition, reports on the role of PRL in paternal behaviour and work from our laboratory exploring the neuroprotective effects of PRL in female and male (Anagnostou I, Muñoz D, & Morales T, unpublished data) rodents, we hypothesised that PRL would play a role in the neuroprotective effects of paternity in our experiments. Interestingly, western blots of hippocampus showed that monomeric PRL was down‐regulated in sires in the first week postpartum and remained lower than in the corresponding control groups after KA treatment.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Other reports show that an increase in BBB permeability is directly related to the presence of seizures in both, animals and humans (Oby and Janigro, 2006;Marchi et al, 2007;van Vliet et al, 2007). In this context, recent reports indicate that PRL is able to attenuate the kainic acid-induced seizure behavior in the rat, but the mechanisms involved are not fully understood (Tejadilla et al, 2010;Morales et al, 2014). The present data could provide one possible explanation of where PRL may strengthen the BBB and because of that, it could be possible that the kainic acid-induced seizure behavior decreases (Tejadilla et al, 2010).…”

Section: Discussionmentioning

confidence: 99%