scholarly journals Rapid and Widespread Effects of 17β-Estradiol on Intracellular Signaling in the Male Songbird Brain: A Seasonal Comparison

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1364-1376 ◽  
Author(s):  
Sarah A. Heimovics ◽  
Nora H. Prior ◽  
Chris J. Maddison ◽  
Kiran K. Soma

Across vertebrate species, 17β-estradiol (E2) acts on the brain via both genomic and nongenomic mechanisms to influence neuronal physiology and behavior. Nongenomic E2 signaling is typically initiated by membrane-associated estrogen receptors that modulate intracellular signaling cascades, including rapid phosphorylation of ERK. Phosphorylated ERK (pERK) can, in turn, rapidly phosphorylate tyrosine hydroxylase (TH) and cAMP response element-binding protein (CREB). Recent data suggest that the rapid effects of E2 on mouse aggressive behavior are more prominent during short photoperiods (winter) and that acute aromatase inhibition reduces songbird aggression in winter only. To date, seasonal plasticity in the rapid effects of E2 on intracellular signaling has not been investigated. Here, we compared the effects of acute (15 min) E2 treatment on pERK, pTH, and pCREB immunoreactivity in male song sparrows (Melospiza melodia) pretreated with the aromatase inhibitor fadrozole during the breeding and nonbreeding seasons. We examined immunoreactivity in 14 brain regions including portions of the song control system, social behavior network, and the hippocampus (Hp). In both seasons, E2 significantly decreased pERK in nucleus taeniae of the amygdala, pTH in ventromedial hypothalamus, and pCREB in mesencephalic central gray, robust nucleus of the arcopallium, and caudomedial nidopallium. However, several effects were critically dependent upon season. E2 decreased pERK in caudomedial nidopallium in the breeding season only and decreased pCREB in the medial preoptic nucleus in the nonbreeding season only. Remarkably, E2 decreased pERK in Hp in the breeding season but increased pERK in Hp in the nonbreeding season. Together, these data demonstrate that E2 has rapid effects on intracellular signaling in multiple regions of the male brain and also demonstrate that rapid effects of E2 can be profoundly different across the seasons.

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3055-3061 ◽  
Author(s):  
István M. Ábrahám ◽  
Martin G. Todman ◽  
Kenneth S. Korach ◽  
Allan E. Herbison

Abstract Estrogen exerts classical genomic as well as rapid nongenomic actions on neurons. The mechanisms involved in rapid estrogen signaling are poorly defined, and the roles of the classical estrogen receptors (ERs α and β) are unclear. We examined here the in vivo role of classical ERs in rapid estrogen actions by evaluating the estrogen-induced effects on two major signaling pathways within the brains of αER-, βER-, and double αβER-knockout (ERKO) ovariectomized female mice. Estrogen significantly (P < 0.05) increased the numbers of phospho-cAMP response element binding protein (phospho-CREB)-immunoreactive cells in specific brain regions of wild-type mice in a time-dependent manner beginning within 15 min. In brain areas that express predominantly ERβ, this response was absent in βERKO mice, whereas brain regions that express mostly ERα displayed no change in αERKO mice. In the medial preoptic nucleus (MPN), an area that expresses both ERs, the estrogen-induced phosphorylation of CREB was normal in both αERKO and βERKO mice. However, estrogen had no effect on CREB phosphorylation in the MPN, or any other brain region, in double αβERKO animals. Estrogen was also found to increase MAPK phosphorylation levels in a rapid (<15 min) manner within the MPN. In contrast to CREB signaling, this effect was lost in either αERKO or βERKO mice. These data show that ERα and ERβ play region- and pathway-specific roles in rapid estrogen actions throughout the brain. They further indicate an indispensable role for classical ERs in rapid estrogen actions in vivo and highlight the importance of ERs in coordinating both classical and rapid actions of estrogen.


2021 ◽  
Vol 14 ◽  
Author(s):  
Carlos Sánchez-Huertas ◽  
Eloísa Herrera

During the establishment of neural circuitry axons often need to cover long distances to reach remote targets. The stereotyped navigation of these axons defines the connectivity between brain regions and cellular subtypes. This chemotrophic guidance process mostly relies on the spatio-temporal expression patterns of extracellular proteins and the selective expression of their receptors in projection neurons. Axon guidance is stimulated by guidance proteins and implemented by neuronal traction forces at the growth cones, which engage local cytoskeleton regulators and cell adhesion proteins. Different layers of guidance signaling regulation, such as the cleavage and processing of receptors, the expression of co-receptors and a wide variety of intracellular cascades downstream of receptors activation, have been progressively unveiled. Also, in the last decades, the regulation of microtubule (MT) assembly, stability and interactions with the submembranous actin network in the growth cone have emerged as crucial effector mechanisms in axon pathfinding. In this review, we will delve into the intracellular signaling cascades downstream of guidance receptors that converge on the MT cytoskeleton of the growing axon. In particular, we will focus on the microtubule-associated proteins (MAPs) network responsible of MT dynamics in the axon and growth cone. Complementarily, we will discuss new evidences that connect defects in MT scaffold proteins, MAPs or MT-based motors and axon misrouting during brain development.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xueyan Fu ◽  
Will Patterson ◽  
Gregory Dolnikowski ◽  
Bess Dawson-Hughes ◽  
Martha Morris ◽  
...  

Abstract Objectives Very little is known about the forms of vitamin D and vitamin K in the human brain. The objective of this study is to evaluate concentrations of vitamin D and vitamin K forms in human brain and their correlations across four human brain regions. Methods Vitamin D [D3, 25(OH)D and 1,25(OH)2D] and vitamin K [phylloquinone and menaquinone-4 (MK4)] concentrations were measured by LC/MS/MS and HPLC, respectively, in four brain regions from post-mortem samples obtained from participants in the Rush Memory and Aging Project (n = 130, mean age 82 yrs, 81% female). The brain regions analyzed were the mid-frontal cortex (MF) and mid-temporal cortex (MT) [two regions important for memory in Alzheimer's Disease (AD)], the cerebellum (CR, a region not affected by AD), and the anterior watershed white matter (AWS, a region associated with vascular disease). The correlations among the vitamin forms across brain regions were calculated using Spearman rank order correlation coefficients. Significance was set at P < 0.001. Results The average concentrations of vitamin D3, 25(OH)D and MK4 were 604 pg/g, 535 pg/g, and 3.4 pmol/g, respectively. 25(OH)D and MK4 were detected in >95% of the brain samples. Nearly 92% of 1,25(OH)2D and 80% of phylloquinone samples had concentrations below the limit of assay detection (LOD) 1,25(OH)2D = 20 ng/g, phylloquinone = 0.1 pmol/g). Vitamin D3 and 25(OH)D concentrations were positively correlated across all four regions (all Spearman r ≥ 0.78, P < 0.0001). The 1,25(OH)2D was significantly correlated between the MF and CR regions only (Spearman r = 0.30, P < 0.001, all other P ≥ 0.002). MK4 and PK were positively correlated across the four regions studied (MK4 all Spearman r ≥ 0.78, phylloquinone r ≥ 0.49, all P < 0.001). Conclusions To the best of our knowledge, this study is the first evaluation of the concentrations of vitamin D and vitamin K forms in multiple regions of the human brain. Overall, the vitamin D and vitamin K forms were each positively correlated across the four brain regions studied. Future studies are needed to clarify the roles of these nutrients in AD and dementia. Funding Sources National Institute of Aging.


2019 ◽  
Vol 21 (1) ◽  
pp. 181 ◽  
Author(s):  
Maheedhar Kodali ◽  
Olagide W. Castro ◽  
Dong-Ki Kim ◽  
Alicia Thomas ◽  
Bing Shuai ◽  
...  

Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stem cells (hMSCs) have great promise as biologics to treat neurological and neurodegenerative conditions due to their robust antiinflammatory and neuroprotective properties. Besides, intranasal (IN) administration of EVs has caught much attention because the procedure is noninvasive, amenable for repetitive dispensation, and leads to a quick penetration of EVs into multiple regions of the forebrain. Nonetheless, it is unknown whether brain injury-induced signals are essential for the entry of IN-administered EVs into different brain regions. Therefore, in this study, we investigated the distribution of IN-administered hMSC-derived EVs into neurons and microglia in the intact and status epilepticus (SE) injured rat forebrain. Ten billion EVs labeled with PKH26 were dispensed unilaterally into the left nostril of naïve rats, and rats that experienced two hours of kainate-induced SE. Six hours later, PKH26 + EVs were quantified from multiple forebrain regions using serial brain sections processed for different neural cell markers and confocal microscopy. Remarkably, EVs were seen bilaterally in virtually all regions of intact and SE-injured forebrain. The percentage of neurons incorporating EVs were comparable for most forebrain regions. However, in animals that underwent SE, a higher percentage of neurons incorporated EVs in the hippocampal CA1 subfield and the entorhinal cortex, the regions that typically display neurodegeneration after SE. In contrast, the incorporation of EVs by microglia was highly comparable in every region of the forebrain measured. Thus, unilateral IN administration of EVs is efficient for delivering EVs bilaterally into neurons and microglia in multiple regions in the intact or injured forebrain. Furthermore, incorporation of EVs by neurons is higher in areas of brain injury, implying that injury-related signals likely play a role in targeting of EVs into neurons, which may be beneficial for EV therapy in various neurodegenerative conditions including traumatic brain injury, stroke, multiple sclerosis, and Alzheimer’s disease.


1990 ◽  
Vol 104 (3) ◽  
pp. 477-488 ◽  
Author(s):  
Ann C. Hennessey ◽  
Lael Camak ◽  
Frank Gordon ◽  
David A. Edwards

Behaviour ◽  
1974 ◽  
Vol 49 (1-2) ◽  
pp. 152-195 ◽  
Author(s):  
Jeannette P. Hanby ◽  
Conrad E. Brown

AbstractSociosexual behaviours were observed over a two-year period in a natural troop of about 100 Japanese macaques (Macaca fuscata) confined in a two-acre corral. The development and mature expression of integrated patterns of mounting, presenting, thrusting, and related behaviours were examined. The frequency and type of mounting varied dramatically with the season of the year. Male-female, female-male, and female-female mounting were most frequent during the 6-month breeding season when males 4½ years and older can ejaculate and females 3½ years and older can conceive. Ejaculation generally occurred only after a series of mounts. Mountings in series by and on either sex were largely confined to the breeding season. Female presenting and male thrusting and certain other behaviours accompanied mounting more often at that time of year also. In the nonbreeding season, heterosexual interactions decreased but male-male mounting increased though it never reached breeding season levels for male-female mounting. Nonbreeding season mount events between both sexes and all ages typically involved only a single mount, but most were accompanied by thrusts. The type of interaction between pair members also differed; most mounting occurred during play. In males, mounting and thrusting were integrated gradually according to the season and sex of partner. By six months of age, males oriented to a partner's buttocks and used a double-foot-clasp posture on most mounts. At 1½ males mounted females more frequently than males and by 2½ showed the seasonal cycles in mount frequency and partner choice. They reached peaks in mount event frequency at 4½, but the most efficient and stable patterns were seen in males over 7 years of age. Although females showed thrusting movements early in life, they seldom mounted except on males during breeding season and occasionally during play or agonistic situations. They were most active as mount partners and actors after 3½ years of age. Their subsequent activity varied with the individual and her reproductive state. Several conclusions can be drawn from this and other studies on the development of sociosexual behaviours in primates. 1. Rearing conditions are crucial to the development and integration of postures, thrusting, intromission, and ejaculation. The most important element for normal development is the mother; however, the presence of other adult and encouraging females helps a young male to integrate the various elements. Peer males and females also facilitate or allow the expression of a variety of patterns and probably provide a source of enduring attachments and mature partner preferences. The role of the adult males in development is both positive and negative depending on the male, the group, and the species. 2. The most important aspect of normal sociosexual development is the differentiation and integration of elements such as mounting, presenting, thrusting, intromission into two patterns : the primarily copulatory and the primarily contacting. Intromission seems to be a key element in the differentiation process. Factors that facilitate intromission speed the process; factors that inhibit intromission delay the development of the young primate male's ability to distinguish correctly between postures, partners, and situations. The copulatory patterns of females seem less affected by unsatisfactory rearing conditions, but the sociosexual patterns of contact may be disturbed. 3. Mature sociosexual patterns develop from close physical contact with the mother or mother substitutes. Erection and thrusting appear independently but soon become linked to ventral clinging, embracing, riding, and mounting. Mount and present postures develop quickly and vary according to species and pairings and contexts. The most stereotyped posturing and patterns appear in the copulatory context: the sociosexual patterns retain their variability in form and variety of expression in different contexts, mainly affiliative and more rarely, agonistic,


2015 ◽  
Vol 59 (3) ◽  
Author(s):  
H. Zhang ◽  
Y. Wang ◽  
J. Zhang ◽  
L. Wang ◽  
Q. Li ◽  
...  

The nerve growth factor (NGF) not only has an essential effect on the nervous system, but also plays an important role in a variety of non-neuronal systems, such as the reproductive system. The aim of this study was to investigate the seasonal changes in<strong> </strong>expression of NGF and its receptors (TrkA and p75) in testes of the wild ground squirrel during the breeding and nonbreeding seasons.<strong> </strong>Immunolocalization for NGF was detected mainly in Leydig cells and Sertoli cells in testes of the breeding and nonbreeding seasons. The immunoreactivity of TrkA was highest in the elongated spermatids, whereas p75 in spermatogonia and spermatocytes in testes of the breeding season. In the nonbreeding season testes, TrkA showed positive immunostainings in Leydig cells, spermatogonia and primary spermatocytes, while p75 showed positive signals in spermatogonia and primary spermatocytes. Consistent with the immunohistochemical results, the mean mRNA and protein level of NGF and TrkA were higher in the testes of the breeding season, and then decreased to a relatively low level in the nonbreeding season. In addition, the concentration of plasma gonadotropins and testosterone were assayed by radioimmunoassay (RIA), and the results showed a significant seasonal change between the breeding and nonbreeding seasons. To conclude, these results of this study provide the first evidence on the potential involvement of NGF and its receptor, TrkA and p75 in the seasonal spermatogenesis and testicular function change of the wild ground squirrel.


2010 ◽  
Vol 22 (1) ◽  
pp. 360
Author(s):  
M. I. Cueto ◽  
F. Pereyra-Bonnet ◽  
P. Silvestre ◽  
A. E. Gibbons

The aim of the study was to assess possible variations in superovulatory yields due to different FSH treatments at 2 times of the year. Superovulation and embryo recovery were performed during the breeding (n = 63) andnonbreeding (n = 46) seasons in Merino ewes located at 41°S latitude. Animals were kept under the same conditions, housed outdoors in a sheltered and covered pen, and were fed a liveweight maintenance ration. All animals received 60-mg medroxyprogesterone acetate intravaginal sponges (Progespon®, Syntex, Buenos Aires, Argentina) for 14 days. Ewes were then randomly assigned to 2 different superovulatory treatments: classic (n = 74) and one shot (n = 35) in both seasons. Classic superovulatory treatment consisted of 7 decreasing doses (2 × 48 mg, 2 × 24 mg, 2 × 20 mg, and1 × 16 mg NIH-FSH-P1)ofFSH (Folltropin®-V, Bioniche, Belleville, Ontario, Canada), administered twice daily from 48 h before to 24 h after pessary removal. A dose of eCG (300 IU; Novormon®, Syntex) was administered at progestagen removal. One shot superovulatory treatment consisted of a single dose of FSH (70 mg NIH-FSH-P1) plus 300 UI of eCG injected at pessary withdrawal. Embryo donors were inseminated by laparoscopy with frozen-thawed semen (100 × 106 spz) 12 h after the onset of estrus. Surgical embryo recovery was done on Day 7 after sponge withdrawal and embryos were graded for quality according to morphology (Grade 1 = excellent or good; Grade 2 = fair; Grade 3 = poor; and Grade 4 = dead or degenerated; IETS 1998). A 2 × 2 factorial ANOVA was used to test the main effects (season and superovulatory treatment) and interactions. There were no significant differences in the proportion of responding ewes (>3 corpora lutea), ovulation rate, and recovered Grades 1 to 2 embryos between the breeding and nonbreeding season (Table 1; P > 0.05). However, number of recovered ova/embryos and ova/embryo recovery rate were higher during the breeding season compared with the nonbreeding season, whereas the percentage of nonfertilized ova was lower in the breeding season than in the nonbreeding season (P < 0.05). Analysis of data comparing superovulatory treatments showed that the proportion of responding ewes, ovulation rate, recovered embryos, and recovered Grades 1 to 2 embryos were lower for the one shot treatment than for the classic treatment (P < 0.05). Embryo recovery rate and nonfertilization rate did not differ between treatments (P > 0.05). It was concluded that there was an increase in the number of total recovered ova/embryos during the breeding season compared with the nonbreeding season, although the number of recovered good-quality embryos was not affected. The use of multiple FSH injections produced a higher number of total recovered and viable embryos in Merino sheep than the one shot superovulatory treatment. Table 1.Embryo yields in ewes submitted to superovulation


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