Previous studies indicated that there is a separate hypothalamic control of follicle-stimulating ... more Previous studies indicated that there is a separate hypothalamic control of follicle-stimulating hormone (FSH) release distinct from that of luteinizing hormone (LH). An FSH-releasing factor (FSHRF) was purified from rat and sheep hypothalami, but has not been isolated. We hypothesized that FSHRF might be an analogue of mammalian luteinizing hormone-releasing hormone (m-LHRH) and evaluated the activity of many analogues of m-LHRH and of the known LHRHs found in lower forms. Here we demonstrate that lamprey (l) LHRH-III has a potent, dose-related FSH-but not LH-releasing action on incubated hemipituitaries of male rats. l-LHRH-I on the other hand, had little activity to release either FSH or LH. m-LHRH was equipotent to l-LHRH-III to release FSH, but also had a high potency to release LH in contrast to l-LHRH-III that selectively released FSH. Chicken LHRH-II had considerable potency to release both LH and FSH, but no selectivity in its action. Salmon LHRH had much less potency than the others tested, except for l-LHRH-I, and no selectivity in its action. Because ovariectomized, estrogen, progesterone-treated rats are a sensitive in vivo assay for FSHand LH-releasing activity, we evaluated l-LHRH-III in this assay and found that it had a completely selective stimulatory effect on FSH release at the two doses tested (10 and 100 pmols). Therefore, l-LHRH-III is a highly potent and specific FSH-releasing peptide that may enhance fertility in animals and humans. It may be the long sought after m-FSHRF.
Docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acid (n-3PUFA) in the bra... more Docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acid (n-3PUFA) in the brain, has attracted great importance for a variety of neuronal functions such as signal transduction through plasma membranes, neuronal plasticity, and neuroprotection. Astrocytes that provide structural, functional, and metabolic support for neurons, express ∆6- desaturase encoded by FADS2 gene that can be, next to the plasma DHA pool, additional source of DHA in the brain. Furthermore, the genetic variations of FADS gene cluster has been found in children with developmental disorders, and are associated with cognitive functions. Since, the regulation of DHA biosynthesis in astrocytes remains poorly studied the aim of this study was to determine the effect of palmitic acid (PA), α-linolenic acid (ALA) or docosahexaenoic acid (DHA), on the transcription of FADS2 gene in astrocytes and survival of neurons challenged with oxidative compounds after co-culture with astrocytes exposed to DHA. The lipid profile in cell membranes after incubation with fatty acids was determined by gas chromatography, and FADS2 expression was analyzed using real-time PCR. The viability of neurons cocultured with PUFA-enriched astrocytes was investigated by flow cytometry after staining cells with annexin V-FITC and PI. The results showed that DHA suppressed (P <0.01), PA stimulated (P <0.01), while ALA did not change the FADS2 gene expression after 24 h incubation of astrocytes with fatty acids. Although FADS2 mRNA was down-regulated by DHA, its level in astrocytic membranes significantly increased (P <0.01). Astrocytes with DHA-enriched membrane phospholipids markedly enhanced neuronal resistance to cytotoxic compounds and neuronal survival. These results suggest that beneficial effects of supplementation with n-3 PUFA in Alzheimer disease and in psychiatric disorders is caused, in part, by increased efficacy of DHA-enriched astrocytes to protect neurons under adverse conditions in the brain.
The effect of substance P (SP) on gonadotropin releasing hormone (GnRH) content in the medial bas... more The effect of substance P (SP) on gonadotropin releasing hormone (GnRH) content in the medial basal hypothalamus (MBH) was studied. To evaluate this effect, 5 microg of SP in saline or saline alone were injected into the 3rd cerebral ventricle in conscious ovariectomized (OVX) and ovariectomized with subcutaneously implanted 17beta-estradiol capsules (OVX+E[_2]) rats. Two hours later the animals were decapitated and GnRH was estimated by radioimmunoassay in the tissue extracts from MBH. SP injected i.c.v. had no effect on the GnRH content in MBH in OVX rats. However, SP significantly decreased GnRH content in OVX+E[_2] rats. These results provide evidence that SP participates in the control of GnRH neurons within MBH. It is suggested that SP may stimulate GnRH release from GnRH neuron terminals and that estrogen may be involved in this process.
The aim of our work was to examine the cytotoxicity of NiCr alloys coated with Ti(C,N) with diffe... more The aim of our work was to examine the cytotoxicity of NiCr alloys coated with Ti(C,N) with different amounts of C and N in the layer on human gingival fibroblasts. Cells were cultured for 24 hours in the alloy extracts or on the surface of tested materials. The viability of the cells exposed to 1-, 3-, 5- and 7-day extracts did not change in comparison to the viability of cells cultured in a control medium assayed by an MTT test. Moreover, the flow cytometry analysis of fibroblasts cultured in direct contact with tested alloys revealed that all coatings except TiC did not induce apoptosis or necrosis. Interestingly, 24 hour fibroblast culture on alloys with Ti(C,N) coatings showed that the number of fibroblasts adhered to these alloys, evaluated by scanning electron microscope, increased with an increase in the content of nitrogen in the layer. The present study demonstrates that Ti(C,N) coatings were not cytotoxic and did not induce apoptosis in Ti(C,N) extracts, nor in direct contact with gingival fibroblasts, and can be considered for biomedical applications in the future.
Proceedings of the Society for Experimental Biology and Medicine, Jul 1, 2000
In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the ea... more In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we determined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h. To determine if this rhythm is controlled by nocturnally released hormones, we evaluated the effect of hormones known to be released at night in humans, some of which are also known to be released at night in rats. In humans, prolactin (PRL), growth hormone (GH), and melatonin are known to be released at night, and adrenocorticotropic hormone (ACTH) release is inhibited. In these experiments, conscious rats were injected intravenously with 0.5 ml diluent or the substance to be evaluated just after removal of the first blood sample (0.3 ml), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 microg) produced a rapid increase in plasma leptin that persisted for the duration of the experiment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, alpha bromoergocryptine (1.5 mg), a dopamine-2-receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the decline persisted for 120 min. The minimal effective dose of GH to lower plasma leptin was 1 mg/rat. Insulin-like growth factor (IGF-1) (10 microg), but not IGF-2 (10 microg), also significantly decreased plasma leptin. Melatonin, known to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter leptin release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0. 1-mg dose but produced a delayed, significant increase in leptin, manifest 100-120 min after injection of a 1 mg dose. Since glucocorticoids decrease at night in humans at the time of the maximum plasma concentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of corticosterone following stress in the rat and that glucocorticoids are not responsible for the circadian rhythm of leptin concentration. Therefore, we conclude that an increase in PRL secretion during the night may be responsible, at least in part, for the nocturnal elevation of leptin concentrations observed in rats and humans.
Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasi... more Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and seems to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin, and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA, and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha, (alpha 1) receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor (TNF) alpha. In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP, which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
Proceedings of the National Academy of Sciences of the United States of America, Feb 4, 1997
1028), the authors request that the following be noted. In the ''Materials and Methods'' section ... more 1028), the authors request that the following be noted. In the ''Materials and Methods'' section on page 1024, paragraph 3, line 9, the authors indicate that they used recombinant human leptin. In fact, they used recombinant murine leptin.
Postȩpy higieny i medycyny doświadczalnej, Dec 31, 2017
<jats:p>Membrane lipids, due to diverse molecular structures, electric charge and different... more <jats:p>Membrane lipids, due to diverse molecular structures, electric charge and different functional characteristic, have a profound role in multiple cytophysiological processes. A better understanding of the membrane structure and changes of its function in a wide range of diseases gave rise to a new approach termed membrane lipid therapy and directed to modifying the membranes. The strategies directed to membrane involve a direct regulation of membrane lipid composition that causes a change of the transmembrane protein function and modifies the organization of membrane microdomains, or regulation of enzyme activity and gene expression to alter membrane lipid composition. Membrane therapy assumes the use of new molecules specifically designed to modify lipid composition and function of abnormal signaling proteins. Therefore, modifications of the lipid composition and organization of membrane microdomains become pharmacological targets to reverse pathological changes in the profile of enzymatically and non-enzymatically generated lipid derivatives or to modify signaling pathways in the cell. The present monography is an update of the canonical membrane model by Singer-Nicolson and describes the therapeutic targets related to the regulation of the composition and organization of the lipids in the plasma membrane. </jats:p>
Prostaglandins Leukotrienes and Essential Fatty Acids, Sep 1, 2018
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Fosfolipidy neuronów, zwłaszcza kory mózgu, zawierają dużą ilość wielonienasyconego kwasu dokozah... more Fosfolipidy neuronów, zwłaszcza kory mózgu, zawierają dużą ilość wielonienasyconego kwasu dokozaheksaenowego (DHA, C22: 6n-3). Podstawowym źródłem tego kwasu dla komórek nerwowych jest pokarm oraz synteza DHA w wątrobie i astrocytach z niezbędnego kwasu a-linolowego (C18: 3n-3). Największy przyrost DHA w mózgu obserwuje się w okresie życia płodowego i przez pierwsze dwa lata życia dziecka. Odpowiednia ilość DHA w fosfolipidach błonowych determinuje wiele czynności komórek nerwowych i tym można tłumaczyć wyraźną ochronę DHA w mózgu podczas deficytu kwasu a-linolowego w pożywieniu. Fosfolipidy z acylem DHA są w błonach mobilne, a błony plazmatyczne zbudowane z takich fosfolipidów są cieńsze, bardziej przepuszczalne dla jonów i małych cząsteczek oraz mają luźniejszą strukturę. Te wszystkie cechy błon zwiększają ich "dynamikę" w porównaniu z błonami zbudowanymi z innych fosfolipidów. Ponadto tworzą środowisko dla skondensowanych w błonach neuronalnych białek receptorowych, kanałowych i peryferyjnych. Od dostępności DHA dla neuronów zależy ilość fosfatydyloseryny w wewnętrznej warstwie lipidów błonowych, dzięki której zwiększa się przeżywalność neuronów w wyniku translokacji/aktywacji kinaz Akt i Raf-1/MEK. Obecność DHA w fosfolipidach błonowych ułatwia tworzenie się kompleksu białek v-SNARE/t-SNARE niezbędnego w procesie egzocytozy pęcherzyków synaptycznych i rozrastania się błon wypustek neuronalnych, co determinuje ich plastyczność. DHA odgrywa istotną rolę neuroprotekcyjną. Stwierdzono hamowanie syntezy PGE 2 oraz ekspresji COX-1 w astrocytach hodowanych w obecności DHA, a oksygenazowe metabolity DHA, szczególnie neuroprotektyny D, mogą tłumić reakcje zapalne i zapobiegać uszkodzeniom lub apoptozie neuronów. Skutki obecności DHA w błonach komórek nerwowych i powstających z niego metabolitów, a także funkcje zależnej od DHA fosfatydyloseryny mogą wyjaśniać korzystne działanie suplementacji DHA w poprawie czynności mózgu i w chorobach neurodegeneracyjnych.
Proceedings of the 11th International Joint Conference on Biomedical Engineering Systems and Technologies, 2018
In this paper, an automatic method of neuron nucleuses localization in the images, taken with the... more In this paper, an automatic method of neuron nucleuses localization in the images, taken with the fluorescent microscope, is presented. The proposed approach has two phases. During the first phase, a properly trained convolutional neural network acts as a non-linear filter which indicates regions of interest. The network architecture and specific method of its training are original concepts of the authors of this work. In the second phase, analysis of these regions allows to identify points representing positions of the nucleuses. To illustrate the method, images of neurons isolated from neonatal rat cerebral cortex were used. These images were inspected by a domain expert and all the visible nucleuses were manually annotated. This allowed not only to objectively assess the obtained detection results but it enabled the application of machine learning as well.
Background Astrocytes are responsible for a broad range of functions that maintain homeostasis in... more Background Astrocytes are responsible for a broad range of functions that maintain homeostasis in the brain. However, their response to the pro-inflammatory cytokines released by activated microglia in various neurological pathologies may exacerbate neurodegenerative processes. Accumulating evidence suggests that omega-3 docosahexaenoic fatty acid (DHA) has an anti-inflammatory effect in various cell cultures studies and in a variety of neurological disorders. In this study we examined the mechanism involved in the inhibition of the pro-inflammatory response by DHA in astrocytes treated with IL-1β. Methods and results Activation of the transcription factors NF-κB and AP-1 was measured in IL-1β-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-α and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-κB to the nucleus, significantly lowered...
The fads2 gene encoding Δ6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is exp... more The fads2 gene encoding Δ6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is expressed in astrocytes. Dietary fatty acids, which cross the blood-brain barrier, may regulate the transcription of lipogenic enzymes through activation of transcription factors such as peroxisome proliferator-activated receptors (PPARs). The PPARs form the transcription complex with retinoid X receptors (RXRs) that are activated by 9-cis retinoic acid, a metabolite of vitamin A (VA). The study examines whether challenge of astrocytes with VA, prior 24-h treatment with palmitic acid (PA), α-linolenic acid (ALA) or docosahexaenoic acid (DHA) has the effect on the FADS2 expression. RT-qPCR showed that in astrocytes not challenged with VA, PA increased fads2 gene expression and DHA decreased it. However, in VA-primed astrocytes, PA doubled the FADS2 mRNA levels, while DHA increased fads2 gene expression, oppositely to non-primed cells. Furthermore, similar changes were seen in VA-primed astro...
Previous studies indicated that there is a separate hypothalamic control of follicle-stimulating ... more Previous studies indicated that there is a separate hypothalamic control of follicle-stimulating hormone (FSH) release distinct from that of luteinizing hormone (LH). An FSH-releasing factor (FSHRF) was purified from rat and sheep hypothalami, but has not been isolated. We hypothesized that FSHRF might be an analogue of mammalian luteinizing hormone-releasing hormone (m-LHRH) and evaluated the activity of many analogues of m-LHRH and of the known LHRHs found in lower forms. Here we demonstrate that lamprey (l) LHRH-III has a potent, dose-related FSH-but not LH-releasing action on incubated hemipituitaries of male rats. l-LHRH-I on the other hand, had little activity to release either FSH or LH. m-LHRH was equipotent to l-LHRH-III to release FSH, but also had a high potency to release LH in contrast to l-LHRH-III that selectively released FSH. Chicken LHRH-II had considerable potency to release both LH and FSH, but no selectivity in its action. Salmon LHRH had much less potency than the others tested, except for l-LHRH-I, and no selectivity in its action. Because ovariectomized, estrogen, progesterone-treated rats are a sensitive in vivo assay for FSHand LH-releasing activity, we evaluated l-LHRH-III in this assay and found that it had a completely selective stimulatory effect on FSH release at the two doses tested (10 and 100 pmols). Therefore, l-LHRH-III is a highly potent and specific FSH-releasing peptide that may enhance fertility in animals and humans. It may be the long sought after m-FSHRF.
Docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acid (n-3PUFA) in the bra... more Docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acid (n-3PUFA) in the brain, has attracted great importance for a variety of neuronal functions such as signal transduction through plasma membranes, neuronal plasticity, and neuroprotection. Astrocytes that provide structural, functional, and metabolic support for neurons, express ∆6- desaturase encoded by FADS2 gene that can be, next to the plasma DHA pool, additional source of DHA in the brain. Furthermore, the genetic variations of FADS gene cluster has been found in children with developmental disorders, and are associated with cognitive functions. Since, the regulation of DHA biosynthesis in astrocytes remains poorly studied the aim of this study was to determine the effect of palmitic acid (PA), α-linolenic acid (ALA) or docosahexaenoic acid (DHA), on the transcription of FADS2 gene in astrocytes and survival of neurons challenged with oxidative compounds after co-culture with astrocytes exposed to DHA. The lipid profile in cell membranes after incubation with fatty acids was determined by gas chromatography, and FADS2 expression was analyzed using real-time PCR. The viability of neurons cocultured with PUFA-enriched astrocytes was investigated by flow cytometry after staining cells with annexin V-FITC and PI. The results showed that DHA suppressed (P <0.01), PA stimulated (P <0.01), while ALA did not change the FADS2 gene expression after 24 h incubation of astrocytes with fatty acids. Although FADS2 mRNA was down-regulated by DHA, its level in astrocytic membranes significantly increased (P <0.01). Astrocytes with DHA-enriched membrane phospholipids markedly enhanced neuronal resistance to cytotoxic compounds and neuronal survival. These results suggest that beneficial effects of supplementation with n-3 PUFA in Alzheimer disease and in psychiatric disorders is caused, in part, by increased efficacy of DHA-enriched astrocytes to protect neurons under adverse conditions in the brain.
The effect of substance P (SP) on gonadotropin releasing hormone (GnRH) content in the medial bas... more The effect of substance P (SP) on gonadotropin releasing hormone (GnRH) content in the medial basal hypothalamus (MBH) was studied. To evaluate this effect, 5 microg of SP in saline or saline alone were injected into the 3rd cerebral ventricle in conscious ovariectomized (OVX) and ovariectomized with subcutaneously implanted 17beta-estradiol capsules (OVX+E[_2]) rats. Two hours later the animals were decapitated and GnRH was estimated by radioimmunoassay in the tissue extracts from MBH. SP injected i.c.v. had no effect on the GnRH content in MBH in OVX rats. However, SP significantly decreased GnRH content in OVX+E[_2] rats. These results provide evidence that SP participates in the control of GnRH neurons within MBH. It is suggested that SP may stimulate GnRH release from GnRH neuron terminals and that estrogen may be involved in this process.
The aim of our work was to examine the cytotoxicity of NiCr alloys coated with Ti(C,N) with diffe... more The aim of our work was to examine the cytotoxicity of NiCr alloys coated with Ti(C,N) with different amounts of C and N in the layer on human gingival fibroblasts. Cells were cultured for 24 hours in the alloy extracts or on the surface of tested materials. The viability of the cells exposed to 1-, 3-, 5- and 7-day extracts did not change in comparison to the viability of cells cultured in a control medium assayed by an MTT test. Moreover, the flow cytometry analysis of fibroblasts cultured in direct contact with tested alloys revealed that all coatings except TiC did not induce apoptosis or necrosis. Interestingly, 24 hour fibroblast culture on alloys with Ti(C,N) coatings showed that the number of fibroblasts adhered to these alloys, evaluated by scanning electron microscope, increased with an increase in the content of nitrogen in the layer. The present study demonstrates that Ti(C,N) coatings were not cytotoxic and did not induce apoptosis in Ti(C,N) extracts, nor in direct contact with gingival fibroblasts, and can be considered for biomedical applications in the future.
Proceedings of the Society for Experimental Biology and Medicine, Jul 1, 2000
In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the ea... more In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we determined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h. To determine if this rhythm is controlled by nocturnally released hormones, we evaluated the effect of hormones known to be released at night in humans, some of which are also known to be released at night in rats. In humans, prolactin (PRL), growth hormone (GH), and melatonin are known to be released at night, and adrenocorticotropic hormone (ACTH) release is inhibited. In these experiments, conscious rats were injected intravenously with 0.5 ml diluent or the substance to be evaluated just after removal of the first blood sample (0.3 ml), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 microg) produced a rapid increase in plasma leptin that persisted for the duration of the experiment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, alpha bromoergocryptine (1.5 mg), a dopamine-2-receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the decline persisted for 120 min. The minimal effective dose of GH to lower plasma leptin was 1 mg/rat. Insulin-like growth factor (IGF-1) (10 microg), but not IGF-2 (10 microg), also significantly decreased plasma leptin. Melatonin, known to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter leptin release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0. 1-mg dose but produced a delayed, significant increase in leptin, manifest 100-120 min after injection of a 1 mg dose. Since glucocorticoids decrease at night in humans at the time of the maximum plasma concentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of corticosterone following stress in the rat and that glucocorticoids are not responsible for the circadian rhythm of leptin concentration. Therefore, we conclude that an increase in PRL secretion during the night may be responsible, at least in part, for the nocturnal elevation of leptin concentrations observed in rats and humans.
Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasi... more Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and seems to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin, and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA, and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha, (alpha 1) receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor (TNF) alpha. In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP, which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
Proceedings of the National Academy of Sciences of the United States of America, Feb 4, 1997
1028), the authors request that the following be noted. In the ''Materials and Methods'' section ... more 1028), the authors request that the following be noted. In the ''Materials and Methods'' section on page 1024, paragraph 3, line 9, the authors indicate that they used recombinant human leptin. In fact, they used recombinant murine leptin.
Postȩpy higieny i medycyny doświadczalnej, Dec 31, 2017
<jats:p>Membrane lipids, due to diverse molecular structures, electric charge and different... more <jats:p>Membrane lipids, due to diverse molecular structures, electric charge and different functional characteristic, have a profound role in multiple cytophysiological processes. A better understanding of the membrane structure and changes of its function in a wide range of diseases gave rise to a new approach termed membrane lipid therapy and directed to modifying the membranes. The strategies directed to membrane involve a direct regulation of membrane lipid composition that causes a change of the transmembrane protein function and modifies the organization of membrane microdomains, or regulation of enzyme activity and gene expression to alter membrane lipid composition. Membrane therapy assumes the use of new molecules specifically designed to modify lipid composition and function of abnormal signaling proteins. Therefore, modifications of the lipid composition and organization of membrane microdomains become pharmacological targets to reverse pathological changes in the profile of enzymatically and non-enzymatically generated lipid derivatives or to modify signaling pathways in the cell. The present monography is an update of the canonical membrane model by Singer-Nicolson and describes the therapeutic targets related to the regulation of the composition and organization of the lipids in the plasma membrane. </jats:p>
Prostaglandins Leukotrienes and Essential Fatty Acids, Sep 1, 2018
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Fosfolipidy neuronów, zwłaszcza kory mózgu, zawierają dużą ilość wielonienasyconego kwasu dokozah... more Fosfolipidy neuronów, zwłaszcza kory mózgu, zawierają dużą ilość wielonienasyconego kwasu dokozaheksaenowego (DHA, C22: 6n-3). Podstawowym źródłem tego kwasu dla komórek nerwowych jest pokarm oraz synteza DHA w wątrobie i astrocytach z niezbędnego kwasu a-linolowego (C18: 3n-3). Największy przyrost DHA w mózgu obserwuje się w okresie życia płodowego i przez pierwsze dwa lata życia dziecka. Odpowiednia ilość DHA w fosfolipidach błonowych determinuje wiele czynności komórek nerwowych i tym można tłumaczyć wyraźną ochronę DHA w mózgu podczas deficytu kwasu a-linolowego w pożywieniu. Fosfolipidy z acylem DHA są w błonach mobilne, a błony plazmatyczne zbudowane z takich fosfolipidów są cieńsze, bardziej przepuszczalne dla jonów i małych cząsteczek oraz mają luźniejszą strukturę. Te wszystkie cechy błon zwiększają ich "dynamikę" w porównaniu z błonami zbudowanymi z innych fosfolipidów. Ponadto tworzą środowisko dla skondensowanych w błonach neuronalnych białek receptorowych, kanałowych i peryferyjnych. Od dostępności DHA dla neuronów zależy ilość fosfatydyloseryny w wewnętrznej warstwie lipidów błonowych, dzięki której zwiększa się przeżywalność neuronów w wyniku translokacji/aktywacji kinaz Akt i Raf-1/MEK. Obecność DHA w fosfolipidach błonowych ułatwia tworzenie się kompleksu białek v-SNARE/t-SNARE niezbędnego w procesie egzocytozy pęcherzyków synaptycznych i rozrastania się błon wypustek neuronalnych, co determinuje ich plastyczność. DHA odgrywa istotną rolę neuroprotekcyjną. Stwierdzono hamowanie syntezy PGE 2 oraz ekspresji COX-1 w astrocytach hodowanych w obecności DHA, a oksygenazowe metabolity DHA, szczególnie neuroprotektyny D, mogą tłumić reakcje zapalne i zapobiegać uszkodzeniom lub apoptozie neuronów. Skutki obecności DHA w błonach komórek nerwowych i powstających z niego metabolitów, a także funkcje zależnej od DHA fosfatydyloseryny mogą wyjaśniać korzystne działanie suplementacji DHA w poprawie czynności mózgu i w chorobach neurodegeneracyjnych.
Proceedings of the 11th International Joint Conference on Biomedical Engineering Systems and Technologies, 2018
In this paper, an automatic method of neuron nucleuses localization in the images, taken with the... more In this paper, an automatic method of neuron nucleuses localization in the images, taken with the fluorescent microscope, is presented. The proposed approach has two phases. During the first phase, a properly trained convolutional neural network acts as a non-linear filter which indicates regions of interest. The network architecture and specific method of its training are original concepts of the authors of this work. In the second phase, analysis of these regions allows to identify points representing positions of the nucleuses. To illustrate the method, images of neurons isolated from neonatal rat cerebral cortex were used. These images were inspected by a domain expert and all the visible nucleuses were manually annotated. This allowed not only to objectively assess the obtained detection results but it enabled the application of machine learning as well.
Background Astrocytes are responsible for a broad range of functions that maintain homeostasis in... more Background Astrocytes are responsible for a broad range of functions that maintain homeostasis in the brain. However, their response to the pro-inflammatory cytokines released by activated microglia in various neurological pathologies may exacerbate neurodegenerative processes. Accumulating evidence suggests that omega-3 docosahexaenoic fatty acid (DHA) has an anti-inflammatory effect in various cell cultures studies and in a variety of neurological disorders. In this study we examined the mechanism involved in the inhibition of the pro-inflammatory response by DHA in astrocytes treated with IL-1β. Methods and results Activation of the transcription factors NF-κB and AP-1 was measured in IL-1β-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-α and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-κB to the nucleus, significantly lowered...
The fads2 gene encoding Δ6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is exp... more The fads2 gene encoding Δ6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is expressed in astrocytes. Dietary fatty acids, which cross the blood-brain barrier, may regulate the transcription of lipogenic enzymes through activation of transcription factors such as peroxisome proliferator-activated receptors (PPARs). The PPARs form the transcription complex with retinoid X receptors (RXRs) that are activated by 9-cis retinoic acid, a metabolite of vitamin A (VA). The study examines whether challenge of astrocytes with VA, prior 24-h treatment with palmitic acid (PA), α-linolenic acid (ALA) or docosahexaenoic acid (DHA) has the effect on the FADS2 expression. RT-qPCR showed that in astrocytes not challenged with VA, PA increased fads2 gene expression and DHA decreased it. However, in VA-primed astrocytes, PA doubled the FADS2 mRNA levels, while DHA increased fads2 gene expression, oppositely to non-primed cells. Furthermore, similar changes were seen in VA-primed astro...
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