Increased Nerve Growth Factor Levels Research Articles

Levels of BDNF and NGF in adolescent rat hippocampus neonatally exposed to methamphetamine along with environmental alterations.

Neurotrophins are proteins included in development and functioning of various processed in mammalian organisms. They are important in early development but as well as during adulthood. Brain - derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been previously linked with many psychiatric disorders such as depression and addiction. Since during postnatal development, brain undergoes various functional and anatomical changes, we included preweaning environment enrichment (EE), since enrichment has been linked with improved function and development of the several brain structure such as hippocampus (HP), in which we monitored these changes. On the other hand, social isolation has been linked with depression and anxiety-like behavior, therefore postweaning social isolation has been added to this model as well and animal were exposed to this condition till adolescence. We examined if all these three factors had impact on BDNF and NGF levels during three phases of adolescence - postnatal days (PDs) 28, 35 and 45. Our results show that EE did not increase BDNF levels neither in control or MA exposed animals and these results are similar for both direct and indirect exposure. On the other side, social separation after weaning did reduce BDNF levels in comparison to standard housing animals but this effect was reversed by direct MA exposure. In terms of NGF, EE environment increased its levels only in indirectly exposed controls and MA animals during late adolescence. On the other hand, social separation increased NGF levels in majority of animals.

Comparative effect of preoperative oral pregabalin 50 mg vs. 75 mg on nerve growth factor (NGF) levels in parturients undergoing cesarean section

Background & objectives: Postoperative pain after cesarean section (CS) is a crucial problem faced by the parturients. Pregabalin is a choice of preventive analgesia to reduce neuropathic pain, inflammation, tissue irritation, and post-cesarean section pain. The purpose of this study was to compare the effect of giving pregabalin 50 mg or 75 mg in combination with paracetamol 1 g on nerve growth factor (NGF) levels after cesarean section. 
 Methodology: A prospective, comparative model was used in this study. The study took place at Mother and Children Hospital of Sitti Khadijah I, Makassar, Indonesia. A total of 30 patients who underwent CS were randomly divided into two groups; group P1 who received pregabalin 50 mg orally and 1 g paracetamol intravenously, 1 h before surgery (n = 15), and group P2 who received pregabalin 75 mg orally and 1 g paracetamol intravenously, 1 h before surgery (n = 15). Nerve Growth Factor (NGF) levels were measured 2 h before surgery, and at 4 and 6 h post-surgery. Data were analyzed by the Mann-Whitney test using SPSS 26.0.
 Results: There was a decrease in NGF levels in the pregabalin 75 mg group at 6 h post-surgery, while in the pregabalin 50 mg group it tended to increase at 4 and 6 h post-surgery. In the pregabalin 50 mg group, there was a significant increase in NGF levels from measurements of NGF1 to NGF2 and NGF0 to NGF2 (P < 0.05), whereas, in the pregabalin 75 mg group, there was a significant decrease in NGF levels from measurements of NGF1 to NGF2 and NGF0 to NGF2 (P < 0.05). 
 Conclusion: The combination of pregabalin 75 mg orally with paracetamol 1 g intravenously is effective as perioperative multimodal analgesia by reducing nerve growth factor levels after cesarean section surgery.
 Abbreviations: BDNF- brain-derived neurotrophic factor; CS- Cesarean section; GABA- Gamma Amino Butyric Acid; NGF- Nerve Growth Factor
 Keywords: Cesarean section; Nerve Growth Factor (NGF); Postoperative; Pregabalin
 Citation: Ahmad MR, Harahap MW, Wirawan NS. Comparison between pregabalin 50 mg and 75 mg on nerve growth factor (NGF) levels after cesarean section. Anaesth. pain intensive care 2022;27(6):721−725; DOI: 10.35975/apic.v27i6.2159
 Received: February 20, 2923; Revised: July 11,2023; Accepted: October 29, 2023

MP49-05 INTRAVESICAL NERVE GROWTH FACTOR-TARGETING THERAPY USING LIPOSOME-CONJUGATED ANTISENSE IN RATS WITH STRESS-INDUCED BLADDER HYPERSENSITIVITY

You have accessJournal of UrologyCME1 May 2022MP49-05 INTRAVESICAL NERVE GROWTH FACTOR-TARGETING THERAPY USING LIPOSOME-CONJUGATED ANTISENSE IN RATS WITH STRESS-INDUCED BLADDER HYPERSENSITIVITY Tetsuichi Saito, Pradeep Tyagi, Taro Igarashi, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka, and Naoki Yoshimura Tetsuichi SaitoTetsuichi Saito More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Taro IgarashiTaro Igarashi More articles by this author , Tomonori MinagawaTomonori Minagawa More articles by this author , Teruyuki OgawaTeruyuki Ogawa More articles by this author , Osamu IshizukaOsamu Ishizuka More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002624.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Psychological stress has been implicated as an etiological factor of bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC). Also, upregulation of nerve growth factor (NGF) in the bladder, which is detected in BPS/IC patients, is shown to be an important factor inducing bladder hypersensitivity in animal models. Thus. this study investigated the relationship of NGF in the bladder and bladder hypersensitivity caused by psychological stress induced by water avoidance stress (WAS) in rats, and examined whether an intravesical therapy using liposome-conjugated NGF antisense oligonucleotide (OND) can improve the WAS-induced bladder hypersensitive condition. METHODS: Female Wistar rats were used and divided into sham control, WAS and WAS with OND treatment groups. The WAS with OND rats were treated with NGF antisense OND on the day before the first WAS session. After 1-hour WAS or sham sessions once daily for 10 days, the rats were evaluated by cystometry or pain behavior measurements followed by bladder histology. In another set of animals without functional evaluation, the bladder was harvested for molecular studies. RESULTS: Rats exposed to 10-days WAS showed shortened inter-contraction intervals (ICI) and increased pain behaviors, compared to control rats, which were improved with OND treatment (Fig 1-a,b,c). Protein assay showed increased NGF levels in the bladder mucosa in WAS rats, which were decreased by OND treatment (Fig 1-d). RT-PCR showed increases of TRPV1 and TRPA1 and a decrease in Cx43 in the bladder mucosa of WAS rats compared to control rats, which were improved in WAS rats treated with OND (Fig 1-e). Bladder histology revealed urothelial exfoliation in WAS rats, which was recovered with OND treatment (Fig 1-f,g). CONCLUSIONS: Psychological stress induced by WAS elicited bladder hypersensitivity, which was improved by NGF antisense OND treatment. Thus, liposome-based local suppression of upregulated NGF in the bladder could be an effective therapeutic modality for bladder overactivity and enhanced pain sensation induced by psychological stress. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e854 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tetsuichi Saito More articles by this author Pradeep Tyagi More articles by this author Taro Igarashi More articles by this author Tomonori Minagawa More articles by this author Teruyuki Ogawa More articles by this author Osamu Ishizuka More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF DownloadLoading ...

Transcranial direct current stimulation did not revert the increased central and peripheral NGF levels induced by neuropathic pain in rats

ABSTRACT BACKGROUND AND OBJECTIVES: The expression of nerve growth factor (NGF) in the large-size neurons may represent a key role in the neuronal synaptic plasticity and re-organization of neuronal function after a nerve injury. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising tool to pain management since it promotes neuroplasticity in the central system, and it can be combined with other interventions. The aim was to investigate the effects of tDCS in the NGF levels in central and peripheral nervous system structures of rats submitted to a neuropathic pain (NP) model. METHODS: The chronic constriction injury (CCI) of sciatic nerve was used for the induction of NP. For sham surgery, the sciatic nerve was exposed, but without any ligation. The control group did not undergo surgical procedure. After the establishment of NP, treated groups were subjected to tDCS treatment 0.5 mA/20min/day/8 days. NGF levels in cerebral cortex, spinal cord and sciatic nerve were determined by sandwich-ELISA at 48 hours and 7 days after the end of treatment. RESULTS: The CCI model increased NGF levels in all three structures analyzed at long-lasting time, evidencing the importance of this neurotrophin in neuropathic pain condition. On the other hand, there was no tDCS effect in the central and peripheral NGF levels discarding the participation of this neurotrophin in the analgesic tDCS effect. CONCLUSION: tDCS modulation effects of nociceptive pathways seem not to be linked to the NGF signaling in this chronic pain model.

Systemic L-Buthionine -S-R-Sulfoximine Treatment Increases Plasma NGF and Upregulates L-cys/L-cys2 Transporter and γ-Glutamylcysteine Ligase mRNAs Through the NGF/TrkA/Akt/Nrf2 Pathway in the Striatum.

Glutathione (GSH) is the most abundant intracellular antioxidant. GSH depletion leads to oxidative stress and neuronal damage in the central nervous system (CNS). In mice, the acute systemic inhibition of GSH synthesis by L-buthionine-S-R-sulfoximine (BSO) triggers a protective response and a subsequent increase in the CNS GSH content. This response might be modulated by a peripheral increment of circulating nerve growth factor (NGF). NGF is an important activator of antioxidant pathways mediated by tropomyosin-related kinase receptor A (TrkA). Here, we report that peripheral administration of BSO increased plasma NGF levels. Additionally, BSO increased NGF levels and activated the NGF/TrkA/Akt pathway in striatal neurons. Moreover, the response in the striatum included an increased transcription of nrf2, gclm, lat1, eaac1, and xct, all of which are involved in antioxidant responses, and L-cys/L-cys2 and glutamate transporters. Using antibody against NGF confirmed that peripheral NGF activated the NGF/TrkA/Akt/Nrf2 pathway in the striatum and subsequently increased the transcription of gclm, nrf2, lat1, eaac1, and xct. These results provide evidence that the reduction of peripheral GSH pools increases peripheral NGF circulation that orchestrates a neuroprotective response in the CNS, at least in the striatum, through the NGF/TrkA/Akt/Nrf2 pathway.

Photobiomodulation induces antinociception, recovers structural aspects and regulates mitochondrial homeostasis in peripheral nerve of diabetic mice.

Diabetic peripheral neuropathy (DPN) is a nervous disorder caused by diabetes mellitus, affecting about 50% of patients in clinical medicine. Chronic pain is one of the major and most unpleasant symptoms developed by those patients, and conventional available treatments for the neuropathy, including the associated pain, are still unsatisfactory and benefit only a small number of patients. Photobiomodulation (PBM) has been gaining clinical acceptance once it is able to promote early nerve regeneration resulting in significant improvement in peripheral nerves disabilities. In this work, the effects of PBM (660 nm, 30 mW, 1.6 J/cm2 , 0.28 cm2 , 15 s in a continuous frequency) on treating DPN-induced pain and nerve damage were evaluated in an experimental model of diabetic-neuropathy induced by streptozotocin in mice. PBM-induced antinociception in neuropathic-pain mice was dependent on central opioids release. After 21 consecutive applications, PBM increased nerve growth factor levels and induced structural recovery increasing mitochondrial content and regulating Parkin in the sciatic nerve of DPN-mice. Taking together, these data provide new insights into the mechanisms involved in the effects of PBM-therapy emphasizing its therapeutic potential in the treatment of DPN.

Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels

The objective of this study was to verify whether repeated morphine administration and maternal deprivation in early life alter neurobehavioral development and central nerve growth factor (NGF) levels. A total of 58 male Wistar rat pups were used in our study. From postnatal day 1 (P1), litters were daily deprived of their mother for 3h; this was continued for the first 10days of life. Animals were divided into 5 groups: total control (C), did not receive any intervention; saline (S), received saline solution; morphine (M), received morphine; deprived-saline group (DS), were subjected to maternal deprivation and received saline solution; and deprived-morphine (DM), were subjected to maternal deprivation and received morphine. From P8, newborns received subcutaneous (s.c.) injections of morphine or saline (5μg) once daily for 7days. Righting reflex, negative geotaxis and gait were chosen as postural parameters to evaluate neuromotor reflexes. In the righting reflex test, a delay in the development of animals was evidenced in the M group. Performance of negative geotaxis was slower in the M and DM groups. In the gait test, all groups showed a daily improvement in performance in terms of locomotion frequency. An increased frequency of rearing was observed in the M, DS, and DM groups from P16 to P20. The DM group presented an increase in NGF levels in the brainstem. An increase in cerebral cortex NGF levels in the M, DS, and DM groups was observed as well. Our results suggest that changes in environmental conditions and the disruption of mother–infant interactions during the neonatal period can produce changes in the neurobiology, physiology, and emotional behavior of rats. This finding has important implications for the maternal-neonate interaction needed for normal brain development in newborns.

N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson's Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF.

Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days. Animal motor functions were assessed by rotarod test and pole test. Our results showed that PACA ameliorated motor impairments in MPTP-challenged mice. Based on Western blot analysis and/or immunofluorescence staining of NGF and tyrosine hydroxylase (TH), PACA preserved TH levels in the midbrain substantia nigra pars compacta. PACA also increased NGF expression while it decreased proNGF accumulation. Interestingly, NGF was widely induced in the midbrains including astrocytes. To elucidate the mechanisms by which PACA induces NGF, we focused on the effects of PACA on two neurotrophic signaling pathways, the PI3K and MEK pathways. We found that PACA induced the phosphorylation of Akt, ERK, and CREB against MPTP-mediated alterations. Importantly, PACA increased NGF levels and subsequently induced TrkA activation in MPTP-treated mice. Consistently, PACA also increased NGF levels in dopaminergic PC12 cells and primary rat midbrain neurons against N-methyl-4-phenylpyridinium iodide (MPP+) toxicity. ERK and PI3K inhibitors attenuated the effects of PACA on NGF levels. Collectively, our results suggest that PACA may rescue NGF insufficiency via sequential activation of PI3K/Akt, ERK1/2, and CREB signaling pathways. Graphical Abstract ᅟ.

Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain.

Neurotrophic factors: promising candidates in tissue regeneration.

Neurotrophic factors: promising candidates in tissue regeneration.

Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling.

The flower bud of Zingiber mioga Roscoe, known as 'myoga' or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal-regulated kinases and cAMP response element-binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability.

Inhibition of Endothelin Receptors on Sympathetic Innervation via a PI3K/Akt‐dependent Pathway in Post‐infarcted Rats

Although endothelin (ET)-1 has been shown to upregulate nerve growth factor (NGF) expression after myocardial infarction, the molecular mechanisms are largely unknown. We investigated whether selective ET receptor blockers attenuate cardiac sympathetic reinnervation through restoring phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase (GSK)-3β activity. Twenty-four hours after coronary ligation, male Wistar rats were randomized to either vehicle, ABT-627 (an ETA receptorantagonist), or A-192621 (an ETB receptorantagonist) for 4 weeks. Sympathetic hyperinnervation after infarction was confirmed by myocardial norepinephrine measurement and immunofluorescent analysis. This was paralleled by a significant upregulation of NGF protein and mRNA in the vehicle-treated rats, which reduced after administering ABT-627, not A-192621. Arrhythmic scores during programmed stimulation in the vehicle-treated rats were significantly higher than those treated with ABT-627. In an in vivo study NGF was significantly decreased through activation of PI3K/Akt signaling pathway in the presence of ABT-627, which was also confirmed by the ex vivo study showing the increased NGF levels by the use of PI3K inhibitors (wortmannin and LY294002). Furthermore, lithium chloride, an inhibitor of GSK-3β, decreased NGF levels, suggesting the involvement of GSK-3β as a downstream molecule of PI3K/Akt pathways. These data demonstrate that the ETA receptor antagonism is a critical mediator to attenuate sympathetic hyperinnervation probably through the restoration of PI3K/Akt/GSK-3β signaling. Inhibition of GSK-3β-mediated pathways is novel regulators of sympathetic innervation and potential pharmacological targets for arrhythmias.

Transplantation of umbilical cord blood mononuclear cells increases levels of nerve growth factor in the cerebrospinal fluid of patients with autism

We aimed to evaluate the levels of growth factors in the cerebrospinal fluid (CSF) of patients with autism after transplantation of umbilical cord blood mononuclear cells (CBMNCs). Fourteen subjects diagnosed with autism received transplantation of CBMNCs first through intravenous infusion, and three times subsequently through intrathecal injections. A 2-mL sample of CSF was taken before each intrathecal injection. CSF levels of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined by enzyme-linked immunosorbent assay. All data are reported as means ± SD and were analyzed using the SPSS 10.0 software. One-way analysis of variance with post-hoc F-and Q-tests were performed for comparisons. NGF levels in the CSF were significantly increased after transplantation (213.54 ± 56.38 after the third versus 28.32 ± 12.22 ng/L after the first transplantation; P < 0.05), while VEGF and bFGF levels did not change significantly. Therefore, transplantation of CBMNCs could increase NGF levels in the CSF of patients with autism.

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Acute mechanical injury of the human intervertebral disc: link to degeneration and pain.

Excessive mechanical loading or acute trauma to intervertebral discs (IVDs) is thought to contribute to degeneration and pain. However, the exact mechanisms by which mechanical injury initiates and promotes degeneration remain unclear. This study investigates biochemical changes and extracellular matrix disruption in whole-organ human IVD cultures following acute mechanical injury. Isolated healthy human IVDs were rapidly compressed by 5% (non-injured) or 30% (injured) of disc height. 30% strain consistently cracked cartilage endplates, confirming disc trauma. Three days post-loading, conditioned media were assessed for proteoglycan content and released cytokines. Tissue extracts were assessed for proteoglycan content and for aggrecan integrity. Conditioned media were applied to PC12 cells to evaluate if factors inducing neurite growth were released. Compared to controls, IVD injury caused significant cell death. Injury also caused significantly reduced tissue proteoglycan content with a reciprocal increase of proteoglycan content in culture media. Increased aggrecan fragmentation was observed in injured tissue due to increased matrix metalloproteinase and aggrecanase activity. Injured-IVD conditioned media contained significantly elevated interleukin (IL)-5, IL-6, IL-7, IL-8, MCP-2, GROα, and MIG, and ELISA analysis showed significantly increased nerve growth factor levels compared to non-injured media. Injured-disc media caused significant neurite sprouting in PC12 cells compared to non-injured media. Acute mechanical injury of human IVDs ex vivo initiates release of factors and enzyme activity associated with degeneration and back pain. This work provides direct evidence linking acute trauma, inflammatory factors, neo-innervation and potential degeneration and discogenic pain in vivo.

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis.

Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis, and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems. Thus, the objective of this study is to evaluate the neuronal calcium sensor (NCS-1) and dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) expression as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in prefrontal cortex and hippocampus of rats 12, 24, and 48 h after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation procedure. After 12 and 24 h, there was an increase of NGF levels in hippocampus; and up to 48 h, a decrease of NCS-1 expression in prefrontal cortex, a decrease of BDNF levels in hippocampus and an increase of NGF levels in hippocampus. In conclusion, we believe that the low expression of NCS-1 in prefrontal cortex and low levels of BDNF in hippocampus may be associated with the pathophysiology of cognitive impairment during sepsis and a putative role of the dopaminergic system.

Effect of Nerve Growth Factor on the In Vitro Induction of Apoptosis of Human Conjunctival Epithelial Cells by Hyperosmolar Stress

To evaluate the effects of nerve growth factor (NGF), which is activated during inflammatory episodes of ocular diseases, on the apoptotic response in cultured human primary conjunctival epithelial cells (pHCECs). Levels of NGF transcripts and NGF protein in pHCEC grown in medium with normal osmolarity (307 mOsm/L) or hyperosmolar medium (350, 400, and 450 mOsm/L) were determined using RT-PCR or ELISA, respectively. To assess apoptosis, pHCEC were cultured in normal or 400 mOsm/L hyperosmolar medium with neutralizing anti-NGF antibody or recombinant human NGF for 6 hours before analysis by flow cytometry. Levels of Bcl-xL, Bax, phosphorylated JNK, and cleaved caspase-3 were detected using Western blotting. Levels of the inflammatory cytokine IL-6 was analyzed using ELISA. Hyperosmolar conditions increased NGF levels in cultured pHCECs. Hyperosmolarity and exposure to neutralizing anti-NGF antibody significantly increased the number of apoptotic cells. Addition of recombinant human NGF to 400 mOsm/L medium decreased the number of apoptotic cells, reduced the expression of phosphorylated JNK, Bax, and cleaved caspase-3 and increased the expression of Bcl-xL. Levels of IL-6 were increased by hyperosmotic stress but decreased by exposure to recombinant human NGF. Hyperosmolarity induces apoptosis of pHCECs by activating JNK signaling. Increased levels of NGF under hyperosmolar conditions may contribute, at least in part, to the reduced apoptosis of pHCECs and may be beneficial in recovering conjunctival damage due to chronic hyperosmolar stress.

Genotoxicity profile of erinacine A-enriched Hericium erinaceus mycelium

Hericium erinaceus (H. erinaceus) has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF) from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo. With increasing recognition of erinacine A in H. erinaceus (EAHE) mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests) according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions.

Nerve growth factor (NGF) levels in follicular fluid of infertile patients undergoing to in vitro fertilization (IVF) cycle

Objective: The aim of this study was to determine the levels of NGF in follicular fluid and serum samples, and to correlate them with some characteristics of the patients (age) and of the IVF protocol (E2 levels, number of collected oocytes, used FSHr IU) to investigate its rule in the folliculogenesis.Methods: This study examined a sample of 78 women undergoing to FIVET/ICSI cycles since October 2011 to March 2013. NGF levels were determinated in follicular fluid (FF) and serum sample using enzyme immunoassay ELISA kit for NGF.Results: The NGF level was significantly higher in FF (213.76 pg/ml) than in basal serum (46.47 pg/ml (p < 0.001) and in serum sample of the pick-up day (60.75 pg/ml (p < 0.001). In FF, the levels of NGF were positively correlated to age of women (corr.coeff. r = 0.44) and units of FSHr used during stimulation protocol (corr.coeff r = 0.34).Discussion: Our results demonstrate that the FF levels are higher than the blood; so there is a local production of NGF in the ovarian follicle, important for the follicle’s growth and oocyte quality. We could also say that the increase of NGF levels is correlated to a lower ovary response, that is obviously less in the older women.

Effect of Acute and Chronic Administration of l-Tyrosine on Nerve Growth Factor Levels in Rat Brain

Most inborn errors of tyrosine catabolism produce hypertyrosinemia. Neurological manifestations are variable and some patients are developmentally normal, while others show different degrees of developmental retardation. Considering that current data do not eliminate the possibility that elevated levels of tyrosine and/or its derivatives may have noxious effects on central nervous system development in some patients, the present study evaluated nerve growth factor (NGF) levels in hippocampus, striatum and posterior cortex of young rats. In our acute protocol, Wistar rats (10 and 30days old) were killed 1h after a single intraperitoneal administration of L-tyrosine (500mg/kg) or saline. Chronic administration consisted of L-tyrosine (500mg/kg) or saline injections 12h apart for 24days in Wistar rats (7days old); the rats were killed 12h after the last injection. NGF levels were then evaluated. Our findings showed that acute administration of L-tyrosine decreased NGF levels in striatum of 10-day-old rats. In the 30-day-old rats, NGF levels were decreased in hippocampus and posterior cortex. On the other hand, chronic administration of L-tyrosine increased NGF levels in posterior cortex. Decreased NGF may impair growth, differentiation, survival and maintenance of neurons.