The Infona portal uses cookies, i.e. strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser.
Injuries to the central nervous system can affect the blood-brain barrier (BBB), including disruption and influencing peptide transport across the BBB. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent neurotrophic and neuroprotective peptide currently being investigated for its therapeutic role following injury to the central nervous system and can cross the BBB in a saturable...
The demonstration that peptides and regulatory proteins can cross the blood–brain barrier (BBB) is one of the major contributions of Dr. Abba J. Kastin. He was the first to propose that peptides could cross the BBB, the first to show that an endogenous peptide did so, and the first to describe a saturable transport system at the BBB for peptides. His work shows that in crossing the BBB, peptides and...
Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent neurotrophic and neuroprotectant that is transported across the blood–brain barrier in amounts sufficient to affect brain function. However, its short half-life in blood makes it difficult to administer peripherally. Here, we determined whether the radioactively labeled 38 amino acid form of PACAP can enter the brain after intranasal...
In recent years, there have been a large number of neuropeptides discovered that regulate food intake. Many of these peptides regulate food intake by increasing or decreasing nitric oxide (NO). In the current study, we compared the effect of the food modulators ghrelin, NPY and CCK in NOS KO mice. Satiated homozygous and heterozygous NOS KO mice and their wild type controls were administered ghrelin...
Insulin detemir has a different profile of action on the central nervous system (CNS) than human insulin. It has been hypothesized that this is caused by an altered ability of insulin detemir to cross the blood–brain barrier (BBB). Here, we measured the permeability of the BBB to insulin detemir. We labeled insulin detemir with radioactive iodine (I-Det) and examined its ability to cross the BBB of...
Human ghrelin is transported across the blood–brain barrier (BBB) of normal mice. Here, we studied the effects of triglycerides, obesity, and starvation in retired breeder mice maintained on a high fat diet, mice age-matched to the retired breeders but maintained on normal chow, and 8-week-old mice maintained on breeder chow. The rate of ghrelin transport across the BBB was studied by both the intravenous...
Nesfatin-1 has recently been identified as a hypothalamic and brain stem peptide that regulates feeding behavior. Here, we determined the ability of nesfatin-1 to cross the blood–brain barrier (BBB) of mice. We used multiple-regression analysis to determine that radioactively labeled nesfatin-1 injected intravenously entered the brain. The entry rate (K i ) of 131 I-nesfatin-1 from...
The amyloid hypothesis states that amyloid beta protein (Aβ) plays a major causal role in the onset of Alzheimer's disease. Toxicity of Aβ can be modified by metal ions. Two mechanisms by which such Aβ and metal ions could interact are by enhanced oxidative stress or by altered fibrillation. Specifically, Aβ fibrillation is increased by aluminum (Al) and copper (Cu) and Al also increases Aβ uptake...
The level of Met-enkephalin in the brain is inversely correlated with ethanol consumption and is controlled partially through efflux activity of peptide transport system-1 (PTS-1) at the blood–brain barrier (BBB). Prolonged alcohol drinking can perturb aspects of this system, including a loss of control of Met-enkephalin levels at the transcriptional and translational levels, and impaired release...
Leptin is a peptide hormone secreted by adipose tissue. Studies have shown that leptin crosses the blood–brain barrier (BBB) by a saturable transport system where it acts within the hypothalamus to regulate food intake and energy expenditure. Leptin also acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor-mediated transmission. This suggests...
Antisense potentially can manipulate target gene expression in the brain if it can cross the blood–brain barrier (BBB). We designed three (10mer, 17mer, and 19mer) phosphorothioated antisenses (PS-ODNs) directed against the precursor molecule of methionine enkephalin (Met-Enk), an opiate peptide which suppresses voluntary ethanol drinking. We measured the ability of the antisenses to cross the BBB,...
Orexin-A is a peptide produced in the lateral hypothalamus/perifornical area, which stimulates feeding. The production of orexin-A is determined by the metabolic state of the animal. We have previously shown that nitric oxide (NO) plays an important role as a mediator of feeding induced by a variety of neuropeptides. This raises the question of whether orexin-A's effects are NO dependent. Here, we...
Antibodies directed against amyloid beta protein (AßP) have been suggested to be effective in the treatment of Alzheimer's disease (AD). Here, we used in vivo and in vitro models to test some of the mechanisms by which antibodies may produce their effects. We found that the blood-to-brain uptake of murine AßP1–42 was significantly reduced when co-injected peripherally with an antibody known to reverse...
Leptin is a 16,000-Da protein which is secreted by fat but acts within the brain to regulate adiposity. Our Peptides Classic addressed the mystery of how such a large molecule could negotiate the blood-brain barrier (BBB), a structure which normally excludes proteins from the brain. We found that leptin was transported across the BBB by a saturable transport system. This finding was important to understanding...
Most evidence agrees that levels of methionine enkephalin (Met-Enk) in brain are inversely correlated with ethanol drinking and withdrawal seizures. One area of discrepancy is the effect of chronic ethanol administration on the level of immunoactive Met-Enk in brain, with some authors reporting increased and others reporting decreased levels. These reports differed greatly in terms of method of ethanol...
Ghrelin is a newly discovered gastric peptide, which has orexigenic effects. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and stimulates growth hormone and gastrointestinal motility. We have previously shown that nitric oxide (NO) plays an important role as a mediator of feeding induced by a variety of neuropeptides. This raises the question of whether ghrelin's effects...
We investigated the ability of vasoactive intestinal peptide (VIP) to cross the blood–brain barrier (BBB), the interface between the peripheral circulation and central nervous system (CNS). VIP labeled with 131I (I-VIP) and injected intravenously into mice was taken up by brain as determined by multiple-time regression analysis. Excess unlabeled VIP was unable to impede the entry of I-VIP, indicating...
The blood-brain barrier (BBB) controls the exchange of peptides and regulatory proteins between the central nervous system (CNS) and the blood. Transport across the BBB of such regulatory substances is altered in animal models of Alzheimer's disease. These alterations could lead to cognitive impairments or diminish their therapeutic potential. Here, we measured the transport rate of radioactively...
Vaccinations against amyloid β protein (AβP) reduce amyloid deposition and reverse learning and memory deficits in mouse models of Alzheimer's disease. This has raised the question of whether circulating antibodies, normally restricted by the blood-brain barrier (BBB), can enter the brain [Nat. Med. 7 (2001) 369-372]. Here, we show that antibody directed against AβP does cross the BBB at a very low...
Orexin-A is an endogenous peptide with receptors present throughout the brain. Here, we examined the effect of post-training administration of orexin-A on retention in active and passive avoidance. Orexin-A administered by intracerebroventricular (i.c.v.) injection to CD-1 mice post-training improved retention in both T-maze footshock avoidance and one trial step-down passive avoidance. SAMP8 mice...
Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.