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Biomedical subjects

Naoko Nonaka

Publications and source records attributed to Naoko Nonaka.

13 recordsLinked to original sources
PubMed2006

Ghrelin controls hippocampal spine synapse density and memory performance.

The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes.

Animals↗
PubMed2006

Morphometric development of the posterior funicular nucleus in the human medulla oblongata.

Using serial sections of 11 human brains of fetuses 18-40 weeks of gestation (WG), 2-month-old infant and 63-year-old adult, we conducted the quantitative analysis of the development of the posterior funicular nucleus (PFN) in the medulla oblongata. The results suggest the following: (1) The cells of the human cuneatus lateralis nucleus are easily distinguished from those of the gracilis nucleus and cuneatus medialis nucleus because the neuronal somatic areas are the largest; the smallest neuronal areas are in the cuneatus medialis nucleus. (2) The development of the PFN occurs at least in four stages characterized by the degree of maturation of the neurons: (a) immature neuronal stage before 20 WG, (b) preparatory stage between (a) and (c), (c) accelerated development stage from 30 to 40 WG, and (d) postnatal stage. The development of the human posterior funicular nucleus accelerates after 30 WG, and postnatal qualitative maturation also occurs. Developmental differences of the three nuclei of the PFN in the medulla oblongata are presented and discussed from the morphological and morphometric point of view.

Humans↗
PubMed2005

Effect of lipopolysaccharide on the transport of pituitary adenylate cyclase activating polypeptide across the blood-brain barrier.

Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective effects against ischemia, even when given by intravenous (iv) administration 24 h after stroke. Transport of PACAP across the blood-brain barrier (BBB) by peptide transport system (PTS)-6 underlies its effectiveness after iv administration. However, PACAP transport is modified after central nervous system (CNS) injury, raising the question of whether cytokines or BBB disruption affects PTS-6 activity. Lipopolysaccharide (LPS) is derived from bacterial cell walls and affects the passage of other proteins across the BBB through its release of cytokines and disruption of the BBB. Here, we examined by several methods the transport of radioactively labeled PACAP (I-PACAP) across the BBB after intraperitoneal (ip) injection of LPS. After three doses of LPS, studies at a single time point found a differential effect of LPS on the brain/serum ratio for I-PACAP and radioactively labeled albumin (I-Albumin). Whereas LPS increased the ratio for I-Albumin, demonstrating BBB disruption, it decreased the ratio for I-PACAP. Multiple-time regression analysis, capillary depletion, and brain perfusion showed that this decrease was fully explained by a decrease in the initial, reversible binding of I-PACAP to brain endothelium, while the rate of transport of PACAP into the brain was not altered. These methods also showed that the LPS-treated mice were volume contracted. This volume contraction concentrated the amount of I-PACAP in the blood and so increased the amount of I-PACAP presented to the BBB. Lack of change in transport rate combined with volume contraction resulted in a net increase of about 30% of the iv dose of I-PACAP entering the brain. LPS did not alter the efflux of I-PACAP from the CNS. In conclusion, PTS-6 remains active and should be able to deliver therapeutic amounts of PACAP to the CNS in brain injuries involving cytokine release and BBB disruption.

Animals↗
PubMed2005

Morphometric comparison of human nerve cells: special sensory system.

We compared morphometric data on various nerve cells in the human special sensory system using the modified Klüver-Barrera staining method with an extremely minimized shrinkage ratio and an image-analyzer. According to the measurement data of cell-body sizes, we classified nerve cells of the various nerve nuclei in the special sensory system into three groups. These data are of interest to better understand the process of nerve conduction in the special sensory system.

Afferent Pathways↗
PubMed2005

Morphometric comparison of human nerve cells: pyramidal motor system.

We compared morphological and morphometric data on various motor neurons in the human pyramidal system using the modified Klüver-Barrera staining method with extremely minimized shrinkage ratio and an image-analyzer. We classified motor neurons in the human pyramidal system into three groups according to the measurement data. This report may be of interest to better understand the process of nerve conduction in the human pyramidal system.

Female↗
PubMed2004

Development of the human cuneatus medialis nucleus: a morphometric evaluation.

The morphometric features of the development of the human cuneatus medialis nucleus (CMN) were examined using complete serial celloidin sections of 11 brains: nine fetal brains, the brain of a 2-month-old infant and that of a 63-year-old adult. The morphometric analysis revealed at least four stages in the development of the CMN characterized by the maturation of neurons: (1) immature neuronal stage, (2) preparatory stage, (3) accelerated development stage and (4) postnatal stage. The development of the human CMN accelerates after 32 weeks of gestation (WG), and postnatal qualitative maturation also occurs. From the viewpoint of morphometric evaluation, the CMN gradually matures between 18 and 40 WG without a rapid growth phase as far as we have observed.

Female↗
PubMed2004

Effects of lipopolysaccharide on leptin transport across the blood-brain barrier.

Leptin is a 16-kDa protein secreted by fat cells and transported into the brain where it decreases appetite and increases body temperature. Leptin transport is saturable and regulated by epinephrine, triglycerides, and starvation. Lipopolysaccharide (LPS) is derived from bacterial cell walls and also decreases appetite and increases body temperature. LPS is known to increase leptin levels in serum and to affect the passage of other regulatory proteins across the blood-brain barrier (BBB). Here, we examined the ability of LPS, at doses which induce weight loss, to modify the BBB transport of radioactive leptin (I-Lep). The transport rate of intravenously injected I-Lep was decreased by 50-60% from 8 to 12 h after a single i.p. injection of LPS (3 mg/kg). The effect of LPS was dose-dependent. In comparison to the brain/serum ratio, the baseline cerebrospinal fluid (CSF)/serum ratio for I-Lep was much lower and not inhibited by LPS. LPS did not affect I-Lep transport when studied by the brain perfusion method nor was Ob-Ra mRNA expression in isolated brain microvessels altered, demonstrating that a circulating factor rather than altered BBB function was responsible for inhibition. Brain perfusion showed that LPS was not this factor. Serum leptin was doubled and serum triglycerides increased by 44% after LPS administration, suggesting these to be the circulating inhibitory factors. In conclusion, a single dose of LPS has long-lasting effects on the transport of serum leptin across the BBB that are likely mediated through self-inhibition and triglycerides.

Analysis of Variance↗
PubMed2003

Characterization of blood-brain barrier permeability to PYY3-36 in the mouse.

Peptide YY3-36 (PYY) has emerged as an important signal in the gut-brain axis, with peripherally administered PYY affecting feeding and brain function. For these effects to be direct, PYY would have to cross the blood-brain barrier (BBB). Here, we determined the permeability of the BBB to PYY radioactively labeled with 131I (I-PYY). Multiple-time regression analysis showed the unidirectional influx rate (Ki) from blood-to-brain for I-PYY to be 0.49 +/- 0.19 microl/g-min, a rate similar to that previously measured for leptin. Influx was not inhibited by 1 microg/mouse of unlabeled PYY, suggesting PYY crosses the BBB by transmembrane diffusion. About 0.176% of the i.v.-injected dose of I-PYY was taken up by brain, an amount similar to that for other peptides important in gut-brain communication. Capillary depletion showed that 69% of I-PYY crossed the BBB to enter the parenchymal space of the brain, and high-performance liquid chromatography demonstrated that the radioactivity in this space represented intact I-PYY. After intracerebroventricular injection, I-PYY crossed from brain to blood by the mechanism of bulk flow. We conclude that PYY crosses in both the blood-to-brain and brain-to-blood directions by nonsaturable mechanisms. Passage across the BBB provides a mechanism by which blood-borne PYY can affect appetite and brain function.

Animals↗
PubMed2003

Differences in the axonal compositions of the human mandibular nerve between dentulous and edentulous jaws.

We examined the human mandibular nerve to find differences in the composition of nerve fiber axons between dentulous and edentulous jaws Using Goto's modification of Masson-Goldner's method. We discovered that the edentulous jaw did not contain any large size axons, compared with the dentulous jaw. This can be considered as evidence that the larger fibers innervating the periodontal ligament decreased degenerated after tooth loss.

Aged↗
PubMed2002

Development of the human lateral cuneate nucleus: a morphometric evaluation.

The morphometric development of the human lateral cuneate nucleus was examined in nine fetuses and neonates at 18-40 weeks of gestation, a 2-month-old infant and a 63-year-old adult. The authors observed serial sections of the brain containing lateral cuneate nucleus and measured the volume of nuclear column and the number, cell body area and perimeter of neurons using a microscope with a drawing tube and an image-analyzing computer system. A morphometric evaluation revealed that a turning point in the development of the human lateral cuneate nucleus occurring at 30 WG, as this marks the beginning of a gradual increase in the average area and average perimeter; And it is the point at which the neuropil index suddenly increases sharply, to fall back down to lower levels afterwards. The establishment of a neuronal connection between the lateral cuneate nucleus and the cerebellum, which is necessary for proper performance of movements in the upper part of the body.

Afferent Pathways↗
PubMed2002

Regional differences in PACAP transport across the blood-brain barrier in mice: a possible influence of strain, amyloid beta protein, and age.

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 labeled pituitary adenylate cyclase-activating polypeptide (PACAP) from blood into whole brain and into 11 brain regions in three groups of mice: young (2 months old) ICR, young (2 months old) SAMP8, and aged (12 months old) SAMP8 mice. The SAMP8 is a strain which develops impaired learning and memory with aging that correlates with an age-related increase in brain levels of amyloid beta protein (A beta P). PACAP is a powerful neurotrophin that may have a therapeutic role in neurodegenerative diseases. We found that I-PACAP crossed the BBB fastest at the hypothalamus and the hippocampus in all three groups. Slower transport rates into the whole brain, the olfactory bulb, the hypothalamus, and the hippocampus for aged SAMP8 mice was likely related to differences both from strain and expression of A beta P with aging.

Aging↗
PubMed2002

Passage of amyloid beta protein antibody across the blood-brain barrier in a mouse model of Alzheimer's disease.

Vaccinations against amyloid beta protein (A beta P) 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 A beta P does cross the BBB at a very low rate. Entry is by way of the extracellular pathways with about 0.11% of an intravenous (i.v.) dose entering the brain by 1h. Clearance of antibody from brain increasingly dominates over time, but antibody is still detectable in brain 72 h after i.v. injection. Uptake and clearance is not altered in mice overexpressing A beta P. This ability to enter and exit the brain even in the presence of increased brain ligand supports the use of antibody in the treatment of Alzheimer's and other diseases of the brain.

Aging↗