Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.


:This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans.


Brain Res


Brain research


Anderson BM,Jacobson L,Novakovic ZM,Grasso P




Has Abstract


2017-06-01 00:00:00












  • The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra).

    abstract::Following infection with influenza virus, animals display decreased locomotor activity and feeding behavior and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), induced by the infe...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Swiergiel AH,Smagin GN,Johnson LJ,Dunn AJ

    更新日期:1997-11-21 00:00:00

  • Release and spread of immunoreactive neurokinin A in the cat spinal cord in a model of acute arthritis.

    abstract::Antibody microprobes were used to study the release of immunoreactive neurokinin A into the spinal cord of anaesthetised cats during and following injection of a knee joint with kaolin and carrageenan. A basal level of immunoreactive neurokinin A was detected prior to any noxious stimuli. Innocuous mechanical joint st...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Hope PJ,Jarrott B,Schaible HG,Clarke RW,Duggan AW

    更新日期:1990-11-19 00:00:00

  • Neurochemical and behavioral effects of bupropion and mecamylamine in the presence of nicotine.

    abstract::The primary mechanism of action of bupropion, a smoking cessation drug, is commonly believed to involve the dopaminergic system although evidence exists that bupropion also has effects at nicotinic acetylcholine receptors (nAChRs). This study evaluated the disruptive effects of nicotine on response rates in the presen...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Vann RE,Rosecrans JA,James JR,Philibin SD,Robinson SE

    更新日期:2006-10-30 00:00:00

  • Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats.

    abstract::The characterization of motor and cognitive dysfunctions following a neonatal ischemic injury is a prerequisite to investigate putative pharmacological interventions. To this end, in the present study, we evaluated the long-lasting behavioral alterations occurring after a hypoxic/ischemic injury obtained by the combin...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Balduini W,De Angelis V,Mazzoni E,Cimino M

    更新日期:2000-03-24 00:00:00

  • Ultrastructural study of motor endings on long chain intrafusal fibers in muscle spindles of the cat.

    abstract::Five complete poles of long nuclear chain intrafusal fibers of cat tenuissimus muscle spindles embedded in a plastic medium were cut in serial, 1 micron thick transverse sections and stained with toluidine blue. Each fiber pole displayed one plate-type motor ending positioned outside the encapsulated part of the spind...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Kucera J,Hughes R

    更新日期:1983-03-07 00:00:00

  • Disinhibition of the rostral ventral medulla increases blood pressure and Fos expression in bulbospinal neurons.

    abstract::The GABA agonist muscimol, injected into the depressor area of the caudal ventrolateral medulla, increased blood pressure and increased the expression of the immediate early gene c-fos in the rostral ventral medulla (RVM) of the rat. The number of Fos-immunoreactive (Fos-IR) neurons seen in the RVM was increased 3-fol...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Minson JB,Llewellyn-Smith IJ,Arnolda LF,Pilowsky PM,Oliver JR,Chalmers JP

    更新日期:1994-05-16 00:00:00

  • Rab3A deletion selectively reduces spontaneous neurotransmitter release at the mouse neuromuscular synapse.

    abstract::Rab3A is a synaptic vesicle-associated GTP-binding protein thought to be involved in modulation of presynaptic transmitter release through regulation of vesicle trafficking and membrane fusion. Electrophysiological studies at central nervous system synapses of Rab3A null-mutant mice have indicated that nerve stimulati...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Sons MS,Plomp JJ

    更新日期:2006-05-17 00:00:00

  • Hippocampal grafts into the intact brain induce epileptic patterns.

    abstract::Spontaneous hippocampal EEG activity and evoked field potentials were investigated in intact rats and in animals with fetal hippocampal grafts. Pieces of hippocampal grafts, derived from 15- to 16-day-old fetuses, were used to prepare cell suspensions and grafted directly into the intact hippocampus. Control animals r...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Buzsáki G,Masliah E,Chen LS,Horváth Z,Terry R,Gage FH

    更新日期:1991-07-19 00:00:00

  • Reflex responses of human thigh muscles to non-noxious sural stimulation during stepping.

    abstract::An investigation of reflex responses of leg muscles to sural stimulation during stepping was performed on human subjects. Non-noxious electrical stimulation applied during the swing phase or the latter half of the stance phase produced a mixed increase and decrease of EMG activity in the hamstring muscles. No response...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Kanda K,Sato H

    更新日期:1983-12-12 00:00:00

  • Hemorrhage induces c-fos immunoreactivity in spinally projecting neurons of cat subretrofacial nucleus.

    abstract::Neuronal expression of c-fos product in the cat rostral ventrolateral medulla was studied by immunohistochemistry. Spinally projecting neurons of the subretrofacial (SRF) nucleus were pre-labeled by retrograde transport of fluorescent latex microspheres from the lumbar cord. In 3 animals which were bled by approximate...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: McAllen RM,Badoer E,Shafton AD,Oldfield BJ,McKinley MJ

    更新日期:1992-03-20 00:00:00

  • Studies on the relationship between Ca2+ efflux from mitochondria and the release of amino acid neurotransmitters.

    abstract::It is known that transmitter release depends upon the entry of calcium ions into the synaptic terminal. Mitochondria have been suggested to play a key role on the regulation of intracellular Ca2+ concentration, thereby influencing transmitter liberation and synaptic transmission. Here we report the stimulatory effect ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Sandoval ME

    更新日期:1980-01-13 00:00:00

  • Effects of early destruction of the mouse arcuate nucleus by monosodium glutamate on age-dependent natural killer activity.

    abstract::The present study has examined the effect on age-dependent natural killer (NK) cell cytotoxic (NKCC) activity after the destruction of the arcuate nucleus (AR) of the hypothalamus in newborn mice with the neurotoxin monosodium glutamate (MSG). The NKCC activity was determined at different ages from the 18th day to the...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Belluardo N,Mudò G,Bindoni M

    更新日期:1990-11-26 00:00:00

  • Spontaneous voltage and current fluctuations in tissue cultured mouse dorsal root ganglion cells.

    abstract::Fetal mouse dorsal root ganglion (DRG) neurons were maintained in primary dissociated cell culture for periods of 7 days to 3 months. Intracellular recordings from these cells revealed the presence of spontaneous subthreshold potentials in 101/177 neurons studied. When measured at the resting membrane potential, these...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Mathers DA,Barker JL

    更新日期:1984-02-13 00:00:00

  • Electrophysiological and morphological studies on thalamic neurons receiving entopedunculo- and cerebello-thalamic projections in the cat.

    abstract::Electrophysiological studies on the entopedunculo- and cerebello-thalamic projections were performed by intracellular recordings in the thalamic VA, VL and VM nuclei of cats under sodium pentobarbital anesthesia. Identification of the thalamic neurons were performed electrophysiologically by antidromic activation on s...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Yamamoto T,Noda T,Miyata M,Nishimura Y

    更新日期:1984-06-03 00:00:00

  • Effects of transcranial magnetic stimulation on muscle activation patterns and joint kinematics within a two-joint motor synergy.

    abstract::We studied the effects of transcranial magnetic stimulation (TMS) on muscle activation patterns and joint kinematics during oscillatory movements of a joint within a two-joint (elbow-wrist) synergy. Healthy young adults (N=8) performed cyclic movements in one of the joints while the other joint was or was not involved...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Latash ML,Danion F,Bonnard M

    更新日期:2003-01-31 00:00:00

  • Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata.

    abstract::We examined the expression of IL-6 in the substantia nigra pars reticulata (SNr) at various time points after transient (3 h) middle cerebral artery occlusion (MCAO) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for immunohistochemistry with antibodie...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Dihné M,Block F

    更新日期:2001-01-19 00:00:00

  • Dye and electrical coupling between frog motoneurons.

    abstract::Coupling between lumbar motoneurons in the isolated frog spinal cord was studied by using intracellular recordings and intracellular injections of Lucifer Yellow CH. Physiological studies revealed intra- and intersegmental, short latency electrical interactions between many motoneurons. Injections of Lucifer Yellow in...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Brenowitz GL,Collins WF 3rd,Erulkar SD

    更新日期:1983-09-12 00:00:00

  • Intracellular recordings from serotonergic dorsal raphe neurons: pacemaker potentials and the effect of LSD.

    abstract::Intracellular recordings in vivo from serotonergic dorsal raphe neurons of the rat brain reveal that these cells undergo a pronounced postspike hyperpolarization followed by a gradual interspike depolarization leading to the succeeding spike. Such repetitive cycles of interspike hyperpolarization and depolarization, w...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Aghajanian GK,Vandermaelen CP

    更新日期:1982-04-29 00:00:00

  • Bax and Bcl-2 expression and TUNEL labeling in lumbar enlargement of neonatal rats after sciatic axotomy and melatonin treatment.

    abstract::Peripheral axotomy in neonatal rats induces neuronal death. We studied the anti-apoptotic protein Bcl-2 and cell death promoter Bax in spinal cord of neonatal rats after sciatic transection and treatment with melatonin, a neuroprotective substance. Pups were unilaterally axotomized at P2 and received melatonin (1 mg/k...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Rogério F,Jordão H Jr,Vieira AS,Maria CC,Santos de Rezende AC,Pereira GA,Langone F

    更新日期:2006-09-27 00:00:00

  • Somatostatin inhibition of adenylate cyclase activity in different brain areas.

    abstract::Somatostatin receptors have been identified in different brain areas but the characterization of their postreceptor effect is still lacking. In this study we analyze the somatostatin effect on adenylate cyclase activity in different brain regions, namely frontal cortex, striatum, hypothalamus and hippocampus. Somatost...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Schettini G,Florio T,Meucci O,Landolfi E,Grimaldi M,Ventra C,Marino A

    更新日期:1989-07-17 00:00:00

  • Glutamate and capsaicin effects on trigeminal nociception II: activation and central sensitization in brainstem neurons with deep craniofacial afferent input.

    abstract::We examined the effect of the peripheral application of glutamate and capsaicin to the temporomandibular joint (TMJ) in influencing the activation and central sensitization of TMJ-responsive nociceptive neurons in the trigeminal subnucleus caudalis/upper cervical cord (Vc/UCC). The activity of single neurons activated...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Lam DK,Sessle BJ,Hu JW

    更新日期:2009-02-09 00:00:00

  • Responses of pallidal neurons to striatal stimulation in intact waking monkeys.

    abstract::Extracellular single-unit activity was recorded from neurons of the internal and external pallidal segments, and from 'border cells' at the periphery of the segments, in 3 waking cynomolgus monkeys during electrical stimulation of 3 sites bilaterally in the striatum: one in the caudate nucleus and two in the putamen. ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Tremblay L,Filion M

    更新日期:1989-09-25 00:00:00

  • Increased iron in the substantia nigra of 6-OHDA induced parkinsonian rats: a nuclear microscopy study.

    abstract::The trace elemental concentrations, including iron, in the substantia nigra (SN) of a 6-OHDA induced rat model of Parkinson's disease were measured using nuclear microscopy. Only rats that exhibited amphetamine induced rotation of more than 7 turns/min were used. The results showed that the iron levels were significan...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: He Y,Thong PS,Lee T,Leong SK,Shi CY,Wong PT,Yuan SY,Watt F

    更新日期:1996-09-30 00:00:00

  • Electrophysiological correlates of the efficient detection of emotional facial expressions.

    abstract::Behavioral studies have shown that emotional facial expressions are detected more rapidly and accurately than are neutral expressions. However, the neural mechanism underlying this efficient detection has remained unclear. To investigate this mechanism, we measured event-related potentials (ERPs) during a visual searc...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Sawada R,Sato W,Uono S,Kochiyama T,Toichi M

    更新日期:2014-04-29 00:00:00

  • Localization of cholinesterase activity in the outer plexiform layer of the larval tiger salamander retina.

    abstract::Acetylcholinesterase activity, which may be indicative of cholinergic synapses, has been ultrastructurally localized in the outer plexiform layer of the larval tiger salamander retina using the cholinesterase staining method of Karnovsky and Roots. In the presence of the butyrylcholinesterase inhibitor, ethopropazine,...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Hutchins JB,Polans AS,Werblin FS

    更新日期:1984-02-06 00:00:00

  • Resting hippocampal blood flow, spatial memory and aging.

    abstract::Aging is accompanied by a general deterioration of fluid cognitive processes and a reduction in resting cerebral blood flow (CBF). While the two phenomena have been observed independently, it is uncertain whether individual differences in cerebral blood flow are reliably associated with cognitive functioning in older ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Heo S,Prakash RS,Voss MW,Erickson KI,Ouyang C,Sutton BP,Kramer AF

    更新日期:2010-02-22 00:00:00

  • Calcium channel types mediating synaptic transmission during aging.

    abstract::The effects of omega-conotoxin (CTX) GVIA, omega-agatoxin (Aga) IVA, and the dihydropyridine nicardipine were studied on synaptic transmission in the hippocampus during aging. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region in slices from young and aged Fischer 344 rats. Peptide toxin...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Hall SC,Griffith WH

    更新日期:1997-01-16 00:00:00

  • Leucine-enkephalin-containing neuron system in the facial nucleus of the rat with special reference to its fine structure.

    abstract::The light and electron microscopic localization of leucine-enkephalin-containing terminals in the facial nucleus of the rat were investigated by means of the peroxidase-antiperoxidase (PAP) immunocytochemical technique. By light microscopy, leucine-enkephalin-like immunoreactive (LEI) terminals were unevenly distribut...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Senba E,Tohyama M

    更新日期:1983-09-05 00:00:00

  • The recovery of blood-nerve barrier in crush nerve injury--a quantitative analysis utilizing immunohistochemistry.

    abstract::The purpose of this study is to reveal whether the application of immunohistochemical examinations to the peripheral nervous system (PNS) can be a reliable method for the quantitative analysis of the blood-nerve barrier (BNB) and the relationship between restoration of BNB and nerve regeneration. Sciatic nerves in rat...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Omura K,Ohbayashi M,Sano M,Omura T,Hasegawa T,Nagano A

    更新日期:2004-03-19 00:00:00

  • Cathepsin L is involved in 6-hydroxydopamine induced apoptosis of SH-SY5Y neuroblastoma cells.

    abstract::Our previous study reported that cathepsin L may contribute to the death of dopaminergic neurons in rodent model of Parkinson's disease (PD). In this study we detected the changes in the expression of lysosomal cathepsin L in cellular models of PD. In human neuroblastoma SH-SY5Y cells, treatment with 6-hydroxydopamine...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Xiang B,Fei X,Zhuang W,Fang Y,Qin Z,Liang Z

    更新日期:2011-04-28 00:00:00