Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus.

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps.

Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice.

Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer's disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus.

Reduced Cholinergic Activity in the Hippocampus of Hippocampal Cholinergic Neurostimulating Peptide Precursor Protein Knockout Mice.

The cholinergic efferent network from the medial septal nucleus to the hippocampus has an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to efficiently encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP) induces acetylcholine synthesis in medial septal nuclei.

Enhancement of long-term potentiation via muscarinic modulation in the hippocampus of HCNP precursor transgenic mice.

Hippocampal cholinergic neurostimulating peptide (HCNP) regulates acetylcholine synthesis in the septal hippocampus through the quantitative increase of choline acetyltransferase levels in the septal nucleus both in vitro and in vivo. Additionally, HCNP-precursor protein transgenic (HCNP-pp Tg) mice display depressive behavior. To examine the physiological function of HCNP and/or HCNP-pp on hippocampal neural activity, we investigated whether overexpression of HCNP-pp strengthened the efficiency of neural activity in the hippocampus.

Differences in dopaminergic modulation to motor cortical plasticity between Parkinson's disease and multiple system atrophy.

Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS.

Phosphorylation of collapsin response mediator protein-2 regulates its localization and association with hippocampal cholinergic neurostimulating peptide precursor in the hippocampus.

Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in the medial septal nucleus in vitro and in vivo. The precursor, HCNP-pp, is a multifunctional protein participating in important signaling pathways, such as MAPK/ERK kinase (MEK) and G-protein-coupled receptor kinase 2 (GRK2). We recently demonstrated that HCNP-pp colocalizes with collapsin response mediator protein-2 (CRMP-2) at presynaptic terminals in the hippocampus, suggesting that HCNP-pp may play an important role in presynaptic function in association with CRMP-2.

Co-localization of hippocampal cholinergic neurostimulating peptide precursor with collapsin response mediator protein-2 at presynaptic terminals in hippocampus.

Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in medial septal nucleus in vitro and in vivo. HCNP precursor protein (HCNP-pp) is a multifunctional protein that participates in a number of signaling pathways, including MAPK/extracellular signal and G-protein-coupled receptor kinase 2. We recently demonstrated that the amount of collapsin response mediator protein-2 (CRMP-2) is increased in hippocampus of HCNP-pp transgenic mice.

Suppression of astrocyte lineage in adult hippocampal progenitor cells expressing hippocampal cholinergic neurostimulating Peptide precursor in an in vivo ischemic model.

Hippocampal cholinergic neurostimulating peptide (HCNP) is known to promote differentiation of septohippocampal cholinergic neurons. The HCNP precursor protein (HCNP-pp) may play several roles, for example, as an ATP-binding protein, a Raf kinase inhibitor protein, and a phosphatidylethanolamine-binding protein, as well as a precursor for HCNP. This study therefore aimed to elucidate the involvement of HCNP-pp in specific neural lineages after stroke using a hypoxic-ischemic (HI) rat model of brain ischemia.

Changes in striatal dopamine release associated with human motor-skill acquisition.

The acquisition of new motor skills is essential throughout daily life and involves the processes of learning new motor sequence and encoding elementary aspects of new movement. Although previous animal studies have suggested a functional importance for striatal dopamine release in the learning of new motor sequence, its role in encoding elementary aspects of new movement has not yet been investigated. To elucidate this, we investigated changes in striatal dopamine levels during initial skill-training (Day 1) compared with acquired conditions (Day 2) using (11)C-raclopride positron-emission tomography.

Temporary deterioration of executive function after subthalamic deep brain stimulation in Parkinson's disease.

Objective: Selective impairment of executive function has been shown in Parkinson's Disease (PD) patients undergoing Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). However, some patients experience difficulties in daily life, such as dissension in interpersonal relationships or a loss of lifestyle balance, in the short term after surgery. Our hypothesis is that these difficulties might be related to executive dysfunction.

Plaque vulnerability in internal carotid arteries with positive remodeling.

Background: This study aimed to evaluate the efficacy of assessing positive remodeling for predicting future stroke events in the internal carotid artery. We therefore assessed narrowing of the carotid artery lumen using multidetector-row computer tomography (MDCT) angiography and carotid plaque characteristics using black-blood (BB) magnetic resonance (MR).

Methods: We retrospectively selected 17 symptomatic and 11 asymptomatic lesions with luminal narrowing >50%.

Suppressed phosphorylation of collapsin response mediator protein-2 in the hippocampus of HCNP precursor transgenic mice.

We previously reported a novel peptide, Hippocampal Cholinergic Neurostimulating Peptide (HCNP), which induces acetylcholine synthesis by increasing the amount of choline acetyltransferase (ChAT) in medial septal nuclei. The HCNP precursor protein (HCNP-pp), composed of 186 amino acids, is an inhibitory factor of the c-Raf/MEK cascade and may be involved in fetal rat brain development via the inhibition of phosphorylation of Erk. To clarify the involvement of HCNP in hippocampal cholinergic circuitry, we previously generated HCNP-pp transgenic (HCNP-pp Tg) mice using the promoter of the α subunit of Ca(2+) calmodulin-dependent protein kinase II (CaMKIIα).

HCNP precursor protein transgenic mice display a depressive-like phenotype in old age.

We have previously reported a novel peptide, hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine synthesis by increasing the amount of cholineacetyltransferase (ChAT) in medial septal nuclei. The HCNP precursor protein, composed of 186 amino acids, is an inhibitory factor of the c-Raf/ MEK cascade and may be involved in the development of the fetal rat brain via the inhibition of Erk phosphorylation. To clarify the involvement of HCNP in hippocampal cholinergic circuitry, we previously generated HCNP precursor protein (HCNP-pp) transgenic mice using the promoter of the alpha subunit of Ca(2+) calmodulin-dependent protein kinase II (CaMKIIalpha).

Impaired ability to shift weight onto the non-paretic leg in right-cortical brain-damaged patients.

Background: : Stroke patients experience postural instability that can impede functional improvements in their gait. However, the precise functions of the dominant and non-dominant hemispheres in controlling static standing posture and weight-bearing remain unclear.

Objective: : To investigate differences in balancing ability between right-handed patients with right and left hemispheric lesions.

Directed neural lineage differentiation of adult hippocampal progenitor cells via modulation of hippocampal cholinergic neurostimulating peptide precursor expression.

Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from young rat hippocampus, has been known to promote the differentiation of septo-hippocampal cholinergic neurons. Recently, the precursor protein of HCNP (HCNP-pp) has also received attention as a multifunctional protein with roles, in addition to serving as the HCNP precursor, such as acting as an ATP-binding protein, a Raf kinase inhibitor protein (RKIP), and phosphatidylethanolamine-binding protein (PEBP). In particular, the function of RKIP has attracted attention over several years for its role in controlling cellular proliferation and metastasis in cancer cells.

[Lambert-Eaton myasthenic syndrome associated with pulmonary squamous cell carcinoma and circulating anti-P/Q-type voltage-gated calcium channel antibody].

We report a 64-year-old man diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) associated with pulmonary squamous cell carcinoma. Circulating anti-P/Q-type voltage-gated calcium channel (VGCC) antibody was detected, and the patient was treated with 3,4-diaminopyridine. At age 61, chest radiograph revealed a tumor shadow in the right upper lung field.

Overexpression of hippocampal cholinergic neurostimulating peptide in heterozygous transgenic mice increases the amount of ChAT in the medial septal nucleus.

Acetylcholine modulates neural activity in the hippocampal glutamatergic pathway via the induction of phosphorylated Erk and may act as a novel transmitter in septohippocampal memory formation. However, how acetylcholine synthesis in the septal nucleus is regulated is unknown. We have purified a peptide from the hippocampus of the young adult rat, named hippocampal cholinergic neurostimulating peptide (HCNP) that induces acetylcholine synthesis in vitro in the septal nucleus.

Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke.

Background: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.

Predicting the motor outcome of acute disseminated encephalomyelitis by apparent diffusion coefficient imaging: Two case reports.

We present two cases of young adults with acute disseminated encephalomyelitis (ADEM) who developed severe conscious and motor disturbances. Despite their similar initial clinical course and MRI findings, their motor function outcomes were quite different. In both cases, fluid attenuated inversion recovery (FLAIR) sequenced MRI showed multiple symmetric hyperintense lesions in the internal capsule and the brainstem at the subacute stage.

[Case of paraneoplastic limbic encephalitis associated with malignant B cell lymphoma].

We report a case of a 62-year-old man with limbic encephalitis associated with diffuse large B cell lymphoma. He was hospitalized for the assessment of cognitive disturbance and changes in characteristics. Neurological examination revealed disturbance of recall and recent memory.

Analysis of DNA variations in promoter region of HCNP gene with Alzheimer's disease.

Hippocampal cholinergic neurostimulating peptide (HCNP), which enhances acetylcholine synthesis and induces cholinergic phenotype development of the septohippocampal system, is derived from HCNP precursor protein (HCNPpp), also known as phosphatidylethanolamine binding protein (PEBP) and Raf kinase inhibitor protein (RKIP). Our previous study demonstrated that expression of HCNPpp mRNA was decreased in the hippocampi of autopsied brains of Alzheimer's disease (AD) patients, indicating the association of HCNP with the pathogenesis of AD. To clarify the involvement of gene variations in the promoter region of the gene encoding HCNPpp in this mRNA reduction, we analyzed DNA polymorphisms or mutations within this gene promoter region in AD patients by direct sequencing.