Kenji Yoshimi

Juntendo University · Department of Neurophysiology

While dopamine (DA) may be clearly detected by voltammetric techniques such as fast-scan cyclic voltammetry (FSCV) in the heavily-innervated striatum, the differentiation of DA from other monoamines, including norepinephrine (NE) and serotonin (5-HT), is crucial for further applications outside of the striatum. We show that using normal pulse volta...

Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of co...

In-vivo voltammetry has successfully been used to detect dopamine release in rodent brains, but its application to monkeys has been limited. We have previously detected dopamine release in the caudate of behaving Japanese monkeys using diamond microelectrodes (Yoshimi 2011); however it is not known whether the release pattern is the same in various...

Voltammetric recording of dopamine (DA) with fast-scan cyclic voltammetry (FSCV) on carbon fiber microelectrodes have been widely used because of its high sensitivity to dopamine. However, since an electric double layer on carbon fiber surface in physiological ionic solution behaves as a capacitor, fast voltage manipulation in FSCV induces large ca...

Significance Dopamine (DA) neurons in the ventral tegmental area (VTA) react to aversive stimuli mostly by transient silencing. It remains unclear whether this reaction directly induces aversive responses in behaving mice. We examined this question by optogenetically controlling DA neurons in the VTA and found that the inactivation of DA neurons re...

The in vitro and in vivo electrochemical detection of the reduced form of glutathione (L-γ-glutamyl-L-cysteinyl-glycine, GSH) using boron doped diamond (BDD) microelectrode for potential application in the assessment of cancerous tumors is presented. Accurate calibration curve for the determination of GSH could be obtained by the in vitro electroch...

Supporting information

A new method is proposed for the accurate and reproducible detection of dopamine using cyclic voltammetry on boron-doped diamond (BDD) electrode. It is shown that reproducible voltammograms can be obtained when applying a relatively high scan rate (100 V s−1) during the detection measurements. For lower scan rates (1 V s−1), it is proven that elect...

Reward-induced burst firing of dopaminergic neurons has mainly been studied in the primate midbrain. Voltammetry allows high-speed detection of dopamine release in the projection area. Although voltammetry has revealed presynaptic modulation of dopamine release in the striatum, to date, reward-induced release in awakened brains has been recorded on...

parkin is the most frequent causative gene among familial Parkinson's disease (PD). Although parkin deficiency induces autosomal recessive juvenile parkinsonism (AR-JP, PARK2) in humans, parkin knockout (PKO) mice consistently show few signs of dopaminergic degeneration. We aimed to directly measure evoked extracellular dopamine (DA) overflow in th...

The rotarod test is widely used to evaluate the motor coordination of rodents, and is especially sensitive in detecting cerebellar dysfunction. However, mice with striatal dopamine depletion show only mild or no motor deficit on the typical accelerating rotarod. This suggests that dopamine-depleted mice are useful as animal models for non-motor sym...

Reward presentation is known to induce transient bursts of midbrain dopamine neurons in monkeys and rats, and the reward-induced dopamine overflow has been detected in the rat ventral striatum. To detect reward-related dopamine release in the dorsal striatum of behaving mice (C57BL/6), we used voltammetry with carbon-fiber microelectrodes implanted...

In vivo voltammetry is a valuable technique for rapid measurement of dopamine in the brain of freely behaving rats. Using a conventional voltammetry system, however, behavioural freedom is restricted by cables connecting the head assembly to the measurement system. To overcome these difficulties, we developed a wireless voltammetry system utilizing...

Highly boron-doped diamond (BDD) was deposited on chemically etched micrometer-sized tungsten wires using microwave plasma assisted chemical vapor deposition (MPCVD), and these were used to fabricate BDD microelectrodes. BDD microelectrodes with very small diameter (about 5 microm) and 250 microm in length could be made successfully. In addition to...

Neuronal function and innervation density is regulated by target organ-derived neurotrophic factors. Although cardiac hypertrophy drastically alternates the expression of various growth factors such as endothelin-1, angiotensin II, and leukemia inhibitory factor, little is known about nerve growth factor expression and its effect on the cardiac sym...

The I93M mutation in ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) was reported in one German family with autosomal dominant Parkinson's disease (PD). The causative role of the mutation has, however, been questioned. We generated transgenic (Tg) mice carrying human UCHL1 under control of the PDGF-B promoter; two independent lines were generated...

We developed a new method for comparing immunopositive cell densities across groups of animals and creating statistical parametric maps on standardized sections. As an example, we compared Iba-1 (microglial marker) positive cell densities in rats with (n=6) and without (n=6) unilateral injection of 1-methyl-4-phenylpyridinium salt (MPP+). Immunopos...

Oxidative stress is involved in the degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD). Vitamin E (alpha-tocopherol) is a potent antioxidant in the cell membrane that can trap free radicals and prohibit lipid peroxidation. The retention and secretion of vitamin E are regulated by alpha-tocopherol transfer protein (TTP...

A method for estimating three-dimensionally DTM (Digital Terrain Model) and DCHM (Digital Canopy Height Model) from range data measured by a portable scanning Lidar was examined. This method is expressed by (1) measurement of ground and tree canopy from nine points using a portable scanning Lidar, (2) transformation from polar coordinate to orthogo...

Remote sensing is an effective technique for assessing effects of air pollution and global change on forests. Thus, several types of remote sensing, such as Landsat TM and helicopter-borne scanning Lidar have been applied for this purpose. While these techniques were proven to be effective, ground truth measurements are also necessary for determini...

Recent studies of enhanced hippocampal neurogenesis by antidepressants suggest enhancement of neurogenesis is a potentially effective therapy in neurodegenerative diseases. In this study, we evaluated nigral neurogenesis in animals and autopsy brains including patients with Parkinson's disease (PD). First, proliferating cells in substantia nigra we...

The present study was designed to elucidate the inflammatory and apoptotic mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a model of Parkinson's disease. Our results showed that mutant mice lacking the caspase-11 gene were significantly more resistant to the effects of acute treatment with MPTP than their...

A significant number of brain neurons in the rabbit brain were immunostained with anti-rabbit gamma-immunoglobulin (IgG). IgG-positive neurons were often found in the cerebellum, lower brainstem and motor nuclei. Similar IgG-positive neurons were occasionally found in the hippocampus, cerebral cortex and midbrain, but not in the striatum and thalam...

Although possible usefulness of non-selective monoamine oxidase (MAO) inhibitors for Parkinson's disease therapy has been suggested in the literature, MAO inhibitors whose inhibition is reversible and have dual action to both MAO-A and -B subtypes is not available yet. Subtype selectivity and reversibility of a series of novel MAO inhibitors, 3-(2-...

To elucidate molecular mechanisms in learning and memory, we analyzed expression of mRNAs in brains of rabbits undergoing eyeblink conditioning. Infusion of the transcription inhibitor actinomycin D into the cerebellar interpositus nucleus reversibly blocked learning but not performance of the conditioned response. Differential display PCR analysis...

Senile plaques are a pathological hallmark of Alzheimer's disease. The major component of senile plaques is β-amyloid which consists of approximately 4000 mol. wt of peptide. Accumulating evidence suggests that β-amyloid may represent the underlying cause of Alzheimer's disease. In vitro, β-amyloid has been shown either to be directly neurotoxic or...

The avoidance behavior of rats in a typical step-through passive avoidance task was evaluated by using two types of time measurements that differed from traditional step-through latency (STL). The total stay-time in the light box (TL) was calculated as an index of the dark box avoidance throughout the retention trial, counting the time before and a...

The mechanism underlying the change in clathrin immunohistochemistry preceding delayed neuronal death (DND) was studied in gerbils. The ischaemic change observed with chc5.9 anti-clathrin antibody in hippocampal CA1 was initially ameliorated by pentobarbital, which blocks DND, but 1 day after ischaemia, no change in the immunoreactivity of the SDS-...

Clathrin, which constitutes coated vesicles and plays important roles in neuronal functions, has been reported to be involved in the pathology of Alzheimer's disease. In the brains of the patients with Pick's disease, distribution of clathrin was immunohistochemically investigated using monoclonal antibodies binding to different epitopes of clathri...

Clathrin, which constitutes coated vesicles, plays important roles in neuronal functions. In the brains of the patients with Alzheimer's disease, distribution of clathrin was immunohistochemically investigated using four monoclonal antibodies against clathrin light chains, LCB.1, LCB.2, X-16 and CON.1, to study the involvement of clathrin in the pa...

Clathrin, which constitutes coated vesicles, plays important roles in neuronal functions. In the brains of the patients with Alzheimer's disease, distribution of clathrin was immunohistochemically investigated using four monoclonal antibodies against clathrin light chains, LCB.1, LCB.2, X-16 and CON.1, to study the involvement of clathrin in the pa...

Changes in MAP2 and clathrin immunoreactivity were studied in gerbil hippocampus after transient cerebral ischemia. MAP2 immuno-reactivity decreased significantly by 1 h in the subiculum-CA1 and CA2 areas which correspond to reactive change, while no decrease was observed in CA1 until day 4. Before the initiation of delayed neuronal death, MAP2 imm...