The effects of 1 Hz rTMS over the hand area of M1 on movement kinematics of the ipsilateral hand

1 Hz rTMS applied over primary motor cortex (M1) reduces cortical excitability outlasting the stimulation period. Healthy right-handed subjects performed finger and hand tapping and a reach-to-grasp movement prior to (baseline) and after 1 Hz rTMS applied over (1) M1 of either the right or the left hemisphere, and (2) the vertex (control stimulation). 1 Hz rTMS applied over the left M1, but not over the vertex, improved movement kinematics of finger and hand tapping as well as grasping with the left hand. 1 Hz rTMS applied over the right M1, but not over the vertex, improved only the kinematics of hand tapping performed with the right hand. These data suggest that 1 Hz rTMS induced inhibition of ipsilateral M1 reduces transcallosal inhibition of contralateral M1 and thereby improves motor performance at the ipsilateral hand. The impact on motor performance of the ipsilateral hand is most pronounced after 1 Hz rTMS over the left M1.     

Expression pattern of neuregulin-1 type Ⅲ during the development of the peripheral nervous system

Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinating fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods(such as the premyelinating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various developmental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-1 type III m RNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating(from postnatal day 2 to postnatal day 5) and myelinating stage(from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage(after postnatal day 10).     

Is activation of the metabotropic glutamate receptors impaired in the hippocampal CA1 area of the aged rat?

The effects of aging on activation of metabotropic glutamate (mGlu) receptors were studied in the CA1 field of hippocampal slices from young (3- to 4-month-old) and aged (24- to 27-month-old) Sprague-Dawley rats with the use of ex vivo electrophysiological recording techniques. The depolarization of membrane potential, the increase in input resistance, and the blockade of the afterhyperpolarization induced in pyramidal cells of young rats by bath application of the mGlu receptor agonist (±)-trans-1-aminocyclopentate-1,3-dicarboxylic acid were not altered in aged animals. No age-related changes of the depressive effects of the mGlu receptor agonist were found on either the excitatory glutamatergic postsynaptic potential or the GABA-mediated inhibitory postsynaptic potentials induced by the stimulation of the stratum radiatum. The magnitude of synaptic plasticity involving mGlu receptor activation, although weaker, was not significantly altered in aged rats. This absence of age-related effects on activation of mGlu receptors may be important in understanding the possible origins of the alterations in neuronal plasticity which occur in brain aging. Hippocampus 1997;7:455–459. © 1997 Wiley-Liss, Inc.     

Expression of the Newly Identified Gene CAC1 in the Hippocampus of Alzheimer’s Disease Patients

Alzheimer's disease (AD), the most common form of senile dementia, is associated with neurodegeneration. The development of Alzheimer's disease is related to abnormalities of cell cycle regulation. Preliminary work showed that a novel gene, CAC1, was highly expressed in tumors and had an oncogene-like function related to cell cycle regulation. The pathogenesis of AD is still incompletely understood. In this study, we measured the expression level of CAC1 in the hippocampus of AD patients to explore the involvement of CAC1 in the development of AD. Our findings showed that the expression level of CAC1 in the hippocampus of AD patients was significantly lower than that of normal controls. The reduction of CAC1 expression did not affect tau/p-tau-396, amyloid precursor protein or apolipoprotein E4 in the in vitro model. A reduction of cyclin E was detected after a CAC1-knockdown. Interestingly, we found that the knockdown of CAC1 by RNAi led to an increase in oxidative stress and the level of p53 protein in SHSY-5Y cells. The expression of CAC1 in SHSY-5Y cells protected the cells from apoptosis induced by Aβ toxicity or oxidative stress. These results established that CAC1 is an important factor for the protection of cells against Aβ toxicity and oxidative stress.     

The role of DJ-1 in the pathogenesis of Parkinson’s disease

1 Introduction Parkinson’s disease (PD) is a common neurodegen- erative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars com- pacta (SNpc). Although the majority of the cases appear to be sporadic, the disorder also can be associated with spe- cific genetic defects, several of which have been identified, including α-synuclein, parkin, PINK1, dardarin (LRRK2) and DJ-1[1]. Vincenzo Bonifati et al. localized a gene for autosomal recessive…     

The role of synphilin-1 in the pathogenesis of Parkinson’s disease

1 Introduction Parkinson’s disease (PD) is the second most common neurological disorder to affect approximate 0.2% of overall population and 2% of those over the age of 65. The disease is characterized by a triad of cardinal symptoms, including bradykinesia (slowed movement), resting tremor, and rigidity. Progressive degeneration of the dopaminergic (DAergic) neurons which are mostly located in the sub- stantia nigra pars compacta (SNpc), and the formation of eosinophilic inclusions known a…     

The role of synphilin-1 in the pathogenesis of Parkinson＇s disease

Parkinson＇s disease （PD） is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic （DAergic） neurons in the substantia nigra and the appearance of Lewy bodies （LBs）, whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin- 1, α-synuclein and park：in. Synphilin- 1 is an α-synuclein-binding protein and a major component of LBs, It is widely accepted that synphilin- 1 is involved in the pathogenic process of PD. This review will provide an overall view of the role of synphilin- 1 in the pathogenesis of Parkinson＇ s disease and the latest findings in this field.     

Alzheimer's disease-related loss of Pin1 function influences the intracellular localization and the processing of AβPP

Increased amyloidogenic processing of the amyloid-β protein precursor (AβPP) is a characteristic of Alzheimer's disease (AD). We previously observed that the prolyl isomerase Pin1, which is down-regulated in AD, regulates AβPP conformation accelerating cis/trans isomerization of the phospho-Thr668-Pro669 peptide bond, and that Pin1 knockout in mice increases the amyloidogenic processing of AβPP, although the underlying mechanism is still unknown. Since the intracellular localization of AβPP determines whether the processing will be amyloidogenic or non-amyloidogenic, here we addressed the question whether loss of Pin1 function affects the intracellular localization of AβPP, influencing AβPP processing. Using cellular models of Pin1 knockout and Pin1 knockdown, we have demonstrated that lowering Pin1 levels changed the intracellular localization and the processing of AβPP. Under these conditions, less AβPP was retained at the plasma membrane favoring the amyloidogenic processing, and the kinetics of AβPP internalization increased as well as the nuclear trafficking of AβPP C-terminal fragment AICD. In addition, AβPPThr668Ala mutant, which cannot bind to Pin1 and retains more trans conformation, rescued the levels of AβPP at the plasma membrane in Pin1 knockout cells. Thus, loss of Pin1 function contributes to amyloidogenic pathways, by facilitating both the removal of AβPP from compartments where it is mostly non-amyloidogenic and its internalization to more amyloidogenic compartments. These data suggest that physiological levels of Pin1 are important to control the intracellular localization and metabolic fate of Thr668-phosphorylated AβPP, and regulation of AβPP conformation is especially important in pathologic conditions of AβPP hyperphosphorylation and/or loss of Pin1 function, associated with AD.     

A case of Guillain-Barré syndrome with bulbar palsy showing the elevations of the anti-GD1a and GT1b antibodies]

We reported a 44-year-old woman with Guillain-Barré syndrome (GBS) showing elevations of serum anti-GD1a and anti-GT1b antibody levels. A few days after an upper respiratory infection, she felt numbness in her hands and feet, dysphagia and dysarthria, and weakness in her limbs. On admission, examination showed the paralysis of pharynx and neck, moderate weakness of face and upper limbs, and mild weakness of lower limbs. Sensory deficits were minimal on the distal side of extremities. Deep reflexes were decreased or absent. Laboratory examinations revealed the albumino-cytological dissociation in cerebrospinal fluid and the increase of anti-GD1a and anti-GT1b antibodies in serum. Nerve conduction studies demonstrated axonal damage to the motor nerves. With immunoadsorption therapy, she gradually recovered and the anti-GD1a and anti-GT1b antibodies were normalized. It was reported that the anti-GT1a antibody may be associated with a pharyngeal-cervical-brachial (PCB) variant of GBS (Ropper) and the similar cases including the present case. However, in the present case, the serum anti-GT1a antibody level was not increased, whereas those of anti-GD1a and anti-GT1b antibodies did. Therefore, these antibodies may also play a role in the development of PCB signs in GBS.     

The role of D J-1 in the pathogenesis of Parkinson＇s disease

Parkinson＇s disease （PD） is a slowly progressive neurodegenerative disorder characterized clinically by bradykinesia, rigidity, tremor, gait dysfunction, and postural instability. Several genes have been identified for monogenic disorders that variably resemble Parkinson＇s disease. Here, we focus on PARK7, a gene relates to an autosomal recessive form of early-onset Parkinsonism and encodes a protein named DJ- 1. Though the exact role of D J- 1 needs to be elucidated, it is generally thought to be functioned as a molecular chaperone and an oxidative sensor （or antioxidative factor）. We will review the protective role of DJ- 1 to prevent dopaminergic neurons in the substantia nigra pars compacta （SNpc） from degeneration and how its dysfunction would lead to neurodegeneration.     

Localization of angiotensin II (AT1)-receptor-immunoreactive fibres in the hypothalamus of rats: angiotensin II-sensitive tanycytes in the ependyma of the third ventricle?

Scanning the hypothalamus of rats for receptor binding sites of the octapeptide hormone angiotensin II (ANG II), we observed ANG II-sensitive fibres in the ventrolateral hypothalamus. The ANG II (AT(1))-receptor-immunoreactive processes originate from cells-probably tanycytes-embedded in the base and the ventrolateral walls of the third ventricle and reach into the retrochiasmatic area, the ventrolateral hypothalamus and the median eminence.     

What is the role of the cerebellum in the pathophysiology of dystonia?

Journal of Neurology -     

Does the place of treatment influence the quality of life of schizophrenics?

OBJECTIVE: Chronically mentally ill patients in community mental health care report a better quality of life (QOL) than those in long-term hospital care, which suggests that the treatment setting per se influences their QOL. METHOD: In a region where both treatment settings are of a comparable high standard, we assessed the QOL of 96 schizophrenic patients from these two treatment settings, and the factors which most influenced their QOL. RESULTS: Community-care patients reported a better QOL than long-term hospital-care patients. However, when other factors influencing QOL were included in a regression analysis, the place of treatment was no longer significant, but rather the social support, the severity of the illness, educational level and certain illness concepts. CONCLUSION: It is probably not the place per se which influences the QOL, but apart from personal, sociodemographic and illness-related factors, the amount of social support that is provided in different settings.