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CNS Diseases
The most common central nervous system (CNS) diseases include stroke, traumatic brain injury, drug addiction, Alzheimer's disease, Parkinson's disease, anxiety, depression and etc. This group of diseases constitutes one of the biggest social, healthy and financial problems for human being. To fight against these diseases is currently an extensive focus in the fields. By combining experience/expertise from both pharmaceutical industry and academia, we provide valuable services to accelerate the drug discovery for the treatment
of these devastating disorders.
Animal models of CNS diseases
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Alzheimer's disease (AD):
Genetically modeling in the mouse: Expression of a human mutant gene or a BAC
fragment that is associated with a familial type of AD
Pharmacologically/neurosurgically modeling in the rat: Ventricular infusion of
β-amyloid with an Osmotic mini pump
Fig. 1. An AD model in the mouse: A. Wild-type mice. B. AD mice without β-amyloid deposition. C. AD mice with β-amyloid deposition. D and E. Double staining of β-amyloid deposition. F. I. and L. Wild-type mice. G and H. Neurofibrillary tangle-like structure in AD mice. J and K. tau pathology in AD mice. M. Neuronal degeneration and N. tau pathology in AD model mice.
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Age-dependent neurodegeneration:
Conditional double knockout PS1/PS2 in the mouse: which shows age-dependent neuronal loss and many other AD-like pathologies such as tau
hyperphosphorylation, neurofibrillary tangle-like structure, and dementia
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Parkinson’s Disease (PD):
Genetic model in the mouse: Expression of a mutant gene that is associated with a familial autosomal-dominant mutation, or knockout of a gene that is associated with a familial autosomal-recessive mutation for PD
Pharmacological/neurosurgical model in the rat: Unilateral intra-striatal injection of 6-OHDA to lesion nigro-striatal dopamine neurons
Pharmacological/neurosurgical model in the monkey: Systemic administration of MTPT to lesion dopamine neurons (under development)
Fig. 2. PD modeling. A. Neurosurgery for microinjection of 6-OHDA in the rat. B. Forelimb deficits of contralateral forelimb at 6 weeks after surgery C. Quantitative analysis of rotation number after an Apomorphine challenge. D. Quantitative analysis of motor function with a rotarod test. Data are expressed as mean ± SD.
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Depression:
Restraint stress in the mouse
Tail suspension in the mouse
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Anxiety:
Genetic model in the mouse: Overexpression of the cholecystokinin receptor-2 (CCKR-2) in the forebrain
Various stress paradigms: early-life stress, chronic stress, or acute stress
PTSD model in the mouse: combination of genetic manipulation and environmental stress
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Schizophrenia/bipolar disorder:
PCP model in the mouse and rat
Sleep-deprivation in the rat
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Drug addiction:
Behavioral sensitization
Drug of abuse-induced conditioned place preference (CPP)
Reinstatement of extinguished CPP
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Amnesic model:
Various compounds such as ketamine-, scopolamine-induced amnesia in the rat and mouse
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Mental retardation model
BDNF knockdown in the mouse
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Stroke/ischemia model:
Middle cerebral artery occlusion (MCAO) in the rat
Forebrain ischemia model in the gerbil
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Traumatic brain injury model
Weight-dropping in the mouse
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Huntington’s disease model
Genetic model in the mouse: Expression of a mutant Huntington gene
Pharmacological/neurosurgical model in the rat: Striatal microinjection of quinolinic acid or 3-NY in the rat
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Pain model:
Nociceptive pain produced by peripheral injection of formalin or capsaicin
Inflammatory pain induced by carrageenan
Neuropathic pain induced by sciatic nerve ligation, spinal nerve ligation, or streptozotocin-induced diabetic neuropathy
Postoperative pain induced by a plantar incision
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Animal models for studies of the blood-brain barrier (BBB)
Experimental approaches
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Behavioral studies
Learning and memory: Morris water
maze (spatial learning and memory,
working memory, reference memory,
reversal learning, hippocampus-
dependent memory); Barnes maze
(spatial learning and contextual
conditioning (hippocampus-dependent),
cued conditioning (hippocampus-
independent), long-term memory, short-
term memory, amygdala-dependent
memory, fear response.
Fig. 3. Morris water maze
Motor function: Rotarod test, open-field test, walking-beam test, treadmill test
 
(under development).
Anxiety-like behavior: Elevated-plus maze, fear-conditioning test, open-field
 
behavior, startle response, and social interaction.
Depression-like behavior: Novelty-induced hypophagia, tail suspension test,
forced swim test, open-field behavior, social interaction, and learned
helplessness.
Schizophrenia/bipolar-like behavior: Pre-pulse inhibition (PPI; under
development), working memory, locomotion/motor activity, social interaction,
aggressive/mania-like behavior, forced swim test, and nesting behavior.
Drug addictive behavior: Drug-seeking behavior (self-administration; under
 
development), behavioral sensitization, conditioned place preference (CPP), and
 
CPP extinction.
Pain-related behavior: hot-plate, tail flick (infrared heat/pressure).
Homecage behavior and environmental enrichment.
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Pharmacological/molecular/biochemical assay
Distributional and quantitative analysis of gene expression at the mRNA and
protein levels: real-time RT-PCR, microarray, in situ hybridization, Western blot,
immunostaining, and ELISA.
in vivo and in vitro isotope-labeled ligand binding/incorporation assay: receptor
binding assay, autoradiography
Brain regional drug delivery (stereotaxic microinjection) and chronic brain
regional drug delivery (Osmotic mini-pump micro-infusion)
Spatial and temporal epigenetic analysis: histone modification, DNA methylation,
and genome-wide DNA methylation profile.
Microdialysis (under development)
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Histological/morphological studies
Gross brain morphometry
Colorimetric staining: Nissl staining
(neuron), LFB staining (glial myelin), Golgi staining (dendritic spine), Schiff staining,
HE staining etc.
Immunostaining, confocal microscope-

    Fig. 3. Immunostaining. A and B. NeuN
    staining shows neuronal loss in a knockout
    mouse (B), compared to wild-type mouse (A).
    C and D. GFAP staining in the same mice.
based double/triple immunostaining
(collaboration with local institutes)
Adult neurogenesis;
Dendritic spine/synapse morphology
Subcellular fraction
Fig. 4. Confocal analysis of double immunostaining.
A-F. Double immunostaining of NeuN (red) and
DCX (blue) shows cell proliferation. G-I. Double immunostaining of NeuN (red) and BrdU (green)
shows adult neurogenesis in the dentate gyrus.
Fig. 5. Synaptogenesis/spinogenesis. A-C.
Neurabin-based immunostaining of cerebellar Purkinje’s cell in the mouse. D-G. Golgi impregnation staining of the hippocampus in
the mouse.
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Zhangjiang East Campus, Pudong, Shanghai 201201,
P.R.China
Tel: +86 (21) 5116 3700
Fax: +86 (21) 5116 3766
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