CNS Animal Models

WuXi Biology offers a full range of CNS efficacy and safety pharmacology assessments, from basic models and regulatory tests, to the evaluation of abuse and dependence liability and proconvulsant risk using EEG. Our experts provide animal models in all areas of psychopharmacology, cognition, epilepsy and neurodegenerative disorders.


in vivo models for Neurodegenerative Diseases

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
  • Animal Models :
    • APPSWE (Tg2576 (B6:SJL))
    • mice oARTE10 APP PS1 (Model 16437) mice
    • 4XFAD mice oTau P301L JNPL3 (Model 2508) mice
    • APPSWE Tau P301L TAPP (Model 2469)
  • Acute AD-like dementia model
    • Scopolamine
    • Isoflurane
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.

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 models

  • Unilateral intra-striatal injection of 6-OHDA to lesion nigro-striatal dopamine neurons: severe DA neuronal loss, without Lewy body-like inclusion, severe motor dysfunction, but with extensive non-motor symptoms, good response to L-DOPA
  • MPTP-induced PD model in mice: moderate to severe DA neuronal loss, without Lewy body-like inclusion, moderate to severe motor dysfunction and hyperactivity, good response to L-DOPA
  • Systemic administration of MTPT to lesion dopamine neurons in a monkey (under development)

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

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

Stroke Models

  • Middle cerebral artery occlusion (MCAO) model in rats
  • MCAO reperfusion model in rats

Ischemia model

  • Forebrain ischemia model in the gerbil

Psychopharmacology | Mental Disorder Models

By combining experience/expertise from both the pharmaceutical industry and academia, we provide valuable services to accelerate drug discovery for the treatment of psychiatrics diseases and mental disorders.

  • Various stress paradigms including early-life stress (ELS)
  • Multiple approaches from pharmacological, genetic to environmental ones 
  • Studies at the molecular/cellular, histological, and behavior levels

Depression

  • Restraint stress in the mouse
  • Tail suspension in the mouse

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

Schizophrenia/bipolar disorder

  • PCP model in the mouse and rat
  • Sleep-deprivation in the rat

Mental retardation model

  • BDNF knockdown in the mouse


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].

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,
  • social interaction.

Pain-related behavior:

  • hot-plate,
  • tail flick (infrared heat/pressure).

Depression-like behavior:

  • Novelty-induced hypophagia,
  • tail suspension test,
  • forced swim test,
  • open-field behavior,
  • social interaction,
  • 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,
  • nesting behavior.

Drug addictive behavior:

  • Drug-seeking behavior (self-administration; under development),
  • behavioral sensitization,
  • conditioned place preference (CPP),
  • CPP extinction.

Home cage behavior and environmental enrichment.