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Neurology

Introduction

The Neurology unit is especially interested in pathomechanisms involved in neurological and neuromuscular disorders. Movement and muscle function are impaired by several disabling human diseases like ataxias, Parkinson’ s or Huntington´s Disease, Amyotrophic Lateral Sclerosis but are also affected by altered energy metabolism or aging. For characterization of respective mouse models our tests provide an overview on basic neurological functions of mice. To explore the molecular basis for disease on one end, but also to dissect early as well as late disease attributes relevant for human diagnostic and treatment approaches we perform tests for simple neurological function, motor coordination and muscle function, but also assess elementary neuronal function e.g.  in motoneuron diseases.

Screening Pipeline (A)

The primary screening includes a general examination according to a modified SHIRPA protocol (Hatcher et al, 2001), a rapid and semi-quantitative screening method for analysis of abnormal phenotypes in mice by an overall assessment of muscle, motor neuron, spino-cerebellar, sensory and autonomic functions. In addition grip strength and motor coordination (rotarod) is analyzed. Hearing assessment is performed by measuring auditory brainstem responses to different auditory stimuli (ABR).

Hypothesis-driven pipelines

Dependent on primary results and/or additional information about the mouse model more in-depth-analysis can be performed in hypothesis-driven pipelines.

B - Pipeline "Emotionality"

Swim ability - swimming ability

For other tests of this pipeline see Behavior Unit

D - Pipeline “Motor disorders”

Source: Hörterer, GMC
  • Analysis of deficits related to motor and neurodegenerative diseases
  • SHIRPA – primary observation protocol for overall appearance
  • Grip strength – muscle function
  • Rotarod – basic motor coordination and balance
  • Beam Walk - coordination and balance deficits on beams of different diameters
  • Ladder Walk – motor coordination and grasping skills
  • Vertical Pole – integration of motor coordination
  • Inverted grid – muscle strength related to weight bearing
  • Gait analysis – automated analysis of treadmill walking pattern by Digigait (Mousespecifics, Boston, USA)

For other tests of this pipeline see Behavior Unit

 

 

E - Pipeline “Sensory disorders”

  • ABR – auditory function (anesthetized mice)
  • Hotplate – sensitivity to thermal stimuli, integrity of nociceptive pathways
  • Nerve conduction velocities (NCV) – sensory as well as motor neuron functions
  • Seizure susceptibility (PTZ) – lowering seizure threshold by pentetrazole (PTZ) uncovers increased seizure susceptibility
  • Elektroencephalography (EEG) – telemetric surface EEG

For other tests of this pipeline see Behavior and Eye Unit

N - Pipeline “General neuro-behavioural assessment”

  • SHIRPA – primary observation protocol for overall appearance
  • Grip strength – muscle function
  • Rotarod – basic motor coordination and balance
  • ABR – Auditory function (anesthetized mice)
  • Beam Walk - coordination and balance deficits on beams of different diameters
  • Ladder Walk – motor coordination and grasping skills
  • Gait analysis – automated analysis of treadmill walking pattern by Digigait  (Mousespecifics, Boston, USA)

For other tests of this pipeline see Behavior and Eye Unit

Neurological Examination - Primary screen

SHIRPA (Hatcher et al, 2001)

Maus im Becherglas

This primary observation screen is proposed as a rapid and semi-quantitative screening method for analysis of abnormal phenotypes in mice by an overall assessment of muscle, motor neuron, spino-cerebellar, sensory and autonomic functions.

Grip Strength

Grip force is measured to evaluate muscle function of fore paws or all paws.

Rotarod

The performance of mutant mice on the Rotarod provides information about motor coordination and balance as well as basic motor learning skills dependant upon the protocol used.

Auditory Brainstem response (ABR):

The ABR is an electrophysiological recording widely used for determination of hearing sensitivity, e.g. estimation of hearing thresholds for broadband click stimuli and pure tone frequencies.

Secondary Screen (at least 10 animals per sex and genotype needed)

Assessment of ataxia, motor coordination and balance

  • Gait analysis
  • Swim ability
  • Beam walking/ ladder beam
  • Skilled reaching (staircase)
  • Motor skill drums in running wheels; TSE)
  • Electrophysiology: electroneurography (nerve conduction velocities)

Assessment of muscle function

  • Electromyography
  • Nerve conduction studies
  • Running wheel exercise

Assessment of hearing

  • Auditory evoked potentials
  • Auditory Brainstem Response

Assessment of seizure treshold

  • Pentetrazol-induced seizures
  • Telemetric electroencephalography

Additional approaches

  • Challenge with paraquat to induce oxidative stress
  • Application of neuroprotective substances
  • Exercise with running wheels

Head

Dr. Lore Becker
phone: +49 (0)89 3187-2881
lore.becker(at)helmholtz-muenchen.de

Staff

Angelika Badmann
phone: +49 (0)89 3187-4816
angelika.badmann(at)helmholtz-muenchen.de

Expert Partner

Prof. Dr. Thomas Klopstock
Friedrich-Baur-Institut, LMU
Thomas.Klopstock(at)med.uni-muenchen.de