Abstract Details

Title Intrathecal delivery of ALS cerebrospinal fluid induces motor deficits and motor neuron death in mice

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-013

Objective

To develop a novel animal model of sporadic amyotrophic lateral sclerosis (ALS), via intrathecal delivery of cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients into mice.

Background ALS is a progressive neurodegenerative disorder characterized by motor neuron death. Only 10% of ALS patients have familial ALS, while the majority are afflicted with sporadic ALS. In most existing genetic rodent models of ALS, an observable disease phenotype takes a relatively long period of time (months) to develop. Here, we investigated whether pathological factors are present in the CSF of the sporadic form of ALS and if this can be studied in an experimental model of the disease.

Design/Methods CSF obtained from ALS patients was administered to mice intrathecally. Control mice were injected with saline, or CSF obtained from healthy individuals, as well as CSF from patients with other neurological disease (OND). Mice underwent a laminectomy at cervical levels 4 and 5, then 3μl of CSF was injected under the dura mater into the subarachnoid space. Forelimb motor deficits were assessed at 1 day post injection, then mice were perfused for histological analyses of the spinal cord.

Results ALS CSF-injected mice exhibited significantly impaired forelimb function compared to controls. Increased death of motor neurons was revealed by a significantly fewer number of ChAT-positive motor neurons and increased activated-caspase3 staining in the cervical spinal cords of ALS CSF-injected mice. Mice injected with ALS CSF displayed evidence of reactive astrogliosis and microglial activation, as assessed by Iba-1 and GFAP immunostaining respectively. These pathological features were not seen in the control groups.

Conclusions Intrathecal delivery of ALS CSF induces motor weakness and degeneration of motor neurons in the cervical spinal cord by 1 day post injection. Identification of the pathological factors present in ALS CSF that are responsible for this degenerative phenotype is an important next step.

Authors/Disclosures
Jamie Wong, PhD (Tisch Multiple Sclerosis Research Center of New York) PRESENTER	Dr. Wong has nothing to disclose.
	No disclosure on file
Serena J. Shimshak, BA (Tisch MS Research Center of New York)	No disclosure on file
Saud Sadiq, BS, FAAN (Tisch Multiple Sclerosis Research Center of New York)	Ms. Brewi has nothing to disclose.

��ɫ��

��ɫ��