Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis.
OBJECTIVE
Recent data in mouse and rat demyelination models indicate that administration of thyroid hormone (TH) has a positive effect on the demyelination/remyelination balance. As axonal pathology has been recognized as an early neuropathological event in multiple sclerosis, and remyelination is considered a pre-eminent neuroprotective strategy, in this study we investigated whether TH administration improves nerve impulse propagation and protects axons.


METHODS
We followed up the somatosensory evoked potentials (SEPs) in triiodothyronine (T3)-treated and untreated experimental allergic encephalomyelitis (EAE) Dark-Agouti female rats during the electrical stimulation of the tail nerve. T3 treatment started on the 10th day post immunization (DPI) and a pulse administration was continued until the end of the study (33 DPI). SEPs were recorded at baseline (8 DPI) and the day after each hormone/ vehicle administration.


RESULTS
T3 treatment was associated with better outcome of clinical and neurophysiological parameters. SEPs latencies of the two groups behaved differently, being briefer and closer to control values (=faster impulse propagation) in T3-treated animals. The effect was evident on 24 DPI. In the same groups of animals, we also investigated axonal proteins, showing that T3 administration normalizes neurofilament immunoreactivity in the fasciculus gracilis and tau hyperphosphorylation in the lumbar spinal cord of EAE animals. No sign of plasma hyperthyroidism was found; moreover, the dysregulation of TH nuclear receptor expression observed in the spinal cord of EAE animals was corrected by T3 treatment.


CONCLUSIONS
T3 supplementation results in myelin sheath protection, nerve conduction preservation and axon protection in this animal model of multiple sclerosis.
Department of Neurology, University Campus Bio-Medico, Rome, Italy.
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ML
Dell'Acqua
L
L
Lorenzini
G
G
D'Intino
S
S
Sivilia
P
P
Pasqualetti
V
V
Panetta
M
M
Paradisi
M M
MM
Filippi
C
C
Baiguera
M
M
Pizzi
L
L
Giardino
P M
PM
Rossini
L
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Calzà
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013963:Thyroid Hormones / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000627:therapeutic use
D018696:Neuroprotective Agents; D013963:Thyroid Hormones; D014284:Triiodothyronine