Proximal sciatic axotomy does not inhibit the induction of neurofilamentous inclusions following intracisternal aluminum chloride exposure.
We have previously demonstrated an acute, dose-dependent suppression of low molecular weight neurofilaments (NFL) and intermediate molecular weight neurofilaments (NFM) steady state mRNA levels while sparing those of high molecular weight (NFH) mRNA 48 hours (h) following the intracisternal inoculation of AlCl3 in young adult New Zealand white rabbits. To determine whether this alteration in NF steady state mRNA stoichiometry is a necessary prerequisite to the induction of neurofilamentous inclusions, we examined the response of spinal motor neurons to aluminum exposure in vivo following axotomy. Forty-eight h following a complete transection of the proximal sciatic nerve, rabbits were inoculated intracisternally with either 1000 microg AlCl3 in 100 microl 0.9% NaCl or 0.9% NaCl alone. Rabbits were killed at either 48 or 120 h post-inoculation, and the extent of neurofilamentous inclusion formation quantified in both the cervical and the lumbosacral cord. Following the axotomy, rabbits developed an ipsilateral hind-limb paralysis. In spinal motor neurons ipsilateral to the axotomy, chromatolytic changes were observed and both NFH and NFM mRNA levels were significantly reduced (p<0.001). At 48 h post-AlCl3 inoculation, 29% of motor neurons contralateral to the axotomy demonstrated inclusions, whereas 43% of ipsilateral motor neurons demonstrated inclusions (Fisher's test, two tailed, p = 0.0196). At 120 h post-axotomy 75% and 83%, respectively, of neurons were involved (p = 0.0212). Neurofilamentous inclusions did not form in NaCl-inoculated rabbits. These observations indicate that an altered stoichiometry of NF mRNA steady levels, with a relative overexpression of NFH mRNA, is not critical to the induction of neurofilamentous inclusions following AlCl3 exposure.
Strong
M J
MJ
John P. Robart Research Institute, University of Western Ontario, London, Ontario, Canada.
Gaytan-Garcia
S
S
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D017403:In Situ Hybridization; D009046:Motor Neurons / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012584:Sciatic Nerve / Q000187:drug effects*; D013997:Time Factors
D017607:Aluminum Compounds; D002712:Chlorides; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D000077410:Aluminum Chloride