ABSTRACT
In mouse models of familial amyotrophic lateral sclerosis (fALS), motor neurons are especially vulnerable to oxidative stresses in vitro. To determine whether this increased vulnerability also extends to motor nerve terminals in vivo, we assayed the effect of tourniquet-induced ischemia/reperfusion (I/R) injury on motor terminals innervating fast and slow hindlimb muscles in male G93A-SOD1 mice and their wild-type littermates. These mice also expressed yellow fluorescent protein (YFP) in motor neurons. We report that in SOD1-G93A/YFP mice the motor terminals innervating two predominantly fast muscles, extensor digitorum longus (EDL) and plantaris, were more vulnerable to I/R injury than motor terminals innervating the predominantly slow soleus muscle. The mean duration of EDL ischemia required to produce a 50% reduction in endplate innervation in SOD1-G93A/YFP mice was 26 min, compared to 45 min in YFP-only mice. The post-I/R destruction of EDL terminals in SOD1-G93A mice was rapid (<2 h) and was not duplicated by cutting the sciatic nerve at the tourniquet site. The increased sensitivity to I/R injury was evident in EDL muscles of SOD1-G93A/YFP mice as young as 31 days, well before the onset of motor neuron death at approximately 90 days. This early vulnerability to I/R injury may correlate with the finding (confirmed here) that in fALS mice motor nerve terminals innervating fast hindlimb muscles degenerate before those innervating slow muscles, at ages that precede motor neuron death. Early vulnerability of fast motor terminals to I/R injury thus may signal, and possibly contribute to, early events involved in motor neuron death.
Subject(s)
Genetic Predisposition to Disease , Muscle Fibers, Fast-Twitch , Muscle, Skeletal/innervation , Mutation , Nerve Endings/blood supply , Reperfusion Injury/genetics , Superoxide Dismutase/genetics , Adenine , Animals , Denervation , Guanine , Hindlimb , Humans , Male , Mice , Mice, Transgenic , Motor Endplate/physiopathology , Muscle Fibers, Slow-Twitch , Nerve Regeneration , Reperfusion Injury/physiopathology , Superoxide Dismutase-1ABSTRACT
The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation both in the connective tissue and around blood vessels, which includes nociceptive axons and their terminals; these display intense calcitonin gene-related peptide (CGRP) immunoreactivity. Stereotactic electrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, caused marked increase and disintegration of club-like perivascular CGRP-immunopositive nerve endings in the dura mater and induced an apparent increase in the lengths of CGRP-immunoreactive axons. Intravenous administration of sumatriptan or eletriptan, prior to electrical stimulation, prevented disintegration of perivascular terminals and induced accumulation of CGRP in terminal and preterminal portions of peripheral sensory axons. Consequently, immunopositive terminals and varicosities increased in size; accumulation of axoplasmic organelles resulted in the "hollow" appearence of numerous varicosities. Since triptans exert their anti-migraine effect by virtue of agonist action on 5-HT(1D/B) receptors, we suggest that these drugs prevent the release of CGRP from perivascular nerve terminals in the dura mater by an action at 5-HT(1D/B) receptors. Nitroglycerine (NitroPOHL), given subcutaneously to rats, induces increased beading of nitric oxide synthase (NOS)-immunoreactive nerve fibers in the supratentorial cerebral dura mater, and an apparent increase in the number of NOS-immunoreactive nerve fibers in the dural areas supplied by the anterior and middle meningeal arteries, and the sinus sagittalis superior. Structural alterations of nitroxidergic axons innervating blood vessels of the dura mater support the idea that nitric oxide (NO) is involved in the induction of headache, a well-known side effect of coronary dilator agents.
Subject(s)
Dura Mater/metabolism , Migraine Disorders/metabolism , Nerve Fibers/metabolism , Neuropeptides/metabolism , Nitric Oxide Synthase/metabolism , Animals , Capillaries/innervation , Capillaries/ultrastructure , Dura Mater/blood supply , Dura Mater/ultrastructure , Electric Stimulation , Female , Immunohistochemistry , Indoles/pharmacology , Male , Microscopy, Electron , Nerve Endings/blood supply , Nerve Endings/physiopathology , Nerve Fibers/drug effects , Nerve Fibers/ultrastructure , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitroglycerin/pharmacology , Pyrrolidines/pharmacology , Rats , Rats, Wistar , Serotonin Receptor Agonists/pharmacology , Sumatriptan/pharmacology , Trigeminal Ganglion/physiopathology , Trigeminal Ganglion/ultrastructure , Tryptamines , Vasoconstrictor Agents/pharmacologyABSTRACT
It could be proved that the typ I/2-cells are the preferred capillarized nerve cells not only in the plexus Schabadasch (Stach 1977a), but also in the plexus Auerbach. It underlines the special importance of this type of cells for the function of the nervous system of the intestinal wall. Our findings concerning the vascularisation of the intramural nerve plexuses allow to conclude that the regular blood-supply is decisively important for a normal function of the nervous system of the intestinal wall. The knowledge of these facts might be of interest for gastroenterology.
