g(m1)-ganglioside and Atrophy

In this mini-review I summarize our research efforts in ascertaining the possible neuro-reparative properties of the GM1 ganglioside and its cooperative effects with NGF in stroke-lesion models. We also review aspects of our NGF investigations which have recently led to the discovery that NGF is released in an activity-dependent manner in the form of its precursor molecule, proNGF. These studies support the notion that in the CNS NGF metabolism conversion and degradation occur in the extracellular milieu. We have also validated this pathway in vivo demonstrating that the pharmacological inhibition of the pro-to mature NGF conversion results in the brain accumulation of proNGF and loss and atrophy of cortical cholinergic synapses. Furthermore, we have gathered neurochemical evidence for a compromise of this newly discovered NGF metabolic pathway in Alzheimer's disease, explaining the vulnerability of NGF-dependent forebrain cholinergic neurons in this disease despite normal NGF synthesis and abundance of NGF precursor.

Topics: Aging; Animals; Atrophy; Brain; Cholinergic Neurons; G(M1) Ganglioside; Humans; Matrix Metalloproteinase 9; Nerve Growth Factor; Protein Precursors; Stroke; Tissue Plasminogen Activator

The aim of this study was to correlate the brain atrophy with serum levels of anti-GM1 antibodies in patients with relapsing-remitting multiple sclerosis (RRMS).. Plasma sample from 52 patients with RRMS and 65 healthy controls were examined for anti-GM1 antibodies. Patients with RRMS underwent to MRI study with automated method called SIENAX that calculated an estimate of gray matter (GM(V)) and white matter (WM(V)) volumes.. The percentage of RRMS patients with increased anti-GM1 was 37.8%. Elevated levels of anti-GM1 antibodies did not correlate with brain atrophy.. Anti-GM1 antibodies do not represent a marker of axonal damage in patients with RRMS.

Topics: Adolescent; Adult; Atrophy; Autoantibodies; Biomarkers; Brain; G(M1) Ganglioside; Humans; Multiple Sclerosis, Relapsing-Remitting; Young Adult

Multifocal motor neuropathy (MMN) with conduction block is an acquired, autoimmune-mediated neuropathy that is responsive to treatment. The clinical history is one of slowly, progressive distal weakness, which more commonly involves the upper extremities, and it affects mainly young adults. Physical examination reveals weakness without sensory loss in the distribution of individual nerves. Atrophy may be present, but hyperreflexia and spasticity are not seen. Electrophysiological studies reveal motor conduction blocks at sites not prone to compression with normal sensory responses. Immunoglobulin M anti-GM1 titers may be elevated. Treatment with human immunoglobulin or cyclophosphamide has been shown to improve strength in the majority of patients with MMN in the short term. However, motor strength and function may gradually decline over years in spite of long-term therapy.

Topics: Adult; Atrophy; Autoimmune Diseases; Cyclophosphamide; Diagnosis, Differential; Electrophysiology; G(M1) Ganglioside; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Motor Neuron Disease; Neural Conduction; Peripheral Nervous System Diseases; Prognosis

The rubrospinal tract (RST) was cut unilaterally at C2-3 segment in 21 rats that were killed 3, 7, 10, 14, 28, 60, and 90 days later. Additionally, 14 rats, killed 14 or 28 days after lesioning, were treated postoperatively by daily intraperitoneal injections of GM1 ganglioside. Six unoperated, untreated rats served as controls. In untreated animals, axotomized neurons of the magnocellular division of the red nucleus (RN) exhibited cytoplasmic, nuclear, and nucleolar atrophy 7-10 days postoperatively. Atrophy progressed through the 90th postoperative day. Regression analyses disclosed a bimodal pattern to cytoplasmic and nucleolar atrophy, with an initial rapid phase changing to a slower but progressive mode from 14 days postoperatively. Nuclear atrophy proceeded in a unimodal manner. GM1 treatment did not affect these atrophic processes. Neuronal loss did not occur in the axotomized RN through the 60th postoperative day. Axotomized neurons of untreated rats showed significant and progressive reductions in mean somal (cytoplasmic) and nucleolar RNA from, respectively, the 7th and 14th postoperative day. GM1 partly prevented these RNA losses. Both in treated and untreated rats, spinal cord lesions contained many axonal sprouts 2 to 4 weeks after surgery, but newly generated axons did not traverse the rostro-caudal extent of any lesion.

Topics: Animals; Atrophy; Female; G(M1) Ganglioside; Nerve Degeneration; Rats; Rats, Inbred Strains; Red Nucleus; RNA; Spinal Cord; Time Factors

The clinical and pathological manifestations of a case of juvenile GM1 gangliosidosis are presented and the pathological findings compared with those previously reported for GM1 gangliosidosis in man and in animal models. The most striking finding in the present case was the marked degeneration of the retinal ganglion cell and nerve fiber layers. Although such extensive ganglion cell loss was not observed in any of the other cases reviewed, the presence of multimembranous inclusion bodies in retinal ganglion cells strongly suggests that the pathological process was similar in all cases. Much remains to be learned about the function of gangliosides in the healthy retina and about the pathophysiological consequences of deranged ganglioside metabolism. The many parallels, including those observed in pathological studies, between the human and animal forms of GM1 gangliosidosis allow an optimistic appraisal of the value of further research using the animal models.

Topics: Animals; Atrophy; Cats; Cattle; Conjunctiva; Cornea; Disease Models, Animal; Dogs; Epithelium; Eye; Eye Diseases; Female; G(M1) Ganglioside; Gangliosidoses; Humans; Infant; Retina; Retinal Ganglion Cells