GM1 and the Aged Brain^a

Abstract

Aging is associated with the loss of brain neurotransmitter function, which apparently is the substrate for an adverse constellation of age-associated symptoms. In particular, cholinergic deficits have been associated with cognitive impairment in aging. Systemic administration of GM1 ganglioside, 30 mg/kg, i.p., for 30 days, enhances the cholinergic neurochemical presynaptic markers, choline acetyltransferase, choline uptake, and acetylcholine, in the brain and spinal cord of aged 22-24-month-old Sprague-Dawley rats. In addition to correcting cholinergic neurochemistry, it improves spatial learning and memory impairment, and restores the number and the size of the cholinergic neurons in the basal forebrain and striatum. The induced neuronal recovery by GM1 is long-lasting.

Regulation of axonal development by plasma membrane gangliosides

“…Importantly, these regulatory processes can be spatially confined by local accumulation of ganglioside-converting enzymes, as is the case for PMGS that, from very early neuronal developmental stages, determines the axonal fate (axon vs. dendrites) of a particular young neurite, maintaining the polarization of the neuron later on. There are even good indications of the participation of gangliosides and ganglioside-converting enzymes at the pre-synaptic level in the axons of fully mature neurons (Waki et al 1994;Hadjiconstantinou and Neff 1998;Ando et al 2004), an issue that we did not mention in this review and that deserves to be the object of dedicated discussion.…”

“…There are even good indications of the participation of gangliosides and ganglioside‐converting enzymes at the pre‐synaptic level in the axons of fully mature neurons (Waki et al. 1994; Hadjiconstantinou and Neff 1998; Ando et al. 2004), an issue that we did not mention in this review and that deserves to be the object of dedicated discussion.…”

“…In fact, GM1 added in vitro enhances nerve growth factor (NGF)-induced phosphorylation, dimerization, and activation of Trk receptors (Mutoh et al 1993;Ferrari et al 1995;Mutoh et al 1995;Rabin and Mocchetti 1995;Farooqui et al 1997) as well as brain-derived neurotrophic factor (BDNF)-induced TrkB activation (Pitto et al 1998). These effects are supported by the fact that GM1 enhances NGF effect in vivo (Cuello et al 1989;Fong et al 1995;Hadjiconstantinou and Neff 1998;Panni et al 1998) by enhanced Trk phosphorylation in rat striatum and hippocampus, after intraventricular application of the ganglioside (Duchemin et al 2002).…”

“…1989; Fong et al. 1995; Hadjiconstantinou and Neff 1998; Panni et al. 1998) by enhanced Trk phosphorylation in rat striatum and hippocampus, after intraventricular application of the ganglioside (Duchemin et al.…”

Preferential Regulation of Γ‐Secretase‐Mediated Cleavage of APP by Ganglioside GM1 Reveals a Potential Therapeutic Target for Alzheimer's Disease

“…Intraperitoneal Drug Administration: Mice were intraperitoneally injected with GM1 (30 mg kg −1 ) diluted in saline (0.9%) daily for 28 days. [40][41][42] GM1 was purchased from Qilu Pharmaceutical Co., (Shandong, China). Animals were selected randomly to form different groups: WT CTRL, APP/PS1 CTRL, and APP/PS1 GM1.…”