Bee Venom and Its Component Apamin as Neuroprotective Agents in a Parkinson Disease Mouse Model

Abstract

Bee venom has recently been suggested to possess beneficial effects in the treatment of Parkinson disease (PD). For instance, it has been observed that bilateral acupoint stimulation of lower hind limbs with bee venom was protective in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In particular, a specific component of bee venom, apamin, has previously been shown to have protective effects on dopaminergic neurons in vitro. However, no information regarding a potential protective action of apamin in animal models of PD is available to date. The specific goals of the present study were to (i) establish that the protective effect of bee venom for dopaminergic neurons is not restricted to acupoint stimulation, but can also be observed using a more conventional mode of administration and to (ii) demonstrate that apamin can mimic the protective effects of a bee venom treatment on dopaminergic neurons. Using the chronic mouse model of MPTP/probenecid, we show that bee venom provides sustained protection in an animal model that mimics the chronic degenerative process of PD. Apamin, however, reproduced these protective effects only partially, suggesting that other components of bee venom enhance the protective action of the peptide.

Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis

“…In addition, BV was reported to directly inhibit apoptosis in SH-SY5Y human neuroblastoma cells (Doo et al, 2012). Furthermore, previous studies reported direct neuroprotective effect of BV on MPP + or MPTP/probenecid-induced apoptotic cell death (Alvarez-Fischer et al, 2013;Doo et al, 2012) supporting the current observation. Fig.…”

“…Apamin, through acting on Ca 2+ -activated K + (SK) channels, reserved dopaminergic neurons in MPTP/ probenecid-intoxicated mice (Alvarez-Fischer et al, 2013) and elevated dopamine level in prefrontal cortex of rats (Steketee and Kalivas, 1990). Mellitin, the major component of BV, inhibits the activity of Na/K-ATPase pump (Yang and Carrasquer, 1997) that adds protection to dopaminergic neurons in vitro (Salthun-Lassalle et al, 2004).…”

“…Based on these previous observations, the current protective effect of BVA can be justified. However, Alvarez-Fischer et al (2013) reported that BV produces neuroprotection independently from the anti-inflammatory properties. Indeed, oxidative damage plays a central role in the pathogenesis of PD as proven in human and animal studies (Sian et al, 1994).…”

Neuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease

“…This explains why antimitotic agents such as cytarabine, which interfere directly with glial mechanisms and compounds, which stimulate neuronal excitability such as nicotine and the bee venom component apamin, were reported to provide substantial protection in this paradigm [22,35]. Of interest, nicotine and apamin were also protective in animal models of the disease, which attests to the validity of this culture system and reinforce the interest of the present results obtained with MPAQ [36,37]. Another related molecule, 5b promoted exclusively differentiation.…”

From Intrinsic Firing Properties to Selective Neuronal Vulnerability in Neurodegenerative Diseases

“…The resulting silencing of vulnerable neurons involves both burst and pacemaking firing and precedes neuronal degeneration (Good et al, 2011;Michel et al, 2013). Consistent with the existence of a causal relationship between hyperpolarization and degeneration, inhibition of slow potassium conductances or activation of sodium channels in vulnerable neurons is neuroprotective against genetic and toxic insults (Salthun-Lassalle et al, 2004;Chan et al, 2007;Alvarez-Fischer et al, 2013). Greatly reduced firing before degeneration might account for the poor correlation between dysfunction and neuronal losses in PD.…”