Quantitative activation-induced manganese-enhanced MRI reveals severity of Parkinson’s disease in mice

Abstract

We demonstrate that activation-induced manganese-enhanced magnetic resonance imaging with quantitative determination of the longitudinal relaxation time (qAIM-MRI) reveals the severity of Parkinson’s disease (PD) in mice. We first show that manganese ion-accumulation depends on neuronal activity. A highly active region was then observed by qAIM-MRI in the caudate-putamen in PD-model mice that was significantly correlated to the severity of PD, suggesting its involvement in the expression of PD symptoms.

Ceftriaxone Treatment for Neuronal Deficits: A Histological and MEMRI Study in a Rat Model of Dementia with Lewy Bodies

“…with MnCl 2 , and its neurons took up Mn 2+ when activated. A quantitative analysis indicated that Mn 2+ accumulates in neurons according to their activity, because Ca 2+ elevation is related to the firing activity in excitatory neurons [ 23 ]. In addition, its paramagnetic feature enables Mn 2+ to shorten the longitudinal relaxation time (T1) of water protons and thus enhance the T1-weighted MR signal that is specific to the tissues where Mn 2+ has accumulated [ 24 ], thus rendering it an excellent MRI-detectable contrast agent [ 25 ].…”

Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases

“…Quantitative AIM-MRI uses a quantitative T1 value (or R1 value = T1 −1 ) to quantify the neuronal activity map of the entire brain, revealing the patterns and locations of changes in neuronal activity in animal models of PD. In particular, a quantitative analysis of the R1 value in the dorsal caudate-putamen determines the severity of PD and thus facilitates proper treatment (117). Unilateral SNc injury in the rat model of 6-hydroxydopamine (OHDA)-induced PD causes bilateral changes, and the T2 relaxation time of the bilateral SNc increases on MRI.…”

Store-Operated Calcium Channels Are Involved in Spontaneous Slow Calcium Oscillations in Striatal Neurons

“…The methods for Ca 2+ imaging were described previously (Osanai et al, 2006;Tamura et al, 2014;Kikuta et al, 2015). Briefly, postnatal day 12 (P12) to P17 GAD67-GFP mice of either sex were anesthetized with isoflurane (Mylan) and decapitated.…”

“…As previously described (Kikuta et al, 2015), [Ca 2+ ] i elevation and manganese ion (Mn 2+ ) quenching was measured in striatal cells loaded with the ratiometric Ca 2+ sensitive dye Fura-2 LR/AM. The dye-loading methods used were as previously described (Osanai et al, 2006;Tamura et al, 2014).…”

“…Mn 2+ can pass through opened Ca 2+ -permeable channels and quenches the Fura-2 LR fluorescence emission (Amano et al, 1997;Kikuta et al, 2015). Thus, to evaluate Ca 2+ influx from the extracellular space, the rate of the quench by Mn 2+ was quantified as ∆ F/F at 380 nm (Uehara et al, 2002;Tu et al, 2009;Kikuta et al, 2015). To evaluate the influx rate of Mn 2+ , the time constant of quenching (τ q ) after MnCl 2 perfusion was calculated by fitting with the following equation:…”