Animal models of early-stage Parkinson’s disease and acute dopamine deficiency to study compensatory neurodegenerative mechanisms

Grandi, Laura Clara; Giovanni, Giuseppe Di; Galati, Salvatore

doi:10.1016/j.jneumeth.2018.08.012

Cited by 30 publications

(36 citation statements)

References 177 publications

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“…In the present study, we demonstrated that the TTX-inhibition of the medial forebrain bundle (MFB) (for technical details, see our review [27]) determined an acute increase in GABA content with the reduction of the MTh activity. In rats, the SNr activity is reduced after acute DA depletion caused by TTX [36], in accordance with electrophysiological and biochemical data obtained in PD patients [37].…”

Section: Discussionmentioning

confidence: 64%

“…Another limitation of this study is the use of toxin-induced PD animal models and anesthetized preparations. Despite the usefulness of the animal models, they have limitations that need to be considered when interpreting our findings and translating them to humans [27]. Nevertheless, although rodent models cannot recapitulate all features of PD, they remain a crucial approximation in order to open new avenues.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacological blockade of the MFB was performed on adult male Sprague-Dawley rats weighing 399 ± 68.4 g according to our previously described method [6,27]. Briefly, TTX was infused via reverse microdialysis using a probe with a 1 mm dialytic membrane (CMA/11 microdialysis probe, CMA Microdialysis, Stockholm, Sweden), which was positioned according to the following coordinates: 2.5 mm posterior to the bregma, 2 mm lateral to the midline and 8.6 mm below the cortical surface [43].…”

Section: Pharmacological Blockade Of the Medial Forebrain Bundlementioning

confidence: 99%

“…We performed standard unilateral 6-OHDA denervation in the left hemisphere [6,27] to obtain chronic DA-depleted animals. The animals (399 ± 36.3 g) were anesthetized with 1.5%-2.5% isoflurane in oxygen and then injected with desipramine (25 mg/kg, i.p.)…”

Section: Unilateral 6-ohda Lesionmentioning

confidence: 99%

“…Rats were anesthetized with urethane (1.4 g/kg, i.p.) (Sigma Chemical Co., St Louis, MO, USA) and mounted on a stereotaxic instrument (Stoelting Co.) according to our standard operating procedure [6,27]. Body temperature was maintained at 37-38 • C with a heating pad (Stoelting Co.).…”

Section: Prerecording Surgerymentioning

confidence: 99%

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Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Giovanni

Grandi

Fedele

et al. 2020

IJMS

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The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state.Int. J. Mol. Sci. 2020, 21, 2734 2 of 13 particular, the MTh receives the BG input at the level of the ventral-anterior (VA) and the ventral-medial (VM) nuclei [2]. BG are assumed to inhibit the thalamus under basal conditions because substantia nigra pars reticulata (SNr) and internal globus pallidus (GPi) display high spontaneous spiking rates, releasing GABA in the MTh. However, when the BG network is activated by cortical input, BG output is transiently suppressed and downstream targets, including the MTh, are disinhibited [3,4]. Another source of GABA in the MTh comes from the nucleus reticular thalami (NRT) [5], a thin layer of GABAergic cells adjacent to the relay nuclei of the dorsal thalamus, that we have shown to be able to modulate the oscillatory activity of MTh in dopamine (DA)-depleted animals [6]. On the other hand, the excitatory input to the MTh is classically provided by the cerebellothalamic [7] and corticothalamic synapses [8,9]. Moreover, it has been recently shown that some substantia nigra (SN) neurons project to the NRT and the posterior thalamus, and co-release glutamate (GLU) and DA, while the VA and VM would receive preferential GABAergic SN fibers [10]. GABA, GLU and DA, therefore, may interact when modulating synapse and excitability within the MTh in normal and pathological conditions [11][12][13][14]. Although it is well established that the appearance of the cardinal features of Parkinson's disease (PD) is due to the degeneration of...

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Blockade Of the Medial Forebrain Bundlementioning

confidence: 99%

Section: Unilateral 6-ohda Lesionmentioning

confidence: 99%

Section: Prerecording Surgerymentioning

confidence: 99%

See 3 more Smart Citations

Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Giovanni

Grandi

Fedele

et al. 2020

IJMS

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Individual‐specific metabolic network based on ¹⁸F‐FDG PET revealing multi‐level aberrant metabolisms in Parkinson's disease

Lu,

Song,

et al. 2024

Human Brain Mapping

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Metabolic network analysis in Parkinson's disease (PD) based on 18F‐FDG PET has revealed PD‐related metabolic patterns. However, alterations at the systemic metabolic network level and at the connection level between different brain regions still remain unknown. This study aimed to explore metabolic network alterations at multiple network levels among PD patients using an individual‐specific metabolic network (ISMN) approach. 18F‐FDG‐PET images of patients with PD (n = 34) and healthy subjects (n = 47) were collected. Healthy subjects were further separated into reference group (n = 28) and control group (n = 19) randomly. Standardized uptake value normalized by lean body mass ratio (SULr) maps was calculated from the PET images. ISMNs were constructed based on SULr maps for PD patients and controls with reference to the reference group. Comparisons of nodal and edge features were performed between PD and control groups. Correlation analysis was conducted between multilevel network properties and clinical scales in PD group. A linear classifier was trained based on nodal or edge features to distinguish PD from controls. The distance from each patient's ISMN to the group‐level difference network showed a negative correlation with Hoehn and Yahr stage (r = −0.390, p = .023). Eight nodes from ISMN were identified which exhibited significantly increased nodal degree in PD patients compared to controls (p < .05). Eleven edges were observed which demonstrated significant distinctions in Z‐score values in comparisons to the control group (p < .05). Furthermore, the nodal and edge features showed comparable performances in PD diagnosis compared to the traditional SULr values, with area under the receiver operating characteristic curve larger than 0.91. The proposed ISMN approach revealed systemic metabolic deviations, as well as nodal and edge distinctions in PD, which might be supplementary to the existing findings on PD‐related metabolic patterns.

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Preservation of Dopamine Levels in a Mouse Model of Parkinson's Disease by Carboxymethylated Silica and Starch Nanoparticles Coupled to Silybin

et al. 2023

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Silybin has a neuroprotective effect in different models of neurodegenerative diseases as the MPTP‐induced parkinsonian model. However, silybin has poor water solubility, decreasing its efficacy when administered orally. Therefore, the search for possible vehicles or transport systems is relevant. Among the options are the drug delivery systems (DDS). In this work, we evaluated if the use of specific solvents (water or oil) or DDS [carboxymethylated silica nanoparticles (SiO2_SIL) or starch (CMS‐SIL)] would preserve the neuroprotective effect of silybin when administered orally in a Parkinson's model induced with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). C57BL/6J male mice were exposed to MPTP (30 mg/kg i.p) and, 30 minutes after, were treated with 100 mg/kg of silybin in oil or water as solvents or coupled to silica nanoparticles or carboxymethyl starch for five consecutive days. After the last administration of MPTP and silybin, striatal dopamine levels were determined on day seven. Our results showed that silybin in water as the non‐vehicle control had no protective effect in the MPTP model. Silybin in oil preserved 57 % dopamine levels in contrast to 72 % with SiO2_SIL and 50.7 % with CSM‐SIL. In conclusion, we demonstrated that silybin was effectively coupled to carboxymethylated silica nanoparticles and carboxymethylated starch‐based DDS without losing its neuroprotective effects.

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Animal models of early-stage Parkinson’s disease and acute dopamine deficiency to study compensatory neurodegenerative mechanisms

Cited by 30 publications

References 177 publications

Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Individual‐specific metabolic network based on ¹⁸F‐FDG PET revealing multi‐level aberrant metabolisms in Parkinson's disease

Preservation of Dopamine Levels in a Mouse Model of Parkinson's Disease by Carboxymethylated Silica and Starch Nanoparticles Coupled to Silybin

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Animal models of early-stage Parkinson’s disease and acute dopamine deficiency to study compensatory neurodegenerative mechanisms

Cited by 30 publications

References 177 publications

Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Individual‐specific metabolic network based on 18F‐FDG PET revealing multi‐level aberrant metabolisms in Parkinson's disease

Preservation of Dopamine Levels in a Mouse Model of Parkinson's Disease by Carboxymethylated Silica and Starch Nanoparticles Coupled to Silybin

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Individual‐specific metabolic network based on ¹⁸F‐FDG PET revealing multi‐level aberrant metabolisms in Parkinson's disease