Autophagy as a gateway for the effects of methamphetamine: From neurotransmitter release and synaptic plasticity to psychiatric and neurodegenerative disorders

Limanaqi, Fiona; Busceti, Carla Letizia; Celli, Roberta; Biagioni, Francesca; Fornai, Francesco

doi:10.1016/j.pneurobio.2021.102112

Cited by 21 publications

(15 citation statements)

References 334 publications

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“…Methamphetamine (METH) is a psychostimulant that is neurotoxic for monoamine neurons and most dopamine (DA)-containing neurons [ 1 , 2 , 3 , 4 , 5 ]. The selective toxicity of METH is based on the selective uptake by presynaptic transporters, namely the DA transporter (DAT) [ 6 ], norepinephrine transporter (NET) and serotonin transporter (SERT) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Alterations of Mitochondrial Structure in Methamphetamine Toxicity

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Biagioni

Busceti

et al. 2022

IJMS

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Recent evidence shows that methamphetamine (METH) produces mitochondrial alterations that contribute to neurotoxicity. Nonetheless, most of these studies focus on mitochondrial activity, whereas mitochondrial morphology remains poorly investigated. In fact, morphological evidence about the fine structure of mitochondria during METH toxicity is not available. Thus, in the present study we analyzed dose-dependent mitochondrial structural alterations during METH exposure. Light and transmission electron microscopy were used, along with ultrastructural stoichiometry of catecholamine cells following various doses of METH. In the first part of the study cell death and cell degeneration were assessed and they were correlated with mitochondrial alterations observed using light microscopy. In the second part of the study, ultrastructural evidence of specific mitochondrial alterations of crests, inner and outer membranes and matrix were quantified, along with in situ alterations of mitochondrial proteins. Neurodegeneration induced by METH correlates significantly with specific mitochondrial damage, which allows definition of a scoring system for mitochondrial integrity. In turn, mitochondrial alterations are concomitant with a decrease in fission/mitophagy protein Fis1 and DRP1 and an increase in Pink1 and Parkin in situ, at the mitochondrial level. These findings provide structural evidence that mitochondria represent both direct and indirect targets of METH-induced toxicity

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Section: Introductionmentioning

confidence: 99%

Alterations of Mitochondrial Structure in Methamphetamine Toxicity

Lenzi

Biagioni

Busceti

et al. 2022

IJMS

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“…These evidence suggest that Rapa rescues the defects of autophagy induced by Meth in neurons. Therefore, the enhanced clearance of A β and p-tau may be ascribed to the restore of autophagic flux [ 37 ], which confirms the critical roles of autophagy in A β and p-tau clearance. Noteworthily, it is known the importance of the inflammatory cells on the pathological AD proteins' clearance, especially the microglia [ 32 ].…”

Section: Discussionmentioning

confidence: 83%

Targeting Aβ and p-Tau Clearance in Methamphetamine-Induced Alzheimer’s Disease-Like Pathology: Roles of Syntaxin 17 in Autophagic Degradation in Primary Hippocampal Neurons

Zhu

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Methamphetamine (Meth), a central nervous system (CNS) stimulant with strong neurotoxicity, causes progressive cognitive impairment with characterized neurodegenerative changes. However, the mechanism underlying Meth-induced pathological changes remains poorly understood. In the current study, Meth elicited a striking accumulation of the pathological proteins hyperphosphorylated tau (p-tau) and amyloid beta (Aβ) in primary hippocampal neurons, while the activation of autophagy dramatically ameliorated the high levels of these pathological proteins. Interestingly, after the Meth treatment, Aβ was massively deposited in autophagosomes, which were remarkably trapped in early endosomes. Mechanistically, syntaxin 17 (Stx17), a key soluble n-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) protein responsible for autophagosome and mature endosome/lysosome fusion, was significantly downregulated and hindered in combination with autophagosomes. Notably, adenovirus overexpression of Stx17 in primary neurons facilitated autophagosome-mature endosome/lysosome fusion, which dramatically reversed the Meth-induced increases in the levels of p-tau, Aβ, beta-secretase (Bace-1), and C-terminal fragments (CTFs). Immunofluorescence assays showed that Stx17 retarded the Meth-induced Aβ, p-tau, and Bace-1 accumulation in autophagosomes and facilitated the translocation of these pathological proteins to lysosomes, which indicated the importance of Stx17 via enhanced autophagosome-mature endosome/lysosome fusion. Therefore, the current study reveals a novel mechanism involving Meth-induced high levels of pathological proteins in neurons. Targeting Stx17 may provide a novel therapeutic strategy for Meth-induced neurodegenerative changes.

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“…As previously mentioned, the expression of BDNF can promote the survival of neurons (Wang et al, 2020b), suggesting that synaptic plasticity is related to the survival of neurons (Labandeira et al, 2021;Limanaqi et al, 2021). Meanwhile, previous studies have shown that anesthesia and surgery caused PND by triggering microglia activation and neuron loss (Zhang et al, 2016).…”

Section: Discussionmentioning

confidence: 94%

“…Synaptic plasticity is related to the neuronal survival (Labandeira et al, 2021;Limanaqi et al, 2021). Neuronal loss is also one of the main pathological mechanisms of PND (Zhang et al, 2016).…”

Section: Clemastine Prevented the Loss Of Hippocampal Mature Neurons In Aged Mice With Perioperative Neurocognitive Disordermentioning

confidence: 99%

Clemastine Ameliorates Perioperative Neurocognitive Disorder in Aged Mice Caused by Anesthesia and Surgery

Zhang

Zhou

et al. 2021

Front. Pharmacol.

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Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.

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Autophagy as a gateway for the effects of methamphetamine: From neurotransmitter release and synaptic plasticity to psychiatric and neurodegenerative disorders

Cited by 21 publications

References 334 publications

Alterations of Mitochondrial Structure in Methamphetamine Toxicity

Alterations of Mitochondrial Structure in Methamphetamine Toxicity

Targeting Aβ and p-Tau Clearance in Methamphetamine-Induced Alzheimer’s Disease-Like Pathology: Roles of Syntaxin 17 in Autophagic Degradation in Primary Hippocampal Neurons

Clemastine Ameliorates Perioperative Neurocognitive Disorder in Aged Mice Caused by Anesthesia and Surgery

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