Substance Abuse and Movement Disorders: Complex Interactions and Comorbidities

Deik, Andres; Saunders‐Pullman, Rachel; Luciano, Marta San

doi:10.2174/1874473711205030243

Cited by 66 publications

(68 citation statements)

References 144 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, astrocytes have been previously suggested as important cellular targets in CNS motor disorders [87, 88], although specific molecular targets are not clear. In the context of Meth abuse, movement disorders are very common sequels and comorbidities [89]. On the other hand, the genes upregulated by Meth in astrocytes also suggest a potential acute neuroprotective response.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro

Bortell

Basova

Semenova

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundAstrocyte activation is one of the earliest findings in the brain of methamphetamine (Meth) abusers. Our goal in this study was to identify the characteristics of the astrocytic acute response to the drug, which may be critical in pathogenic outcomes secondary to the use.MethodsWe developed an integrated analysis of gene expression data to study the acute gene changes caused by the direct exposure to Meth treatment of astrocytes in vitro, and to better understand how astrocytes respond, what are the early molecular markers associated with this response. We examined the literature in search of similar changes in gene signatures that are found in central nervous system disorders.ResultsWe identified overexpressed gene networks represented by genes of an inflammatory and immune nature and that are implicated in neuroactive ligand-receptor interactions. The overexpressed networks are linked to molecules that were highly upregulated in astrocytes by all doses of methamphetamine tested and that could play a role in the central nervous system. The strongest overexpressed signatures were the upregulation of MAP2K5, GPR65, and CXCL5, and the gene networks individually associated with these molecules. Pathway analysis revealed that these networks are involved both in neuroprotection and in neuropathology. We have validated several targets associated to these genes.ConclusionsGene signatures for the astrocytic response to Meth were identified among the upregulated gene pool, using an in vitro system. The identified markers may participate in dysfunctions of the central nervous system but could also provide acute protection to the drug exposure. Further in vivo studies are necessary to establish the role of these gene networks in drug abuse pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0825-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro

Bortell

Basova

Semenova

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…However, in contrast to the hyperphosphorylation of tau, our study could not confirm that heroin addiction induces α-synucleinopathy in the examined age-range. Although α-synuclein is highly implicated in Parkinson’s disease, it must be noted that parkinsonian syndromes with encephalopathy after heroin abuse are rare (Deik, et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Heroin abuse exaggerates age-related deposition of hyperphosphorylated tau and p62-positive inclusions

Kovács

Horváth

Majtényi

et al. 2015

Neurobiology of Aging

View full text Add to dashboard Cite

The observation of increased hyperphosphorylated tau levels correlating with microglial activation in opiate abusers has been interpreted as predisposition to accelerated Alzheimer disease (AD)-related changes. The present study focused on evaluating additional neurodegeneration-related proteins, including α-synuclein and TDP-43, and p62-positive deposits. We performed a systematic mapping of protein deposits in the brains of 27 individuals with documented heroin addiction (age: 19-40) and compared with 11 controls (age: 15-40). We confirm previous findings that heroin addiction associates with tau hyperphosphorylation in predilection brain areas for aging and AD. Furthermore, we show that this occurs also in areas implicated in the molecular disturbances and in vivo neuronal networks related to heroin abuse. There was, however, no presence of Amyloid-beta deposits. We extend previous findings by showing the lack of TDP-43 or α-synuclein pathology and emphasize the independent effect of the duration of drug use on the appearance of age-related p62-positive neuritic profiles. These observations provide unique insights about neuropathological alterations in the brains of young heroin addicts and have implications about brain aging and the influences of environmental and toxic factors.

show abstract

“…20,27 Both drug intoxication and drug withdrawal can produce tremor. 28 Seizures can occur in overdose, withdrawal, and with medications at therapeutic doses that lower the seizure threshold. 29 …”

Section: Neurologic Exammentioning

confidence: 99%