scholarly journals Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson’s disease

Brain ◽  
2012 ◽  
Vol 135 (6) ◽  
pp. 1884-1899 ◽  
Author(s):  
Cinzia Costa ◽  
Carmelo Sgobio ◽  
Sabrina Siliquini ◽  
Alessandro Tozzi ◽  
Michela Tantucci ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Long Term Potentiation ◽  
Term Potentiation

Impaired long-term potentiation–like plasticity of the trigeminal blink reflex circuit in Parkinson's disease

2006 ◽  
Vol 21 (12) ◽  
pp. 2230-2233 ◽  
Author(s):  
Fortunato Battaglia ◽  
Maria Felice Ghilardi ◽  
Angelo Quartarone ◽  
Sergio Bagnato ◽  
Paolo Girlanda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Long Term Potentiation ◽  
Blink Reflex ◽  
Term Potentiation

25. The LRRK2-R1441C mutation disrupts long-term potentiation-like plasticity in Parkinson’s disease patients

2017 ◽  
Vol 128 (12) ◽  
pp. e421
Author(s):  
R. Dubbioso ◽  
A. De Rosa ◽  
M. Esposito ◽  
S. Peluso ◽  
R. Iodice ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Repositioning Doxycycline for treating Parkinson’s Disease: evidence from a pre-clinical mouse model

2022 ◽  
Author(s):  
Pietro La Vitola ◽  
Luisa Artioli ◽  
Milica Cerovic ◽  
Cristian Poletto ◽  
Letizia Dacomo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Motor Impairment ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Cognitive Behaviour ◽  
Effect Of Treatment ◽  
First Time

Abstract Background Parkinson’s disease remains orphan of valuable therapies capable to interfere with the disease pathogenesis despite the large number of symptomatic approaches adopted in clinical practice to manage this disease. Treatments simultaneously affecting α-synuclein (α-syn) oligomerization and neuroinflammation may counteract Parkinson’s disease. Recent data demonstrated that Doxycycline an antibiotic of the tetracycline class, can inhibit α-syn aggregation and exert anti-inflammatory activity. We herein investigate, for the first time, the potential therapeutic properties of Doxy in a human α-syn A53T transgenic Parkinson’s disease mouse model by the evaluation of behavioural, biochemical and histopathological parameters. Methods human α-syn A53T transgenic mice were treated with Doxycycline (10 mg/Kg daily ip) for 30 days, the effect of treatment on motor and cognitive behaviour impairment and daily live activity of mice were examined, successively immunocytochemical, electrophysiological and biochemical analysis of cerebral tissue was performed. Results Doxy treatment abolished cognitive and daily life activity deficiencies in A53T mice. The effect on cognitive functions was associated with neuroprotection, inhibition of α-syn oligomerization and gliosis both in the cortex and hippocampus. Doxy treatment restored hippocampal long-term potentiation in association with inhibition of pro-inflammatory cytokines expression. Moreover, Doxy ameliorated motor impairment and reduced striatal glial activation in A53T mice. Conclusions Our findings promote Doxy as a valuable multi-target therapeutic approach counteracting both symptoms and neuropathology in the complex scenario of α-synucleinopathies

P271 The LRRK2-R1441C mutation disrupts long-term potentiation-like plasticity in Parkinson’s disease patients

2017 ◽  
Vol 128 (9) ◽  
pp. e265
Author(s):  
Raffaele Dubbioso ◽  
Anna De Rosa ◽  
Marcello Esposito ◽  
Silvio Peluso ◽  
Rosa Iodice ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Long Term Potentiation ◽  
Term Potentiation

Synaptic dysfunction in Parkinson's disease

2010 ◽  
Vol 38 (2) ◽  
pp. 493-497 ◽  
Author(s):  
Vincenza Bagetta ◽  
Veronica Ghiglieri ◽  
Carmelo Sgobio ◽  
Paolo Calabresi ◽  
Barbara Picconi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Neurodegenerative Disorder ◽  
Long Term Potentiation ◽  
Procedural Memory ◽  
Memory Storage ◽  
Term Potentiation ◽  
Efferent Neurons

In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, but most of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia.

scholarly journals Case Studies in Neuroscience: Lack of inhibitory synaptic plasticity in the substantia nigra pars reticulata of a patient with lithium-induced tremor

2019 ◽  
Vol 122 (4) ◽  
pp. 1367-1372 ◽  
Author(s):  
Luka Milosevic ◽  
Robert F. Dallapiazza ◽  
Renato P. Munhoz ◽  
Suneil K. Kalia ◽  
Milos R. Popovic ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Affective Disorder ◽  
Brain Stimulation ◽  
Bipolar Affective Disorder ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Therapeutic Mechanism ◽  
Deep Brain

Tremor is a well-known side effect from many psychiatric medications, including lithium and dopamine antagonists. In patients whose psychiatric symptoms are stabilized and only respond to certain medications, deep brain stimulation may offer relief of the consequent motor complications. We report the case of an elderly male with disabling tremor related to lithium therapy for bipolar affective disorder, who was subsequently treated with deep brain stimulation. In this patient, we obtained recordings from the substantia nigra pars reticulata and performed a high-frequency stimulation protocol that robustly elicits long-term potentiation (LTP)-like changes in patients with Parkinson’s disease. We hypothesized that in this patient, who did not have Parkinson’s disease, the levels of inhibitory plasticity would be much greater. However, we found an unanticipated lack of plasticity in the patient with lithium-induced tremor, compared with two de novo control patients with Parkinson’s disease. This patient was successfully treated with deep brain stimulation in the vicinity of the ventral oral posterior nucleus, an area of the thalamus that receives inputs from the basal ganglia. We postulate that the lithium-induced blockade of LTP may bring about motor complications such as tremor while simultaneously contributing to the therapeutic mechanism for treating the symptoms of psychiatric disorders such as bipolar affective disorder. NEW & NOTEWORTHY Use of a dual-microelectrode technique enabled us to compare long-term potentiation (LTP)-like changes in a patient with lithium-induced tremor to that of patients with Parkinson’s disease. This study corroborated the findings in rodent brain slices that chronic lithium treatment may block LTP. Whereas a deficit in LTP may underlie the therapeutic mechanism for treating psychiatric disorders such as bipolar affective disorder, it may simultaneously contribute to consequent appearance of tremor.

scholarly journals Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

2020 ◽  
Author(s):  
Wenting Su ◽  
Jianan Yu ◽  
Min Li ◽  
Ke Wang ◽  
Chang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Synaptic Plasticity ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Motor Skills ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
6 Hydroxydopamine

Abstract Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

scholarly journals Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?

2015 ◽  
Vol 370 (1672) ◽  
pp. 20140184 ◽  
Author(s):  
Paolo Calabresi ◽  
Veronica Ghiglieri ◽  
Petra Mazzocchetti ◽  
Ilenia Corbelli ◽  
Barbara Picconi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychiatric Symptoms ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
Therapeutic Benefit ◽  
Neurodegenerative Process ◽  
Advanced Phase ◽  
The Brain

The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson's disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients.

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