Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss

Talantova, Maria; Sanz-Blasco, Sara; Zhang, Xiaofei; Xia, Peng; Akhtar, Mohd Waseem; Okamoto, Shu-ichi; Dziewczapolski, Gustavo; Nakamura, Tomohiro; Cao, Gang; Pratt, Alexander E.; Kang, Yeon-Joo; Tu, Shichun; Molokanova, Elena; McKercher, Scott R.; Hires, Samuel Andrew; Sason, Hagit; Stouffer, David G.; Buczynski, Matthew W.; Solomon, James P.; Michael, Sarah; Powers, Evan T.; Kelly, Jeffery W.; Roberts, Amanda J.; Tong, Gary; Fang-Newmeyer, Traci; Parker, James D. A.; Holland, Emily A.; Zhang, Dongxian; Nakanishi, Norihiko; Chen, H.-S. Vincent; Wolosker, Herman; Wang, Yuqiang; Parsons, Loren H.; Ambasudhan, Rajesh; Masliah, Eliezer; Heinemann, Stephen F.; Piña‐Crespo, Juan C.; Lipton, Stuart A.

doi:10.1073/pnas.1306832110

Cited by 514 publications

(570 citation statements)

References 69 publications

(154 reference statements)

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“…Along with this, increasing evidence shows the active involvement of astrocytes in synapse formation, function, and elimination (Clarke and Barres, 2013). Talantova et al in particular showed the involvement of astrocytes in glutamate-induced synaptic damage via a-7 nicotinic receptors stimulation and extrasynaptic N-methyl-d-aspartateetype glutamate receptors (Talantova et al, 2013). In comparison, our study focuses on glutamate regulation via GLT-1 expression.…”

Section: Discussionmentioning

confidence: 75%

Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease

Zumkehr

Rodriguez‐Ortiz

Cheng

et al. 2015

Neurobiology of Aging

134

106

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TauAmyloid b a b s t r a c t Glial glutamate transporter, GLT-1, is the major Na þ -driven glutamate transporter to control glutamate levels in synapses and prevent glutamate-induced excitotoxicity implicated in neurodegenerative disorders including Alzheimer's disease (AD). Significant functional loss of GLT-1 has been reported to correlate well with synaptic degeneration and severity of cognitive impairment among AD patients, yet the underlying molecular mechanism and its pathological consequence in AD are not well understood.Here, we find the temporal decrease in GLT-1 levels in the hippocampus of the 3xTg-AD mouse model and that the pharmacological upregulation of GLT-1 significantly ameliorates the age-dependent pathological tau accumulation, restores synaptic proteins, and rescues cognitive decline with minimal effects on Ab pathology. In primary neuron and astrocyte coculture, naturally secreted Ab species significantly downregulate GLT-1 steady-state and expression levels. Taken together, our data strongly suggest that GLT-1 restoration is neuroprotective and Ab-induced astrocyte dysfunction represented by a functional loss of GLT-1 may serve as one of the major pathological links between Ab and tau pathology.

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Section: Discussionmentioning

confidence: 75%

Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease

Zumkehr

Rodriguez‐Ortiz

Cheng

et al. 2015

Neurobiology of Aging

134

106

View full text Add to dashboard Cite

show abstract

“…Therefore, mEPSCs may have a critical role in the functional and structural aspects of the synapses of PNs (32). Talantova et al (33) previously demonstrated that a decreased frequency of mEPSCs may cause early synaptic injury, due to concurrent extrasynaptic N-methyl-D-aspartare receptor-mediated nitric oxide production, tau phosphorylation, and caspase-3 activation.…”

Section: Discussionmentioning

confidence: 99%

Effects of sevoflurane on leucine-rich repeat kinaseï¿½2-associated Drosophila model of Parkinson's disease

et al. 2014

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Abstract.Patients with Parkinson's disease (PD) often require surgery, and therefore may receive inhalation anesthesia. However, it is currently unknown whether inhalation anesthetics affect the prognosis of the disease. Leucine-rich repeat kinase 2 (LRRK2) genetic mutations are the most common cause of familial PD, contributing to ~39% of all cases in certain populations. The aim of the present study was to determine the effects of inhaled anesthetics on PD, by observing the influence of sevoflurane on a LRRK2-associated Drosophila model of PD. PD transgenic Drosophila overexpressing LRRK2 were generated by crossing flies expressing an LRRK2 upstream activation sequence, with tyrosine hydroxylase (TH)-Gal4 flies. Western blot analysis successfully verified that the transgenic Drosophila overexpressed LRRK2. Three days prior to eclosion, three genotypes of Drosophila were divided into four groups, and were exposed to air, 1, 2, or 3% sevoflurane, for 5 hours. Twenty-four hours after the exposure, the electrophysiological activities of the projection neurons (PN) in the brains of the Drosophila were recorded using a patch clamp. The locomotor activities were tested on days 5,10,15,20, 25,30,35 and 40 following eclosion. The frequency of miniature excitatory synaptic currents (mEPSCs) obtained from the PNs of the TH-wild type LRRK2 (TH-WT) Drosophila brain, following exposure to air (1.60±0.05 Hz), was lower as compared with the wild type LRRK2 (WT) (2.51±0.07 Hz) and W1118 (2.41±0.10 Hz) Drosophila. After exposure to 1, 2 and 3% sevoflurane, the frequency of mEPSCs in the brains of the TH-WT group decreased to 0.82±0.04 Hz, 0.63±0.16 Hz and 0.55±0.04 Hz, respectively. The percentage decrease of the frequency of mEPSCs, from exposure to air to 1% sevoflurane, of the TH-WT group (48.32%±3.08%) was significantly higher, as compared with the WT (39.17%±1.42%) and W1118 (35.10%±2.66%) groups, and there was no statistical difference between the WT and W1118 groups. The transgenic TH-WT Drosophila presented an early decrease in locomotor ability, as compared with the WT and W1118 groups. Following a 5 hour exposure to sevoflurane, the percentage decrease of the climbing abilities of the TH-WT group, from exposure to air to 1% sevoflurane, were significantly lower, as compared with the WT and W1118 groups. In conclusion, sevoflurane had negative effects on the control W1118 flies, and also severely aggravated the prognosis of PD in the LRRK2-associated Drosophila model, through synaptic cholinergic deficits and impairment on locomotor abilities.

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“…The degeneration of cholinergic neurons across the basal forebrain, especially in the nucleus basalis of Meynert (NBM), is responsible for the cholinergic deficiency observed in the brains of AD patients [18]. The early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs), characterized by decreased production of acetylcholine (ACh) substantially contributes to the gradual cognitive decline in AD [157].…”

Section: Psycho-behavioural Anomalies As Diagnostic Marker For Neurolmentioning

confidence: 99%

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

Choudhury¹,

Sahu²,

Ramanujam³

et al. 2018

Neuropsychiatry

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Structural changes in different regions of the brain have become clinically relevant and regarded as the signature phenomenon for neurological diseases. Morphological changes in brain are also associated with neuronal and neurochemical alterations. Studies have showed that minute changes in neurochemical levels may have marked impact on the psychobehaviour of the subject. Several neurological disease profiles have been reported with such specific psychobehavioural expression. However, application of behavioural abnormalities as possible disease progress markers has not been considered and emphasised much. Reports suggested that-the subjects, who have already entered into the terminal stage of the disease, used to show cardinal behavioural signs for a specific disease profile. However, psychological expressions are comparatively early expressive. As most of the neurodegenerative disorders are unidirectional and progressive by nature, therapeutic intervention at the right time is essential for attaining the desired outcome. Moreover, early diagnosis can aid in managing the disease progression also. Psychobehavioural analysis could meet the expected outcome of disease diagnosis if implemented properly and timely. In the present review, we have amalgamated the reported behavioural anomalies with the supportive background from neurochemical basis. Further, we have concluded that behaviour centric studies could be a potential diagnostic tool for the early diagnosis of major neurological diseases such as Alzheimer disease, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), Bipolar disorder, Schizophrenia, Impulse control disorder (ICD) and Obsessive-compulsive disorder (OCD).

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Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss

Cited by 514 publications

References 69 publications

Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease

Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease

Effects of sevoflurane on leucine-rich repeat kinaseï¿½2-associated Drosophila model of Parkinson's disease

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

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