Ultrastructural evidence for glutamatergic dysregulation in schizophrenia

Roberts, Rosalinda C.; McCollum, Lesley A.; Schoonover, Kirsten E.; Mabry, Samuel J; Roche, Joy K.; Lahti, Adrienne C.

doi:10.1016/j.schres.2020.01.016

Cited by 24 publications

(32 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we can assume that PV-immunopositive basket cells have the most important role in controlling the output of Betz cells. In the electron microscope, we found a small number of PV-containing terminals with asymmetric-like or intermediary (Roberts et al 2020 ) morphology, which was partially fit the classic synaptic concept of Gray’s (Klemann and Roubos 2011 ). Previous electron microscopic ultrastructural analyses did not report such phenomenon (Tigges et al 1992 ; Gatter et al 1978 ) in primate or humans.…”

Section: Discussionsupporting

confidence: 78%

“…Our question was whether these special parvalbumin-immunopositive asymmetric-like terminals—called “PSD with intermediate thickness” in the substantia nigra (Roberts et al 2020 )—co-express vGluT1 (vesicular glutamate transporter type 1, present in cortical input terminals) or vGluT2 (vesicular glutamate transporter type 2, present in subcortical input terminals). VGluT2-immunopositive terminals were visualised by DAB-Ni reaction, to observe the varicosities and examine them in the electron microscope.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Perisomatic innervation and neurochemical features of giant pyramidal neurons in both hemispheres of the human primary motor cortex

et al. 2020

View full text Add to dashboard Cite

Betz cells—the gigantopyramidal neurons found in high amount in the primary motor cortex—are among of the most characteristic neuronal cells. A part of them contains the calcium-binding protein parvalbumin (PV) in primates. However, less is known about these cells in the human motor cortex despite their important role in different neurological disorders. Therefore, the aim of our study was to investigate the neurochemical features and perisomatic input properties of Betz cells in control human samples with short post-mortem interval. We used different microscopic techniques to investigate the primary motor cortex of both hemispheres. The soma size and density, and expression of PV of the Betz cells were investigated. Furthermore, we used confocal fluorescent and electron microscopy to examine their perisomatic input. The soma size and density showed moderate variability among samples and hemispheres. Post-mortem interval and hemispherical localization did not influence these features. Around 70% of Betz cells expressed PV, but in less intensity than the cortical interneurons. Betz neurons receive dense perisomatic input, which are mostly VIAAT- (vesicular inhibitory amino acid transporter) and PV immunopositive. In the electron microscope, we found PV-immunolabelled terminals with asymmetric-like synaptic structure, too. Terminals with morphologically similar synaptic specialisation were also found among vGluT2- (vesicular glutamate transporter type 2) immunostained terminals contacting Betz cells. Our data suggest that Betz cells’ morphological properties showed less variability among subjects and hemispheres than the density of them. Their neurochemical and perisomatic input characteristics support their role in execution of fast and precise movements.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Perisomatic innervation and neurochemical features of giant pyramidal neurons in both hemispheres of the human primary motor cortex

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition to the key role in providing energy needed for the brain, mitochondria have been recognized as risk factors for mental disorders, including schizophrenia [ 74 ], bipolar disorder (BD) [ 71 ], and depression [ 75 ]. In the classical form, mitochondrial diseases are associated with the formation of complex I [ 76 ], although other mitochondrial abnormalities include oxidative damage [ 77 ], the increase in brain lactate levels as a result of abnormal glucose metabolism [ 78 ], or change in expression of mtDNA-encoded genes [ 79 , 80 ].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders

et al. 2020

View full text Add to dashboard Cite

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.

show abstract

“…The frequency of large elaborate multi-perforated synapses was equally found in axospinous synapses and synapses on dendritic shafts and was not altered in SZ [130]. These large synapses play a role in the complex interconnectivity of the nucleus accumbens, which makes it a unique feature of the human brain [130,232].…”

Section: Schizophreniamentioning

confidence: 96%

“…Several studies identified synaptic ultrastructural alterations as evidence for glutamatergic dysfunctions in SZ patients (Table 1 and Figure 1) (for a recent review, see [232]). These alterations may depend on differences in the stage of illness, medication status, and brain regions.…”

Section: Schizophreniamentioning

confidence: 99%

Glutamatergic Dysfunction and Synaptic Ultrastructural Alterations in Schizophrenia and Autism Spectrum Disorder: Evidence from Human and Rodent Studies

Eltokhi

Santuy

Merchán-Pérez

et al. 2020

IJMS

View full text Add to dashboard Cite

The correlation between dysfunction in the glutamatergic system and neuropsychiatric disorders, including schizophrenia and autism spectrum disorder, is undisputed. Both disorders are associated with molecular and ultrastructural alterations that affect synaptic plasticity and thus the molecular and physiological basis of learning and memory. Altered synaptic plasticity, accompanied by changes in protein synthesis and trafficking of postsynaptic proteins, as well as structural modifications of excitatory synapses, are critically involved in the postnatal development of the mammalian nervous system. In this review, we summarize glutamatergic alterations and ultrastructural changes in synapses in schizophrenia and autism spectrum disorder of genetic or drug-related origin, and briefly comment on the possible reversibility of these neuropsychiatric disorders in the light of findings in regular synaptic physiology.

show abstract

Ultrastructural evidence for glutamatergic dysregulation in schizophrenia

Cited by 24 publications

References 152 publications

Perisomatic innervation and neurochemical features of giant pyramidal neurons in both hemispheres of the human primary motor cortex

Perisomatic innervation and neurochemical features of giant pyramidal neurons in both hemispheres of the human primary motor cortex

The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders

Glutamatergic Dysfunction and Synaptic Ultrastructural Alterations in Schizophrenia and Autism Spectrum Disorder: Evidence from Human and Rodent Studies

Contact Info

Product

Resources

About