scholarly journals Toxoplasma induces stripping of perisomatic inhibitory synapses

2019 ◽  
Author(s):  
Gabriela L. Carrillo ◽  
Valerie A. Ballard ◽  
Taylor Glausen ◽  
Zack Boone ◽  
Joseph Teamer ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Persistent Infection ◽  
Psychiatric Illness ◽  
Parasitic Infection ◽  
Inhibitory Synapses ◽  
Current Evidence ◽  
Nerve Terminals ◽  
Phagocytic Cells ◽  
Neuronal Somata ◽  
The Brain

ABSTRACTInfection and inflammation within the brain induces changes in neuronal connectivity and function. The intracellular protozoan parasite, Toxoplasma gondii, is one pathogen that infects the brain and can cause encephalitis and seizures. Persistent infection by this parasite is also associated with behavioral alterations and an increased risk for developing psychiatric illness, including schizophrenia. Current evidence from studies in humans and mouse models suggest that both seizures and schizophrenia result from a loss or dysfunction of inhibitory synapses. In line with this, we recently reported that persistent Toxoplasma gondii infection alters the distribution of glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes GABA synthesis in inhibitory synapses. These changes could reflect a redistribution of presynaptic machinery in inhibitory neurons or a loss of inhibitory nerve terminals. To directly assess the latter possibility, we employed serial block face scanning electron microscopy (SBFSEM) and quantified inhibitory perisomatic synapses in neocortex and hippocampus following parasitic infection. Not only did persistent infection lead to a significant loss of perisomatic synapses, it induced the ensheathment of neuronal somata by phagocytic cells. Immunohistochemical, genetic, and ultrastructural analyses revealed that these phagocytic cells included reactive microglia. Finally, ultrastructural analysis identified phagocytic cells enveloping perisomatic nerve terminals, suggesting they may participate in synaptic stripping. Thus, these results suggest that microglia contribute to perisomatic inhibitory synapse loss following parasitic infection and offer a novel mechanism as to how persistent Toxoplasma gondii infection may contribute to both seizures and psychiatric illness.MAIN POINTSToxoplasma-infection leads the loss of perisomatic inhibitory synapsesPhagocytic microglia ensheath neuronal somata following Toxoplasma-infectionMicroglia contact and envelop perisomatic nerve terminals, suggesting that Toxoplasma induces synaptic stripping

scholarly journals Kejadian Depresi dan Bunuh Diri pada Penderita Toksoplasmosis

2019 ◽  
Vol 7 (3) ◽  
pp. 323
Author(s):  
Samuel Gunawan Hutajulu ◽  
Margaretha Carolina Hutajulu
Keyword(s):  
Nervous System ◽  
Toxoplasma Gondii ◽  
Parasitic Infection ◽  
Medical Personnel ◽  
Pharmacological Therapy ◽  
The Impact ◽  
The Relationship ◽  
The Brain ◽  
Keywords Suicide ◽  
Psychiatric Problems

Infeksi parasit Toxoplasma gondii telah menjangkiti hampir seluruh penduduk di dunia. Gejala toksoplasmosis yang muncul pada individu beresiko seperti bayi, ibu hamil dan penderita imunokompromais ternyata dapat muncul juga pada individu imunokompeten. Ookista yang menimbulkan toksoplasmosis kronis di otak, mampu memengaruhi sistem saraf dan kejiwaan penderitanya. Banyak bukti yang menunjukkan hubungan antara munculnya afek depresi pada individu dengan peningkatan serum anti toksoplasma. Depresi yang berkepanjangan tanpa intervensi tenaga medis, baik terapi farmakologi maupun terapi non-farmakologi memunculkan pikiran bunuh diri pada penderita. Tujuan penelitian ini untuk menguraikan dampak dari penyakit toksoplasmosis yang tidak ditangani sehingga memunculkan berbagai macam gangguan psikiatri khususnya depresi dan bunuh diri. Penelitian ini merupakan hasil dari penelaahan pustaka dengan metode pencarian literatur yang dilakukan di internet dan buku teks berdasarkan pertanyaan mengenai patofisiologi penyakit toksoplasmosis yang terjadi dalam struktur anatomi sistem saraf pusat-perifer dan jalur neurotransmitter sehingga berakibat pada depresi dan ingin bunuh diri. Sumber pustaka terbaru dalam jangka waktu 15 tahun terakhir berjumlah 27 buah. Sebagai kesimpulan didapatkan gangguan keseimbangan neurotransmitter dopamin, serotonin dan glutamat serta perubahan pada kerusakan sel glial, amigdala dan korteks prefrontal yang menyebabkan perubahan suasana hati depresif pada penderita toksoplasmosis kronis. Kata kunci : bunuh diri, depresi, inflamasi, neurotransmiter, toksoplasmosis EVENT OF DEPRESSION AND SUICIDE IN PEOPLE WITH TOXOPLASMOSIS ABSTRACTThe parasitic infection of Toxoplasma gondii has infected almost population in the world. The fact that toxoplasmosis arises in at-risk persons such as infants, pregnant women and immunocompromised patients can also appear in immunocompetent individuals. Oocysts causes’ chronic toxoplasmosis in the brain, can affect the patient’s nervous system and psychiatric. There is a lot of evidence shows the relationship between emergence of depression’s affect in person with an increase of serum anti-toxoplasma. Prolonged depression without intervention from medical personnel, both pharmacological therapy and non-pharmacological therapy, raises thoughts of suicide in the patients. The purpose of this study is to describe the impact of toxoplasmosis which is not handled up so as bring up variety of psychiatric problems specifically depression and suicide. This paper is the result of a literature review using a literature search method on the internet and textbook conduction by questions about the pathophysiology of the disease that occurs in the anatomy of the central-peripheral nervous system and neurotransmitters that cause depression and commit to suicide. The latest sources of literature in the last 15 years replacement of 27 sources. In conclusion, disorders of the neurotransmitter dopamine, serotonin and glutamate balance and changes in glial cell, amygdala and prefrontal cortex may cause changes in patients mood with chronic toxoplasmosis. Keywords : suicide, depression, inflammation, neurotransmitter, toxoplasmosis

scholarly journals The Excitatory/Inhibitory Balance of Synaptic Transmission Is Impaired at Higher Extracellular Ca2+ Concentrations in Scn1a+/− Mouse Model of Dravet Syndrome

2021 ◽  
Author(s):  
Kouya Uchino ◽  
Hiroyuki Kawano ◽  
Yasuyoshi Tanaka ◽  
Yuna Adaniya ◽  
Ai Asahara ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dravet Syndrome ◽  
Inhibitory Synapses ◽  
Nerve Terminals ◽  
Wild Type ◽  
Postsynaptic Currents ◽  
Vesicular Release ◽  
A Subunit ◽  
Proportional Increase ◽  
The Brain

Abstract Dravet syndrome (DS) is an intractable form of childhood epilepsy that occurs in infancy. More than 80% of all patients have a heterozygous abnormality in the SCN1A gene, which encodes a subunit of Na+ channels in the brain. However, the detailed pathogenesis of DS remains unclear. This study investigated the synaptic pathogenesis of this disease in terms of excitatory/inhibitory balance using a mouse model of DS. We show that excitatory postsynaptic currents were similar between Scn1a knock-in neurons (Scn1a+/− neurons) and wild-type neurons, but inhibitory postsynaptic currents were significantly lower in Scn1a+/− neurons. Moreover, both the vesicular release probability and the number of inhibitory synapses were significantly lower in Scn1a+/− neurons compared with wild-type neurons. There was no proportional increase in inhibitory postsynaptic current amplitude in response to increased extracellular Ca2+ concentrations. Our study revealed that the number of inhibitory synapses is significantly reduced in Scn1a+/− neurons, while the sensitivity of inhibitory synapses to extracellular Ca2+ concentrations is markedly increased. These data suggest that Ca2+ tethering in inhibitory nerve terminals may be disturbed following the synaptic burst, likely leading to epileptic symptoms.

scholarly journals The excitatory/inhibitory balance of synaptic transmission is impaired at higher extracellular Ca2+ concentrations in Scn1a+/− mouse model of Dravet syndrome

2021 ◽  
Author(s):  
Kouya Uchino ◽  
Hiroyuki Kawano ◽  
Yasuyoshi Tanaka ◽  
Yuna Adaniya ◽  
Ai Asahara ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dravet Syndrome ◽  
Inhibitory Synapses ◽  
Nerve Terminals ◽  
Wild Type ◽  
Postsynaptic Currents ◽  
Vesicular Release ◽  
A Subunit ◽  
Proportional Increase ◽  
The Brain

AbstractDravet syndrome (DS) is an intractable form of childhood epilepsy that occurs in infancy. More than 80% of all patients have a heterozygous abnormality in the SCN1A gene, which encodes a subunit of Na+ channels in the brain. However, the detailed pathogenesis of DS remains unclear. This study investigated the synaptic pathogenesis of this disease in terms of excitatory/inhibitory balance using a mouse model of DS. We show that excitatory postsynaptic currents were similar between Scn1a knock-in neurons (Scn1a+/− neurons) and wild-type neurons, but inhibitory postsynaptic currents were significantly lower in Scn1a+/− neurons. Moreover, both the vesicular release probability and the number of inhibitory synapses were significantly lower in Scn1a+/− neurons compared with wild-type neurons. There was no proportional increase in inhibitory postsynaptic current amplitude in response to increased extracellular Ca2+ concentrations. Our study revealed that the number of inhibitory synapses is significantly reduced in Scn1a+/− neurons, while the sensitivity of inhibitory synapses to extracellular Ca2+ concentrations is markedly increased. These data suggest that Ca2+ tethering in inhibitory nerve terminals may be disturbed following the synaptic burst, likely leading to epileptic symptoms.

Computer-Assisted Analysis of Multi-Color Confocal Microscopic Datasets: Automated Light Microscopic Discrimination of Synaptic Relationships

1996 ◽  
Vol 54 ◽  
pp. 284-285
Author(s):  
M Wessendorf ◽  
A Beuning ◽  
D Cameron ◽  
J Williams ◽  
C Knox
Keyword(s):  
Nerve Fibers ◽  
Confocal Scanning Laser Microscopy ◽  
Computer Assisted ◽  
Nerve Terminals ◽  
Neuronal Somata ◽  
Scanning Laser Microscopy ◽  
Confocal Scanning ◽  
Entire Cell ◽  
Confocal Scanning Laser ◽  
Assisted Analysis

Multi-color confocal scanning-laser microscopy (CSLM) allows examination of the relationships between neuronal somata and the nerve fibers surrounding them at sub-micron resolution in x,y, and z. Given these properties, it should be possible to use multi-color CSLM to identify relationships that might be synapses and eliminate those that are clearly too distant to be synapses. In previous studies of this type, pairs of images (e.g., red and green images for tissue stained with rhodamine and fluorescein) have been merged and examined for nerve terminals that appose a stained cell (see, for instance, Mason et al.). The above method suffers from two disadvantages, though. First, although it is possible to recognize appositions in which the varicosity abuts the cell in the x or y axes, it is more difficult to recognize them if the apposition is oriented at all in the z-axis—e.g., if the varicosity lies above or below the neuron rather than next to it. Second, using this method to identify potential appositions over an entire cell is time-consuming and tedious.

Dementia, Cognitive Deficit, Headache? Think Parasitic Infection of the Brain

2008 ◽  
Vol 38 (11) ◽  
pp. 36
Author(s):  
AMY ROTHMAN SCHONFELD
Keyword(s):  
Cognitive Deficit ◽  
Parasitic Infection ◽  
The Brain

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

Brain Parasites and Suicide

2010 ◽  
Vol 107 (2) ◽  
pp. 424-424 ◽  
Author(s):  
David Lester
Keyword(s):  
Toxoplasma Gondii ◽  
Men And Women ◽  
Suicide Rates ◽  
The Brain

In a sample of 20 European nations, the prevalence of the brain parasite Toxoplasma gondii was positively associated with national suicide rates for men and women.

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