The Selective Regional Vulnerability of the Brain and its Relation to Psychiatric Problems

Epilepsy which is also called seizures disorder is an uncontrolled action of the central nervous system. Itis not a single disease but a set of neurological disorders. Actually in this situation, the brain does notreceive a precise signal and as a result an abnormal condition is produced that is usually involuntary inaction. In this review, we aimed to focus on the relationship of anti-epileptic drugs with sexual dysfunctionand adaptation of better remedies that improve a patient’s family life. Sexual dysfunction is a commoncomorbidity in people with epilepsy which badly affects their quality of life. Sexual dysfunction is causedby different factors like psychiatric problems, anti-epileptic drugs (AEDs) and social factors etc. Sexualdysfunctions include ejaculatory failure, lessen libido, penile erection in men and irregular menstrual cyclein women. Common drugs such as Topiramate, Gabapentin (GBP), Valproate (VA), Carbamazepine (CBZ),Olanzapine (OL) and Risperidone (RTG) that are in practice to treat epilepsy usually produced adverseeffect on sexual dysfunction. Even though a lot of studies have been carried out to control sexualdysfunction in epilepsy’s patient, but still research is going on. Medicine such as Cyproheptadine,Mianserin, Buspirone, Yohimbine were found better to treat epilepsy with minimum side effects of sexualdysfunction. Moreover, it is also seen that certain vasodilators, folate , and vitamin supplements areeffective in improving the quality of life.

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Reduction of cortical parvalbumin expressing GABAergic interneurons in a rodent hyperoxia model of preterm birth brain injury with deficits in social behavior and cognition

Development ◽

10.1242/dev.198390 ◽

2021 ◽

Author(s):

Till Scheuer ◽

Elena auf dem Brinke ◽

Sabine Grosser ◽

Susanne A. Wolf ◽

Daniele Mattei ◽

...

Keyword(s):

Preterm Birth ◽

Psychiatric Symptoms ◽

Autism Spectrum ◽

Morphological Properties ◽

Behavioral Deficits ◽

Hyperactivity Disorder ◽

Spectrum Disorders ◽

The Brain ◽

Psychiatric Problems ◽

Behavior And Cognition

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the mechanisms underlying are not known. In a translational hyperoxia model, exposing mice pups at age P5 to 80% oxygen for 48 hours to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin expressing interneurons until adulthood. Developmental delay of cortical myelin was observed together with decreased expression of oligodendroglial glial cell-derived neurotrophic factor (GDNF), a factor being involved in interneuronal development. Electrophysiological and morphological properties of remaining interneurons were unaffected. Behavioral deficits were observed for social interaction, learning, and attention. These results elucidate that neonatal oxidative stress can lead to decreased interneuron density and to psychiatric symptoms. The obtained cortical myelin deficit and decreased oligodendroglial GDNF expression indicate an impaired oligodendroglial-interneuronal interplay contributes to interneuronal damage.

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Experimental evidence for the age dependence of tau protein spread in the brain

Science Advances ◽

10.1126/sciadv.aaw6404 ◽

2019 ◽

Vol 5 (6) ◽

pp. eaaw6404 ◽

Cited By ~ 22

Author(s):

Susanne Wegmann ◽

Rachel E. Bennett ◽

Louis Delorme ◽

Ashley B. Robbins ◽

Miwei Hu ◽

...

Keyword(s):

Tau Protein ◽

Brain Region ◽

Age Dependence ◽

Tau Pathology ◽

Related Factors ◽

Age Related ◽

Regional Vulnerability ◽

Related Risk ◽

Old Mice ◽

The Brain

The incidence of Alzheimer’s disease (AD), which is characterized by progressive cognitive decline that correlates with the spread of tau protein aggregation in the cortical mantle, is strongly age-related. It could be that age predisposes the brain for tau misfolding and supports the propagation of tau pathology. We tested this hypothesis using an experimental setup that allowed for exploration of age-related factors of tau spread and regional vulnerability. We virally expressed human tau locally in entorhinal cortex (EC) neurons of young or old mice and monitored the cell-to-cell tau protein spread by immunolabeling. Old animals showed more tau spreading in the hippocampus and adjacent cortical areas and accumulated more misfolded tau in EC neurons. No misfolding, at any age, was observed in the striatum, a brain region mostly unaffected by tangles. Age and brain region dependent tau spreading and misfolding likely contribute to the profound age-related risk for sporadic AD.

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246 Bilirubin in the Brain: Neurotoxic Effects, Therapeutic Promises and Regional Vulnerability

Pediatric Research ◽

10.1203/00006450-201011001-00246 ◽

2010 ◽

Vol 68 ◽

pp. 128-128

Author(s):

A R Vaz ◽

S L Silva ◽

A S Falcão ◽

A Barateiro ◽

A Fernandes ◽

...

Keyword(s):

Regional Vulnerability ◽

Neurotoxic Effects ◽

The Brain

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Computational modeling of tau pathology spread reveals patterns of regional vulnerability and the impact of a genetic risk factor

Science Advances ◽

10.1126/sciadv.abg6677 ◽

2021 ◽

Vol 7 (24) ◽

pp. eabg6677

Author(s):

Eli J. Cornblath ◽

Howard L. Li ◽

Lakshmi Changolkar ◽

Bin Zhang ◽

Hannah J. Brown ◽

...

Keyword(s):

Expression Patterns ◽

Brain Regions ◽

Spatial Proximity ◽

Leucine Rich Repeat ◽

Related Gene ◽

Tau Pathology ◽

Anatomical Connectivity ◽

Regional Vulnerability ◽

The Impact ◽

The Brain

Neuropathological staging studies have suggested that tau pathology spreads through the brain in Alzheimer’s disease (AD) and other tauopathies, but it is unclear how neuroanatomical connections, spatial proximity, and regional vulnerability contribute. In this study, we seed tau pathology in the brains of nontransgenic mice with AD tau and quantify pathology development over 9 months in 134 brain regions. Network modeling of pathology progression shows that diffusion through the connectome is the best predictor of tau pathology patterns. Further, deviations from pure neuroanatomical spread are used to estimate regional vulnerability to tau pathology and identify related gene expression patterns. Last, we show that pathology spread is altered in mice harboring a mutation in leucine-rich repeat kinase 2. While tau pathology spread is still constrained by anatomical connectivity in these mice, it spreads preferentially in a retrograde direction. This study provides a framework for understanding neuropathological progression in tauopathies.

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A hypothesis: King Henry VIII’s (1491–1547) personality change: A case of lead poisoning?

Journal of Medical Biography ◽

10.1177/0967772017694571 ◽

2017 ◽

Vol 25 (2) ◽

pp. 72-80 ◽

Cited By ~ 1

Author(s):

Anne Charlton

Keyword(s):

Lead Poisoning ◽

Personality Change ◽

British Library ◽

Henry Viii ◽

Leg Ulcers ◽

Before And After ◽

The Brain ◽

Psychiatric Problems

Henry VIII (1491–1547) became King of England in 1509. He started out as a good monarch, sensible, reasonable and pleasant, but later his behaviour changed drastically. He became irascible, intolerant, violent and tyrannical. In January 1536, Henry had a serious jousting accident and was unconscious for 2 h. It is generally believed that this accident played a major role in his personality change. Letters of that time, however, indicate that the change began insidiously in 1534 and became most drastic in 1535, a year before the accident. Henry had suffered from leg ulcers before and after the accident and had been constantly treated for them for many years. Sloane MS1047, now in the British Library in London, contains the prescriptions for the medications used to treat these ulcers. Many of the medications contain a high proportion of lead in various forms. Lead can be absorbed through skin, especially damaged skin. Absorbed lead can affect the brain, causing psychiatric problems, especially those associated with violence. The author presents a hypothesis that absorbed lead from his medications might have been a major factor in King Henry’s personality change.

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The basis of clinicopathological heterogeneity in TDP-43 proteinopathy

Acta Neuropathologica ◽

10.1007/s00401-019-02077-x ◽

2019 ◽

Vol 138 (5) ◽

pp. 751-770 ◽

Cited By ~ 13

Author(s):

Ito Kawakami ◽

Tetsuaki Arai ◽

Masato Hasegawa

Keyword(s):

Distribution Patterns ◽

Cell Types ◽

Brain Regions ◽

Cytoplasmic Inclusions ◽

Clinical Phenotypes ◽

Regional Vulnerability ◽

Key Issues ◽

Future Therapy ◽

The Brain ◽

Lateral Sclerosis

Abstract Transactive response DNA-binding protein 43 kDa (TDP-43) was identified as a major disease-associated component in the brain of patients with amyotrophic lateral sclerosis (ALS), as well as the largest subset of patients with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), which characteristically exhibits cytoplasmic inclusions that are positive for ubiquitin but negative for tau and α-synuclein. TDP-43 pathology occurs in distinct brain regions, involves disparate brain networks, and features accumulation of misfolded proteins in various cell types and in different neuroanatomical regions. The clinical phenotypes of ALS and FTLD-TDP (FTLD with abnormal intracellular accumulations of TDP-43) correlate with characteristic distribution patterns of the underlying pathology across specific brain regions with disease progression. Recent studies support the idea that pathological protein spreads from neuron to neuron via axonal transport in a hierarchical manner. However, little is known to date about the basis of the selective cellular and regional vulnerability, although the information would have important implications for the development of targeted and personalized therapies. Here, we aim to summarize recent advances in the neuropathology, genetics and animal models of TDP-43 proteinopathy, and their relationship to clinical phenotypes for the underlying selective neuronal and regional susceptibilities. Finally, we attempt to integrate these findings into the emerging picture of TDP-43 proteinopathy, and to highlight key issues for future therapy and research.

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Tau pathology spreads between anatomically-connected regions of the brain and is modulated by a LRRK2 mutation

10.1101/2020.10.13.337857 ◽

2020 ◽

Author(s):

Michael X. Henderson ◽

Eli J. Cornblath ◽

Howard L. Li ◽

Lakshmi Changolkar ◽

Bin Zhang ◽

...

Keyword(s):

Expression Patterns ◽

Network Models ◽

Spatial Proximity ◽

Spatiotemporal Pattern ◽

Diagnostic Feature ◽

Tau Pathology ◽

Anatomical Connectivity ◽

Regional Vulnerability ◽

Kinetics Of ◽

The Brain

ABSTRACTTau pathology is a diagnostic feature of Alzheimer’s disease (AD) but is also a prominent feature of Parkinson’s disease (PD), including genetic forms of PD with mutations in leucine-rich repeat kinase 2 (LRRK2). In both diseases, tau pathology is progressive and correlates with cognitive decline. Neuropathological staging studies in humans and mouse models have suggested that tau spreads through the brain, but it is unclear how neuroanatomical connections, spatial proximity, and regional vulnerability contribute to pathology spread. Further, it is unknown how mutations in the LRRK2 gene may modulate susceptibility to tau pathology’s initiation or spread. In this study, we used seed-based models of tauopathy to capture spatiotemporal patterns of pathology in mice. Following the injection of AD brain-derived tau into the brains of non-transgenic mice, tau pathology spreads progressively through the brain in a spatiotemporal pattern that is well-explained by anatomical connectivity. We validated and compared network models based on diffusion along anatomical connections to predict tau spread, estimate regional vulnerability to tau pathology, and investigate gene expression patterns related to regional vulnerability. We further investigated tau pathology spread in mice harboring a mutation in LRRK2 and found that while tau pathology spread is still constrained by anatomical connectivity, it spreads preferentially in a retrograde direction to regions that are otherwise resilient in wildtype mice. This study provides a quantitative demonstration that tau pathology spreads along anatomical connections, explores the kinetics of this spread, and provides a platform for investigating the effect of genetic risk factors and treatments on the progression of tauopathies.

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Kejadian Depresi dan Bunuh Diri pada Penderita Toksoplasmosis

Jurnal Keperawatan Jiwa ◽

10.26714/jkj.7.3.2019.323-332 ◽

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

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