Is a herpes viral protein responsible for foci of alarming presence of T cells in the brain of schizophrenia patients?

Schizophrenia (SZ) is a devastating disease with a life time incidence of 1%. The distinguishing symptoms for diagnosis of the disorder are thought disorders like formal incoherence of thoughts, but also bizarre contents of thoughts, like thoughts been taken over by foreign powers and among the symp...
Ausführliche Beschreibung

Schizophrenia (SZ) is a devastating disease with a life time incidence of 1%. The distinguishing symptoms for diagnosis of the disorder are thought disorders like formal incoherence of thoughts, but also bizarre contents of thoughts, like thoughts been taken over by foreign powers and among the symptoms are also hallucinations. Treatment with antipsychotics suppresses these psychotic symptoms (called positive, because normally not present in health persons), but patients remain handicapped in cognition, initiative and executive functions (called negative symptoms, because normally present in healthy individuals). The cause of psychosis and diagnostically “ensuing” SZ is an enigma, albeit genetic, imaging and post-mortem research indicate an inflammatory origin of the disease. In a recent opinion paper on the inflammatory origins of SZ, Corsi Zuelli, elegantly summarized the literature regarding the inflammation hypothesis, showing that presence of activated immune cells in the brain (microglia) might actually be immune repressive, and TGF-beta might be the major inhibitory immune factor explaining disturbances in the development of connections in the maturing human brain in adult life as observed in SZ. The brain is an immune privileged site, potent pro-inflammatory proteins like LPS (lipopolysaccharides) that result in oedema, microvascular proliferation and influx of macrophages shedding toxic cytokines in the periphery, do not mount a particularly strong response in the brain, preventing oedema, intracranial hypertension and death (when intracranial pressure exceeds the systolic blood pressure blood supply halts). Very potent anti-inflammatory mechanisms are in place. Therefore, a notable increase of the anti-inflammatory protein TGF-beta in the SZ brain, might indicate a strong trigger for inflammation, which needs to be suppressed and inflict exhaustion to prevent a too forceful pro-inflammatory response to prevent brain damage. No inflammatory damage has been found in SZ brain, like in bacterial or viral encephalitis, where glial scarring is a late sign of inflammatory damage. However, latent infections with known viruses, are present in the brain in many healthy individuals and as a rule do not cause full-blown encephalitis but still need a chronic inflammatory response to be kept latent. Of particular interest in this respect is HSV-1, which colonizes limbic regions of the brain, a region intrinsically associated with SZ (and psychotic mood disorders). Inflammatory changes in the hippocampal region occur both in herpes infections and psychotic disorders. In clinical herpes infections of the brain (severe encephalitis) major hippocampal volume reduction ensues after protracted inflammation (as imaged with PET). In SZ, hippocampal volume already becomes reduced, before the first psychosis sets in. Alzheimers’ disease (AD) is characterized by psychosis but cognitive decline (“negative symptoms”) predominate. Defining MRI feature of AD is a major reduction in hippocampal volume in addition to the cognitive, executive, and emotional changes of far more severity as in SZ. However, also in AD HSV-1 might be involved in the AD typical accumulation of toxic proteins like Abeta, with ensuing inflammation. Post mortem research in SZ shows that an inflammatory response is taking place, with HLA-DR presenting cells accumulating in various brain regions. Also T-cell infiltrates are present, which might indicate the encounter with (viral) proteins or DNA. It still remains unknown, whether the phenotype of these antigen presenting HLA-DR+ cells and T-cells are pro-inflammatory or are in contrast anti-inflammatory/exhausted. This presentation will address the proteins of the replication machinery that have a direct role in the inflammatory response early (in the first infection/psychotic episode) and might be found as tracers of the first encounter of the virus in post-mortem brains of SZ and AD patients alike. Ausführliche Beschreibung

Autor*in:	Hans C. Klein [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: Journal of Affective Disorders Reports - Elsevier, 2021, 12(2023), Seite 100550-
Übergeordnetes Werk:	volume:12 ; year:2023 ; pages:100550-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.jadr.2023.100550

Katalog-ID:	DOAJ088823229