Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates

Gosztonyi, Georg; Ludwig, Hanns; Bode, Liv; Kao, Moujahed; Sell, Manfred; Petrusz, Peter; Halász, Béla

doi:10.1007/s00429-020-02063-0

Cited by 6 publications

(6 citation statements)

References 162 publications

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“…Given that the early reservoir treated animals never developed clinical signs of signi cant ICP elevation but did have demonstrable ventricular enlargement on MRI, physical stress in the form of stretch injury to the ependymal lining and compressive injury to the immediate PV brain may have initiated an injury cascade permitting prolonged changes in glymphatic proteins at sacri ce. Our group and others have demonstrated that even short periods of time under pathological pressure can be detrimental to not only ependymal cilia, but also damage developing brain cells (12,21,(30)(31)(32)(33)(34)(35)(36)(37)(38). When comparing the two treatment groups, late-treated animals demonstrated even more substantial decrease in AQP4 within the PV region, as well as signi cantly diminished GFAP signal in the same region, compared with early and control groups.…”

Section: Periventricular Regionmentioning

confidence: 74%

Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus

Vasas¹,

McAllister²,

Eskandari³

2021

Preprint

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Background Changes in aquaporin-4 (AQP4) and glial fibrillary acid protein (GFAP) expression by astrocytes have been observed in several pathologies. It is hypothesized that prolonged exposure to pathologically elevated intracranial pressure (ICP) may be linked to impaired glymphatic pathways. In this study we explore histological consequences of prolonged pressure-induced injury in a feline model of neonatal hydrocephalus through changes in AQP4 and GFAP expression. We discuss the implications this may have in gaining a better understanding of the underlying mechanisms of hydrocephalus (HCP). Methods Using a neonatal feline model, obstructive HCP was induced through kaolin injection into the cisterna magna. Time between injection and intervention via ventricular reservoir placement was used to divide groups into early and late treatment groups. Early and late animals received reservoirs at 1- and 2-weeks post kaolin injection, respectively. Controls underwent sham operations (saline injection instead of kaolin). Animals were sacrificed at 4 months allowing for a chronic treated hydrocephalic model at time of brain harvest. Immunofluorescent staining for GFAP, AQP4 and DAPI was performed on histological brain sections from each group, and densitometry was used to quantify the relative signal of protein expression. Results Hydrocephalus was seen in all animals receiving kaolin injection as demonstrated by magnetic resonance imaging, clinical examination and neurological sequelae. Hydrocephalic animals demonstrated lower levels of perivascular AQP4 expression, increased diffuse AQP4 expression and increased glial scarring of perivascular, ependymal and subependymal spaces. Cerebral microvasculature of early treatment groups demonstrated increased astrocytic processes in the perivascular spaces, while late treatment groups demonstrated increased glial scar formation. Overall, the glymphatic system was severely disrupted in chronic treated hydrocephalus compared to controls. Conclusions Reactive astrogliosis and AQP4 mislocation are evident in early and late reservoir-treated HCP. Glial scarring in the perivascular, ependymal and subependymal spaces concurrent with AQP4 internalization from the perivascular region are prominent in HCP conditions present within the neonatal period. Delay in treatment by 1 week demonstrates quantifiable increases in perivascular and ependymal glial scarring at 4 months of age. Further investigation is needed to correlate glymphatic disruption with impaired CSF absorption and its role in promoting progressive hydrocephalus.

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Section: Periventricular Regionmentioning

confidence: 74%

Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus

Vasas¹,

McAllister²,

Eskandari³

2021

Preprint

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“…Among other changes, they observed an increase in NPY mRNA levels in the cerebral cortex hippocampus and hypothalamus at 28 days post-infection. Bornaviruses are among those viruses that can induce behavioral changes resulting in obesity [21].…”

Section: Discussionmentioning

confidence: 99%

The Pathogenesis of Proventricular Dilatation Disease Caused by Parrot Bornaviruses: A Possible Role For Neuropeptide Y (Npy)

Chen

Guo

Yan

et al. 2020

Preprint

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Background Psittacine Bornaviruses cause a unique disease syndrome in parrots and related birds. Known as proventricular dilatation disease (PDD), it is characterized by massive dilatation of their proventriculus as a result of excessive food accumulation within that organ. This leads to gastric obstruction and eventually, to death by starvation. Results In a preliminary study on the transcriptome of psittacine bornavirus-infected human astroglia it was noted that the gene encoding neuropeptide Y was significantly upregulated. In a subsequent study of cockatiels experimentally infected with the same strain of psittacine bornavirus, their brains were examined by RNA-seq to determine which genes were being actively transcribed. It was confirmed that among the genes whose expression was significantly increased relative to control, uninfected birds was that for neuropeptide Y. Conclusions Neuropeptide Y is known to cause overeating in birds. We hypothesize therefore that the clinical manifestations of proventricular dilatation disease are a result of the excessive production of neuropeptide Y by bornavirus-infected brain cells acting in association with damage to the neurons of the proventricular myenteric plexus.

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“…Intracerebral infection of rats with a BDV variant induced obesity without neurological signs, which is correlated with severe mononuclear cell infiltration into the hypothalamus, suggesting that infection-induced neuroendocrine dysregulations caused the development of obesity (Herden et al, 2000). It was also suggested that BDV infection-induced neuroinflammation and neurotransmitter imbalance underlie the dysfunction of hypothalamus and leptin resistance, leading to obesity (Gosztonyi et al, 2020). Canine distemper virus (CDV) is an RNA virus closely related to measles virus, infecting a wide range of host species (Martinez-Gutierrez and Ruiz-Saenz, 2016).…”

Section: Central Nervous System Infections Causing Metabolic Imbalance -Borna Disease Virus and Canine Distemper Virusmentioning

confidence: 99%

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

Shinjyo

Kita

2021

Front. Cell. Neurosci.

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Metabolic syndromes are frequently associated with dementia, suggesting that the dysregulation of energy metabolism can increase the risk of neurodegeneration and cognitive impairment. In addition, growing evidence suggests the link between infections and brain disorders, including Alzheimer’s disease. The immune system and energy metabolism are in an intricate relationship. Infection triggers immune responses, which are accompanied by imbalance in cellular and organismal energy metabolism, while metabolic disorders can lead to immune dysregulation and higher infection susceptibility. In the brain, the activities of brain-resident immune cells, including microglia, are associated with their metabolic signatures, which may be affected by central nervous system (CNS) infection. Conversely, metabolic dysregulation can compromise innate immunity in the brain, leading to enhanced CNS infection susceptibility. Thus, infection and metabolic imbalance can be intertwined to each other in the etiology of brain disorders, including dementia. Insulin and leptin play pivotal roles in the regulation of immunometabolism in the CNS and periphery, and dysfunction of these signaling pathways are associated with cognitive impairment. Meanwhile, infectious complications are often comorbid with diabetes and obesity, which are characterized by insulin resistance and leptin signaling deficiency. Examples include human immunodeficiency virus (HIV) infection and periodontal disease caused by an oral pathogen Porphyromonas gingivalis. This review explores potential interactions between infectious agents and insulin and leptin signaling pathways, and discuss possible mechanisms underlying the relationship between infection, metabolic dysregulation, and brain disorders, particularly focusing on the roles of insulin and leptin.

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Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates

Cited by 6 publications

References 162 publications

Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus

Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus

The Pathogenesis of Proventricular Dilatation Disease Caused by Parrot Bornaviruses: A Possible Role For Neuropeptide Y (Npy)

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

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Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates

Cited by 6 publications

References 162 publications

Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus

Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus

The Pathogenesis of Proventricular Dilatation Disease Caused by Parrot Bornaviruses: A Possible&nbsp;Role For Neuropeptide Y (Npy)

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

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The Pathogenesis of Proventricular Dilatation Disease Caused by Parrot Bornaviruses: A Possible Role For Neuropeptide Y (Npy)