Biology subjects

Khani, A.

Publications and source records attributed to Khani, A..

3 recordsLinked to original sources

bioRxiv2025

Neurovascular Large artery dilatation increases the risk for Alzheimer's disease pathology

Alzheimers disease (AD) and related dementia cases are increasing globally, emphasizing the urgent need to clarify disease mechanisms for translational application in diagnoses and treatment. Vascular alterations represent a major pathological feature of AD, and beyond the well-established roles of small vessel disease and large artery atherosclerosis, our group has previously demonstrated that brain large artery dilatation is associated with elevated risk of dementia and Alzheimer pathology. The most severe manifestation of this non-atherosclerotic arterial phenotype is dolichoectasia, an enlargement of large blood vessels (Gutierrez et al., 2019; Melgarejo et al., 2024). Despite consistent epidemiological evidence across populations, the mechanistic link between arterial dilatation and AD remains poorly understood. To address this gap, we induced dolichoectasia in AppNL-G-F mice, a model of amyloid pathology, by injecting elastase into the cisterna magna. After three months, brains were examined using biochemical and immunohistochemical methods. Elastase-treated mice exhibited a significant increase in amyloid plaques in the hippocampus (p = 0.021) and cortex (p = 0.029) compared with vehicle-treated controls. Neuronal loss was evident in the CA1 region of the hippocampus (p = 0.036), with a trend towards neurodegeneration in CA3 (p = 0.055). We also observed elevated p62 in the hippocampus and cortex (p = 0.009 and p = 0.001, respectively), suggesting impaired protein or autophagic-lysosomal clearance. Although no overt increase in neuroinflammation or astrogliosis was detected at this time point, matrix metalloproteinase-9 (MMP-9) levels were trending towards elevated levels (p = 0.058). Combined, these findings indicate successful elastase-induced brain arterial dilatation accelerates AD-related pathology in AppNL-G-F mice, providing mechanistic evidence that large artery dilatation may contribute directly to Alzheimers disease progression.

neuroscience↗

bioRxiv2020

Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency

Neuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the mitochondrial pyruvate carrier, specifically in adult glutamatergic neurons. We found that, despite decreased levels of oxidative phosphorylation in these excitatory neurons, mice were normal at rest. Paradoxically, in response to mild inhibition of GABA mediated synaptic activity, they rapidly developed severe seizures and died, whereas under similar conditions the behaviour of control mice remained unchanged. We show that neurons with a deficient MPC are intrinsically hyperexcitable as a consequence of impaired calcium homeostasis, which reduces M-type potassium channel activity. Provision of ketone bodies restores energy status, calcium homeostasis and M-channel activity and attenuates seizures in animals fed a ketogenic diet. Our results provide an explanation for the paradoxical seizures that frequently accompany a large number of neuropathologies, including cerebral ischemia and diverse mitochondriopathies, in which neurons experience an energy deficit. One Sentence SummaryDecreased OXPHOS and Ca2+-mediated neuronal hyperexcitability lead to seizure in a mouse model of mitochondrial pyruvate import deficiency.

neuroscience↗

bioRxiv2020

Developing snakebite risk model using venomous snake habitat suitability as an indicating factor: An application of species distribution models in public health research

Snakebite envenoming is an important public health problem in Iran, despite its risk not being quantified. This study aims to use venomous snakes habitat suitability as an indicator of snakebite risk, to identify high-priority areas for snakebite management across the country. Thus, an ensemble approach using five distribution modeling methods: Generalized Boosted Models, Generalized Additive Models, Maximum Entropy Modeling Generalized Linear Models, and Random Forest was applied to produce a spatial snakebite risk model for Iran. To achieve this, four venomous snakes habitat suitability (Macrovipera lebetina, Echis carinatus, Pseudocerastes persicus and Naja oxiana) were modeled and then multiplied. These medically important snakes are responsible for the most snakebite incidents in Iran. Multiplying habitat suitability models of the four snakes showed that the northeast of Iran (west of Khorasan-e-Razavi province) has the highest snakebite risk in the country. In addition, villages that were at risk of envenoming from the four snakes were identified. Results revealed that 51,112 villages are at risk of envenoming from M. lebetina, 30,339 from E. carinatus, 51,657 from P. persicus and 12,124 from N. oxiana. This paper demonstrates application of species distribution modeling in public health research and identified potential snakebite risk areas in Iran by using venomous snakes habitat suitability models as an indicating factor. Results of this study can be used in snakebite and human-snake conflict management in Iran. We recommend increasing public awareness of snakebite envenoming and education of local people in areas which identified with the highest snakebite risk.

ecology↗