Areca nut is the basic ingredient of betel quid,which is chewed by hundreds of millions of people in South-Eastern Asia.Chewing of areca nut has been associated with oral cancers potentially due to its specific alkalo...Areca nut is the basic ingredient of betel quid,which is chewed by hundreds of millions of people in South-Eastern Asia.Chewing of areca nut has been associated with oral cancers potentially due to its specific alkaloids,among which arecoline constitutes about 90%of total fraction.Being the world’s fourth most commonly used psychoactive substance,arecoline evokes stimulation,addiction,and other direct neurological effects,while its misuse correlates to neurotoxic effects.However,what might underlie its neurotoxic mechanisms has been poorly documented.The brain is encoded by a complex network of neuronal and glial cell types,and neurotoxicity of hazardous compounds present transcriptional heterogeneity.Recently,the eusocial bumblebee has been used as a model for studying brain effects,with sophisticated cognitive capability and precisely measured brain architecture.Here,we decipher cell-type-specific mental risks to arecoline using bumblebees.Arecoline induced locomotor hyperactivity and cognitive impairment.Single nucleus RNA sequencing(snRNA-seq)unearthed arecoline-induced cell-specific responses,primarily targeted on Kenyon cells(KC).Moreover,high-dose arecoline induced distinctive cell responses among KC subtypes,particularly class I large Kenyon cell(lKC),leading to DNA damage,excitatory/inhibitory(E/I)imbalance,and calcium dyshomeostasis,which potentially resulted in cognitive impairment.Given arecoline’s popularity and growing exposure risks to humans,neurological health risks of areca nut warrant serious consideration.展开更多
Acrylamide(AA)is a common carcinogen that affects the development and function of the central nervous system(CNS).At present,the toxic injuries of common AA are mainly divided into acute and chronic attacks,and the da...Acrylamide(AA)is a common carcinogen that affects the development and function of the central nervous system(CNS).At present,the toxic injuries of common AA are mainly divided into acute and chronic attacks,and the damage caused to the CNS is different.To investigate whether different doses of AA have different effects on brain cells,we performed single-nucleus RNA sequencing of the brain.The findings indicated that short-term high-dose(acute)AA directly disrupted protein synthesis and protein structure stability on the endoplasmic reticulum.Additionally,acute AA was observed to downregulate genes that inhibit apoptosis and autophagy,promote apoptosis,accelerate cell aging,and affect cell function in glial cells(Glia).Longterm low-dose(chronic)AA exposure elevated Ca^(2+)concentration,increased protein autophosphorylation,and induced mitochondrial dysfunction,resulting in impaired axonal transport and disrupted metabolism of Kenyon cells(KCs).These findings highlight the cell type-specific effects of AA,where acute exposure disrupts Glia protein homeostasis,and chronic exposure impairs calcium signaling and axonal transport in KCs.Such results deepen our understanding of AA-induced neurotoxicity and lay the groundwork for developing targeted therapeutic strategies to mitigate its effects on the CNS.展开更多
基金supported by the National Natural Science Foundation of China Project(32200387)the Emergency Project for Risk Assessment of Areca Nut(Key Project of the Department of Agriculture and Rural Affairs of Hainan Province&Wanning Municipal People’s Government).
文摘Areca nut is the basic ingredient of betel quid,which is chewed by hundreds of millions of people in South-Eastern Asia.Chewing of areca nut has been associated with oral cancers potentially due to its specific alkaloids,among which arecoline constitutes about 90%of total fraction.Being the world’s fourth most commonly used psychoactive substance,arecoline evokes stimulation,addiction,and other direct neurological effects,while its misuse correlates to neurotoxic effects.However,what might underlie its neurotoxic mechanisms has been poorly documented.The brain is encoded by a complex network of neuronal and glial cell types,and neurotoxicity of hazardous compounds present transcriptional heterogeneity.Recently,the eusocial bumblebee has been used as a model for studying brain effects,with sophisticated cognitive capability and precisely measured brain architecture.Here,we decipher cell-type-specific mental risks to arecoline using bumblebees.Arecoline induced locomotor hyperactivity and cognitive impairment.Single nucleus RNA sequencing(snRNA-seq)unearthed arecoline-induced cell-specific responses,primarily targeted on Kenyon cells(KC).Moreover,high-dose arecoline induced distinctive cell responses among KC subtypes,particularly class I large Kenyon cell(lKC),leading to DNA damage,excitatory/inhibitory(E/I)imbalance,and calcium dyshomeostasis,which potentially resulted in cognitive impairment.Given arecoline’s popularity and growing exposure risks to humans,neurological health risks of areca nut warrant serious consideration.
基金supported by the National Natural Science Foundation of China Project(32230081).
文摘Acrylamide(AA)is a common carcinogen that affects the development and function of the central nervous system(CNS).At present,the toxic injuries of common AA are mainly divided into acute and chronic attacks,and the damage caused to the CNS is different.To investigate whether different doses of AA have different effects on brain cells,we performed single-nucleus RNA sequencing of the brain.The findings indicated that short-term high-dose(acute)AA directly disrupted protein synthesis and protein structure stability on the endoplasmic reticulum.Additionally,acute AA was observed to downregulate genes that inhibit apoptosis and autophagy,promote apoptosis,accelerate cell aging,and affect cell function in glial cells(Glia).Longterm low-dose(chronic)AA exposure elevated Ca^(2+)concentration,increased protein autophosphorylation,and induced mitochondrial dysfunction,resulting in impaired axonal transport and disrupted metabolism of Kenyon cells(KCs).These findings highlight the cell type-specific effects of AA,where acute exposure disrupts Glia protein homeostasis,and chronic exposure impairs calcium signaling and axonal transport in KCs.Such results deepen our understanding of AA-induced neurotoxicity and lay the groundwork for developing targeted therapeutic strategies to mitigate its effects on the CNS.
