ABSTRACT
The raphe nuclei comprise nearly all of 5-hydroxytryptaminergic (5-HTergic) neurons in the brain and are widely acknowledged to participate in the modulation of neural excitability. "Excitability-inhibition imbalance" results in a variety of brain disorders, including epilepsy. Epilepsy is a common neurological disorder characterized by hypersynchronous epileptic seizures accompanied by many psychological, social, cognitive consequences. Current antiepileptic drugs and other therapeutics are not ideal to control epilepsy and its comorbidities. Cumulative evidence suggests that the raphe nuclei and 5-HTergic system play an important role in epilepsy and epilepsy-associated comorbidities. Seizure activities propagate to the raphe nuclei and induce various alterations in different subregions of the raphe nuclei at the cellular and molecular levels. Intervention of the activity of raphe nuclei and raphe 5-HTergic system with pharmacological or genetic approaches, deep brain stimulation or optogenetics produces indeed diverse and even contradictory effects on seizure and epilepsy-associated comorbidities in different epilepsy models. Nevertheless, there are still many open questions left, especially regarding to the relationship between 5-HTergic neural circuit and epilepsy. Understanding of 5-HTergic network in a circuit- and molecule-specific way may not only be therapeutically relevant for increasing the drug specificity and precise treatment in epilepsy, but also provide critical hints for other brain disorders with abnormal neural excitability. In this review we focus on the roles of the raphe 5-HTergic system in epilepsy and epilepsy-associated comorbidities. Besides, further perspectives about the complexity and diversity of the raphe nuclei in epilepsy are also addressed.
Subject(s)
Epilepsy , Raphe Nuclei , Humans , Brain , Seizures , NeuronsABSTRACT
AIMS: Pharmaco-genetics emerges as a new promising approach for epileptic seizures. Whether it can modulate epileptogenesis is still unknown. METHODS: Here, parvalbumin neurons and pyramidal neurons of the seizure focus were transfected with engineered excitatory Gq-coupled human muscarinic receptor hM3Dq and engineered inhibitory Gi-coupled human muscarinic receptor hM4Di, respectively. And their therapeutic value in mouse hippocampal kindling-induced epileptogenesis was tested. RESULTS: Pharmaco-genetic activating parvalbumin neurons limitedly retarded the progression of behavioral seizure stage and afterdischarge duration (ADD) during epileptogenesis induced by kindling. Activating parvalbumin neurons delayed seizure development only in the early stage, but accelerated it in late stages. On the contrary, pharmaco-genetic inhibiting pyramidal neurons robustly retarded the progression of seizure stages and ADDs, which greatly delayed seizure development in both early and late stages. Although both pharmaco-genetic therapeutics efficiently alleviated the severity of acute kindling-induced seizures, pharmaco-genetic inhibiting pyramidal neurons were able to reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco-genetic activating parvalbumin neurons. CONCLUSION: Our results demonstrated that pharmaco-genetic inhibiting pyramidal neurons retard hippocampal kindling-induced epileptogenesis and reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco-genetic activating parvalbumin neurons. It suggests that pharmaco-genetics targeting pyramidal neurons may be a promising treatment for epileptogenesis.
Subject(s)
Anticonvulsants/administration & dosage , Hippocampus/physiology , Kindling, Neurologic/physiology , Protein Engineering/methods , Pyramidal Cells/physiology , Seizures/prevention & control , Animals , Combined Modality Therapy/methods , Hippocampus/drug effects , Kindling, Neurologic/drug effects , Male , Mice , Mice, Transgenic , Pyramidal Cells/drug effects , Receptors, Muscarinic/genetics , Receptors, Muscarinic/metabolism , Seizures/genetics , Seizures/physiopathologyABSTRACT
Car for transporting passenger is the most common means of transport and in-car airborne volatile organic compounds (VOCs) cause harm to health. In order to analyze the pollution levels of benzene, toluene, ethylbenzene, xylenes, styrene and TVOC, index evaluation method was used according to the domestic and international standards of indoor and in-car air quality (IAQ). For Chinese GB/T 18883-2002 IAQ Standard, GB/T 17729-2009 Hygienic Standard for the Air Quality inside Long Distance Coach, GB/T 27630-2011 Guideline for Air Quality Assessment of Passenger Car, IAQ standard of South Korea, Norway, Japan and Germany, the heaviest pollution of VOCs in passenger car was TVOC, TVOC, benzene, benzene, TVOC, toluene and TVOC, respectively, the average pollution grade of automotive IAQ was median pollution, median pollution, clean, light pollution, median pollution, clean and heavy pollution, respectively. Index evaluation can effectively analyze vehicular interior air quality, and the result has a significant difference with different standards; German standard is the most stringent, while Chinese GB/T 18883-2002 standard is the relatively stringent and GB/T 27630-2011 is the most relaxed.
