Nicotine Regulates Activity Of Lateral Habenula Neurons Via Presynaptic And Postsynaptic Mechanisms

There is much interest in brain regions that drive nicotine intake in smokers. Interestingly, both the rewarding and aversive effects of nicotine are probably critical for sustaining nicotine addiction. The medial and lateral habenular (LHb) nuclei play important roles in processing aversion, and recent work has focused on the critical involvement of the LHb in encoding and responding to aversive stimuli. Several neurotransmitter systems are implicated in nicotine\u27s actions, but very little is known about how nicotinic acetylcholine receptors (nAChRs) regulate LHb activity. Here we report in brain slices that activation of nAChRs depolarizes LHb cells and robustly increases firing, and also potentiates glutamate release in LHb. These effects were blocked by selective antagonists of α6-containing (α6∗) nAChRs, and were absent in α6∗-nAChR knockout mice. In addition, nicotine activates GABAergic inputs to LHb via α4β2-nAChRs, at lower concentrations but with more rapid desensitization relative to α6∗-nAChRs. These results demonstrate the existence of diverse functional nAChR subtypes at presynaptic and postsynaptic sites in LHb, through which nicotine could facilitate or inhibit LHb neuronal activity and thus contribute to nicotine aversion or reward

Pathophysiology and Neuroimmune Interactions Underlying Parkinson’s Disease and Traumatic Brain Injury

Parkinson’s disease (PD) is a progressive neurodegenerative disorder clinically defined by motor instability, bradykinesia, and resting tremors. The clinical symptomatology is seen alongside pathologic changes, most notably the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of α-synuclein and neuromelanin aggregates throughout numerous neural circuits. Traumatic brain injury (TBI) has been implicated as a risk factor for developing various neurodegenerative diseases, with the most compelling argument for the development of PD. Dopaminergic abnormalities, the accumulation of α-synuclein, and disruptions in neural homeostatic mechanisms, including but not limited to the release of pro-inflammatory mediators and the production of reactive oxygen species (ROS), are all present following TBI and are closely related to the pathologic changes seen in PD. Neuronal iron accumulation is discernable in degenerative and injured brain states, as is aquaporin-4 (APQ4). APQ4 is an essential mediator of synaptic plasticity in PD and regulates edematous states in the brain after TBI. Whether the cellular and parenchymal changes seen post-TBI directly cause neurodegenerative diseases such as PD is a point of considerable interest and debate; this review explores the vast array of neuroimmunological interactions and subsequent analogous changes that occur in TBI and PD. There is significant interest in exploring the validity of the relationship between TBI and PD, which is a focus of this review

Additional file 1 of Erbin protects against sepsis-associated encephalopathy by attenuating microglia pyroptosis via IRE1α/Xbp1s-Ca2+ axis

Additional file 1. Fig. S1. Erbin deficiency facilitates NLRP3 inflammasome activation and pyroptosis of microglia in vivo and vitro. Fig. S2. Erbin regulates pyroptosis via IRE1α/Xbp1s/Ca2+ in vivo and vitro. Fig. S3. Erbin inhibits pyroptosis via IRE1α/Xbp1s/Ca2+ in BV2 cells and improves synaptic proteins by inhibiting IRE1α/Xbp1s pathway. Fig. S4. LPS/nigericin stimulation resulted in decreased TXNIP protein levels regardless of Erbin knockdown in BV2 cells