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1.
Zool Res ; 44(4): 712-724, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37313848

ABSTRACT

Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.


Subject(s)
Brain Diseases , Cognitive Dysfunction , Delirium , Animals , Mice , Scopolamine/toxicity , Brain Diseases/veterinary , Brain , Cognitive Dysfunction/chemically induced , Delirium/chemically induced
2.
Eur J Neurosci ; 44(5): 2247-57, 2016 09.
Article in English | MEDLINE | ID: mdl-27336845

ABSTRACT

Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease.


Subject(s)
Action Potentials , Globus Pallidus/metabolism , Neurons/physiology , Orexins/metabolism , Parkinson Disease/metabolism , Animals , Benzoxazoles/pharmacology , Globus Pallidus/cytology , Globus Pallidus/physiology , Haloperidol/pharmacology , Male , Naphthyridines , Neurons/drug effects , Neurons/metabolism , Orexin Receptor Antagonists/pharmacology , Orexin Receptors/metabolism , Orexins/pharmacology , Oxidopamine/toxicity , Parkinson Disease/etiology , Parkinson Disease/physiopathology , Postural Balance , Rats , Rats, Wistar , Urea/analogs & derivatives , Urea/pharmacology
3.
Peptides ; 66: 1-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25698232

ABSTRACT

Previous studies have shown that secretin and secretin receptors are expressed in central amygdala neurons. By using both in vivo extracellular recording as well as behavioral test, we investigated the direct electrophysiological effects of secretin in the central amygdala and its involvement in feeding behavior. Micro-pressure ejection of secretin increased the spontaneous firing rate by 104.22±26.18% in 13 out of the 27 central amygdala neurons. In other 6 out of the 27 neurons, secretin decreased the firing rate by 68.80±12.10%. Firing patter analysis showed that secretin did not change the firing pattern significantly. Further electrophysiological recordings revealed that secretin decreased the firing rate of glucose-sensitive neurons. In behavioral test, microinjection of secretin into the central amygdala significantly reduced cumulative food intake through cAMP-activated protein kinase activation. Based on the present electrophysiological and behavioral findings, we hypothesized that secretin may suppress food intake by its modulation of spontaneous firing of central amygdala neurons.


Subject(s)
Central Amygdaloid Nucleus/drug effects , Central Amygdaloid Nucleus/metabolism , Feeding Behavior/drug effects , Neurons/drug effects , Neurons/metabolism , Secretin/pharmacology , Action Potentials/drug effects , Animals , Electrophysiology , Male , Rats , Rats, Wistar
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