Experimental neurology
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Experimental neurology · Oct 2016
Transient loss of consciousness during hypercapnia and hypoxia: Involvement of pathways associated with general anesthesia.
Transient loss of consciousness (TLOC), frequently triggered by perturbation in essential physiological parameters such as pCO2 or O2, is considered a passive consequence of generalized degradation in high-level cerebral functioning. However, the fact that it is almost always accompanied by atonia and loss of spinal nocifensive reflexes suggests that it might actually be part of a "syndrome" mediated by neural circuitry, and ultimately be adaptive. Widespread suppression by molecules distributed in the vasculature is also the classical explanation of general anesthesia. ⋯ The results implicate neurons in a specific common-core region of the MPTA in TLOC induced by both forms of asphyxia. This is the same area responsible for general anesthesia induced by GABAergic anesthetic agents. This implies the involvement of a common set of brain nuclei and dedicated axonal pathways, rather than nonspecific global suppression, in the mechanism mediating all three instances of TLOC.
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Experimental neurology · Sep 2016
Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons.
To determine the influence of the sonic hedgehog (shh) pathway and its receptor smoothened (smo), on the survival and functionality of dopaminergic (DA) neurons. ⋯ Our study showed the smo receptor function is not required for the maturation and survival of DA neurons during late development, aging or under stress challenge. However, smo function has an influence on behavior in young adult mice and in responses of mice to a drug that modulates DA neurochemistry through regulation of gene expression in DA neurons. Since young adult DAT-smo ko mice show hyperactivity and altered response to a psychostimulant drug (METH), this may indicate the involvement of the shh pathway in the development of functional changes that manifest as alterations in DA pathway dynamics.
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Experimental neurology · Sep 2016
Lack of CAR impacts neuronal function and cerebrovascular integrity in vivo.
Nuclear receptors (NRs) are a group of transcription factors emerging as players in normal and pathological CNS development. Clinically, an association between the constitutive androstane NR (CAR) and cognitive impairment was proposed, however never experimentally investigated. We wished to test the hypothesis that the impact of CAR on neurophysiology and behavior is underlined by cerebrovascular-neuronal modifications. ⋯ Our results indicate that behavioral and electroencephalographic changes in adult CAR(-/-) mice are concomitant to discrete developmental or structural brain defects. The latter could increase the vulnerability to neurotoxins. The possibility that interfering with nuclear receptors during development could contribute to adulthood brain changes is proposed.
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Experimental neurology · Sep 2016
Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy.
Synucleinopathy is characterized by abnormal accumulation of misfolded α-synuclein (α-Syn)-positive cytoplasmic inclusions and by neurodegeneration and cognitive impairments, but the pathogenesis mechanism of synucleinopathy remains to be defined. Using a transmission model of synucleinopathy by intracerebral injection of preformed A53T α-Syn fibrils, we investigated whether aberrant adenosine A2A receptor (A2AR) signaling contributed to pathogenesis of synucleinopathy. ⋯ These findings define α-Syn-triggered aberrant A2AR signaling as a critical pathogenesis mechanism of synucleinopathy with dual controls of cognition and neurodegeneration by modulating α-Syn aggregates. Thus, aberrant A2AR signaling represents a useful biomarker as well as a therapeutic target of synucleinopathy.
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Experimental neurology · Sep 2016
Subthalamic deep brain stimulation alters neuronal firing in canonical pain nuclei in a 6-hydroxydopamine lesioned rat model of Parkinson's disease.
Chronic pain is one of the most common non-motor symptoms of Parkinson's disease (PD) affecting up to 85% of patients. Previous studies have established that reduced mechanical and thermal thresholds occur in both idiopathic PD patients and animal models of PD, suggesting that changes may occur in sensory processing circuits. Improvements in sensory thresholds are achieved using subthalamic nucleus (STN) deep brain stimulation (DBS), however the mechanism by which this occurs remains unresolved. ⋯ Our results suggest that STN DBS alters neuronal firing in descending pain circuits. We hypothesize that STN DBS attenuates excitatory projections from the ACC to the PAG in 6OHDA lesioned rats. Following this, neurons in the PAG respond by either increasing (during HFS only) or decreasing (during both LFS and HFS), which may modulate descending facilitation or inhibition at the level of the spinal cord. Future work should address specific neuronal changes in the ACC and PAG that occur in a freely moving parkinsonian animal during a pain stimulus treated with STN DBS.