Neuroscience
-
Alpha-Synuclein (α-Syn) is expressed in the central nervous system and the nervous system of the gut (enteric nervous system, ENS), and is well known to be the major constituent of Lewy bodies which are the hallmark of Parkinson's disease. Gastrointestinal disorders frequently manifest several years before motor deficits develop in Parkinson's patients. ⋯ We found that α-Syn is predominantly expressed in cholinergic varicosities, which contain vesicular acetylcholine transporter. α-Syn KO mice had higher enteric neuron density and a larger proportion of cholinergic neurons, notably those containing calretinin, demonstrating a role for α-Syn in regulating development of these neurons. Moreover, α-Syn deletion enhanced the amplitude of synaptically activated [Ca2+]i transients that are primarily mediated by acetylcholine activating nicotinic receptors suggesting that α-Syn modulates the availability of acetylcholine in enteric nerve terminals.
-
Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. ⋯ In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration.
-
Sensitivity and reliability of animal behavioral assessment methods are critical for successful translation of in vitro findings to in vivo. Here we report a data transformation process in the elevated open platform task that generates a novel parameter, namely peak tolerance of fear (PTF) or its inversely correlated equivalent of anxiety quotient (AQ), to measure anxiogenic tendency in rodent. As compared to traditional parameters such as travel distance, time, or entries, PTF or AQ displays largely reduced data dispersion not only ingroup but also cross-study and cross-cohort, therefore representing a significant improvement of the methodology for rodent anxiety assessment.
-
Difficulty understanding speech-in-noise (SIN) is a pervasive problem faced by older adults particularly those with hearing loss. Previous studies have identified structural and functional changes in the brain that contribute to older adults' speech perception difficulties. Yet, many of these studies use neuroimaging techniques that evaluate only gross activation in isolated brain regions. ⋯ Additionally, we found top-down β connectivity between prefrontal and auditory cortices strengthened with poorer hearing thresholds despite minimal behavioral differences. This is consistent with the proposal that linguistic brain areas may be recruited to compensate for impoverished auditory inputs through increased top-down predictions to assist SIN perception. Overall, these results emphasize the importance of top-down signaling in low-frequency brain rhythms that help compensate for hearing-related declines and facilitate efficient SIN processing.
-
Synaptosomal-associated protein 25 (SNAP-25) plays an important role in neuropathic pain. However, the underlying mechanism is largely unknown. Vesicular glutamate transporter 2 (VGluT2) is an isoform of vesicular glutamate transporters that controls the storage and release of glutamate. ⋯ In pheochromocytoma (PC12) cells, the expression of VGluT2 was also depended on SNAP-25 dysregulation. Moreover, we found VGluT2 was involved in SNAP-25-mediated regulation of astrocyte expression and activation of the PKA/p-CREB pathway mediated the upregulation of SNAP-25 in neuropathic pain. The findings of our study indicate that VGluT2 contributes to the effect of SNAP-25 in maintaining the development of neuropathic pain and suggests a novel mechanism underlying SNAP-25 regulation of neuropathic pain.